bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental influences on symptom expression in antipsychotic-naïve first-episode psychosis
Authors: Bridgwater Miranda , Bachman Peter , Tervo-Clemmens Brenden , Haas Gretchen , Hayes Rebecca , Luna Beatriz , Salisbury Dean F. , Jalbrzikowski Maria
Published: October 2020

Background

The neurodevelopmental model of psychosis was established over 30 years ago; however, the developmental influence on psychotic symptom expression – how age affects clinical presentation in first-episode psychosis – has not been thoroughly investigated.

Methods

Using generalized additive modeling, which allows for linear and non-linear functional forms of age-related change, we leveraged symptom data from a large sample of antipsychotic-naïve individuals with first-episode psychosis (N= 340, 12–40 years, 1–12 visits), collected at the University of Pittsburgh from 1990 to 2017. We examined relationships between age and severity of perceptual and non-perceptual positive symptoms and negative symptoms. We tested for age-associated effects onchangein positive or negative symptom severity following baseline assessment and explored the time-varying relationship between perceptual and non-perceptual positive symptoms across adolescent development.

Results

Perceptual positive symptom severity significantly decreased with increasing age (F= 7.0,p= 0.0007;q= 0.003) while non-perceptual positive symptom severity increased with age (F= 4.1,p= 0.01,q= 0.02). Anhedonia severity increased with increasing age (F= 6.7,p= 0.00035;q= 0.0003), while flat affect decreased in severity with increased age (F= 9.8,p= 0.002;q= 0.006). Findings remained significant when parental SES, IQ, and illness duration were included as covariates. There were no developmental effects on change in positive or negative symptom severity (allp> 0.25). Beginning at age 18, there was a statistically significant association between severity of non-perceptual and perceptual symptoms. This relationship increased in strength throughout adulthood.

Conclusions

These findings suggest that as maturation proceeds, perceptual symptoms attenuate while non-perceptual symptoms are enhanced. Findings underscore how pathological brain–behavior relationships vary as a function of development.
Dosimetric comparison of volumetric-modulated arc therapy and helical tomotherapy for adjuvant treatment of bilateral breast cancer
Authors: Phurailatpam Reena , Wadasadawala Tabassum , Chauhan Kamalnayan , Panda Subhajit , Sarin Rajiv
Published: October 2020

Purpose:

Dosimetric comparison between volumetric-modulated arc therapy (VMAT) and helical tomotherapy (HT) in the treatment of bilateral breast cancer (BBC).

Materials and methods:

Ten patients treated on HT were selected retrospectively. Dose prescription was 50 Gy in 25 fractions to breast/chest wall and supraclavicular fossa (SCF) while tumour bed was simultaneously boosted to 61 Gy in 25 fractions. VMAT plans were made with four mono-isocentric partial arcs. The monitoring unit (MU) and treatment time were used to quantify the treatment efficiency. Target volumes were compared for homogeneity index (HI), conformity index (CI) while organs at risk (OARs) were compared for relevant dose volumes and integral doses (IDs).

Result:

For targets, no significant difference is observed between VMAT and HT in CI but VMAT could give better HI. The mean lung dose,V20andV5is 10·6 Gy versus 8·4 Gy (p-value 0·03), 12% versus 11·5% (p-value 0·5) and 78·1% versus 43·4% (p-value 0·005), respectively. The mean heart dose,V30andV5is 4·9 Gy versus 4·7 Gy (p-value 0·88), 0·5% versus 1·5% (p-value 0·18) and 26·2% versus 22·8% (p-value 0·4). Integral dose (ID) for the whole body and heart are comparable: 289 Gy kg versus 299 Gy kg (p-value 0·24) and 2·9 Gy kg versus 2·8 Gy kg (p-value 0·80). ID for lungs was significantly higher with VMAT: 7·9 Gy kg versus 6·3 Gy kg (p-value 0·03). There is a 53% reduction in treatment time and 78% in MU with VMAT against HT.

Conclusion:

VMAT can generate clinically acceptable plans comparable to HT for BBC. HT shows better control over low dose spillage in lungs compared to VMAT thereby increasing ID to lungs. VMAT shows better homogeneity and efficient treatment delivery than HT.
Dosimetric comparison of 3-dimensional conformal radiotherapy (3D-CRT) and volumetric-modulated arc therapy (VMAT) in locally advanced cancer cervix
Authors: Agrawal Animesh , Hadi Rahat , Rath Satyajeet , Bharati Avinav , Rastogi Madhup , Khurana Rohini , Sahni Kamal , Sapru Shantanu , Gandhi Ajeet Kumar , Srivastava Anoop Kumar , Mishra Surendra Prasad
Published: October 2020

Introduction:

Dosimetric advantages of volumetric-modulated arc therapy (VMAT) over three-dimensional conformal radiotherapy (3D-CRT) are not established in a head-on comparison of a uniform group of locally advanced carcinoma of the cervix (LACC). Therefore, we conducted a dosimetric comparison of these two techniques in LACC patients.

Materials and methods:

Computed tomography (CT) data of histologically proven de novo LACC, including Stage IIB–IIIB and earlier stages deemed inoperable, were included in this prospective observational dosimetric study. Planning was initially done by 3D-CRT technique (dose of 45–50·4 Gy @ 1·8–2 Gy/# was used in the actual treatment), followed by VMAT planning and appropriate dosimetric comparisons were done in 39 cases.

Results:

For planning target volume coverage, D95, D98 and D100 (p < 0·0001 for all parameters) and V95 and V100 (p = 0·002 and <0·0001, respectively) were significantly improved with VMAT. The conformity index (CI) was significantly better with VMAT (p = 0·03), while 3D-CRT had a significantly better homogeneity index (HI)(p = 0·003). Dose to the urinary bladder was significantly reduced with VMAT compared to 3D-CRT for V20–V50, except V10. The doses to the rectum and abdominal cavity were significantly reduced with VMAT compared to 3D-CRT plans for all parameters (V10–V50). The number of organs at risks (OARs) for which constraints were met was higher with VMAT plans than with 3D-CRT plans, with at least four out of the five OARs protected in 46·1 versus 5·1% and all constraints achieved in 15·4% versus none.

Conclusion:

We conclude that in dosimetric terms, VMAT is superior to 3D-CRT for LACC.
Expecting the unexpected in the search for extraterrestrial life
Authors: Vickers Peter
Published: October 2020

On p. 10 of the 2018 National Academies Exoplanet Science Strategy document (NASEM 2018), ‘Expect the unexpected’ is described as a general principle of the exoplanet field. But for the next 150 pages, this principle is apparently forgotten, as strategy decisions are repeatedly put forward based on our expectations. This paper explores what exactly it might mean to ‘expect the unexpected’, and how this could possibly be achieved by the space science community. An analogy with financial investment strategies is considered, where a balanced portfolio of low/medium/high-risk investments is recommended. Whilst this kind of strategy would certainly be advisable in many scientific contexts (past and present), in certain contexts – especially exploratory science – a significant disanalogy needs to be factored in: financial investors cannot choose low-risk high-reward investments, but sometimes scientists can. The existence of low-risk high-impact projects in cutting-edge space science significantly reduces the warrant for investing in high-risk projects, at least in the short term. However, high-risk proposals need to be fairly judged alongside medium- and low-risk proposals, factoring in both the degree of possible reward and the expected cost of the project. Attitudes towards high-risk high-impact projects within NASA since 2009 are critically analysed.
On Random and Systematic Variation in the Prevalence of Defective Color Vision
Authors: Stark Alan E.
Published: October 2020

Defective color vision comes in various forms and its frequency varies from population to population. This article is concerned with only the sex-linked form of essential hereditary color blindness. A model of a ‘small’ population is constructed to explore the dynamics of occurrence of color blindness. Different mutation rates are introduced for eggs and sperm. Birth and death rates of affected individuals are assumed to be the same as those in the unaffected. Simulation demonstrates that large changes in frequency occur randomly from the combined effects of mutation, transmission of genes from generation to generation and births and deaths. A reference is made to the hypothesis that observed differences in rates are due to selection in the transition from hunter-gatherer to farmer.
A New Mechanism for Submarine Groundwater Discharge From Continental Shelves
Authors: George Camaron , Moore Willard S. , White Scott M. , Smoak Erin , Joye Samantha B. , Leier Andrew , Wilson Alicia M.
Published: October 2020

Marine tracer studies indicate that large volumes of saline groundwater discharge to the ocean in passive margin settings. These results have not found widespread recognition because the location and cause(s) of this submarine groundwater discharge (SGD) are unclear. Here we report observations from a new long‐term seafloor monitoring network in the South Atlantic Bight that support large‐scale SGD far from shore. In the study area near Charleston, South Carolina, we determined hydrostratigraphy via vibracoring and chirp seismic surveys, collected water samples from seafloor wells, and used heat as a tracer to monitor SGD. We detected significant pulses of saline SGD issuing from the seafloor 10–15 km from shore. These pulses coincided with abrupt sea level declines of up to 30 cm. Based on an analysis of marine conditions at the time, we propose that upwelling‐favorable winds depressed sea level in the region, causing saline groundwater to discharge from confined coastal aquifers that connect land and ocean. The combination of stacked confined aquifers and variations in sea level are nearly ubiquitous in passive coastal margins. This previously overlooked combination can explain a wide range of other published observations and promotes more dynamic flows than simple tidal fluctuations. This new mechanism may explain Ra tracer signals in the coastal Atlantic Ocean and supports significant nutrient inputs to the ocean. These large natural geochemical fluxes may be sensitive to groundwater usage on land.
Legacy Effects from Historical Environmental Changes Dominate Future Terrestrial Carbon Uptake
Authors: Krause A. , Arneth A. , Anthoni P. , Rammig A.
Published: October 2020

Ecosystems continuously adapt to interacting environmental drivers that change over time. Consequently, the carbon balance of terrestrial ecosystem may presently still be affected by past anthropogenic disturbances (e.g., deforestation) and other environmental changes (e.g., climate change). However, even though such so‐called “legacy effects” are implicitly included in many carbon cycle modeling studies, they are typically not explicitly quantified and therefore scientists might not be aware of their long‐term importance. Here, we use the ecosystem model LPJ‐GUESS to quantify legacy effects for the 21st century and the respective contributions of the following environmental drivers: climate change, CO2 fertilization, land use change, wood harvest, nitrogen deposition, and nitrogen fertilization. According to our simulations, the combined legacy effects of historical (1850–2015) environmental changes result in a land carbon uptake of +126 Gt C over the future (2015–2099) period. This by far exceeds the impacts of future environmental changes (range −53 Gt C to +16 Gt C for three scenarios) and is comparable in magnitude to historical carbon losses (−154 Gt C). Legacy effects can mainly be attributed to ecosystems still adapting to historical increases in atmospheric CO2 (+65 Gt C) and nitrogen deposition (+33 Gt C), but long‐term vegetation regrowth following agricultural abandonment (+8 Gt C) and wood harvest (+19 Gt C) also play a role. The response of the biosphere to historical environmental changes dominates future terrestrial carbon cycling at least until midcentury. Legacy effects persist many decades after environmental changes occurred and need to be considered when interpreting changes and estimating terrestrial carbon uptake potentials.
Estimating Extreme Geoelectric Field Values for the Australian Region
Authors: Marshall Richard , Dziura Léna , Wang Liejun , Young Jeanne , Terkildsen Michael
Published: October 2020

There are a number of global initiatives to understand and mitigate the impacts of extreme space weather on critical infrastructure and modern society. This paper provides the results of an analysis to estimate extreme geoelectric field values for the Australian region to facilitate evaluation of Australia's power system response to extreme geomagnetic storms. Geoelectric fields are calculated using a grid of modeled magnetotelluric impedance tensors obtained from a 3‐D conductivity model of the Australian region. Statistical metrics derived from grids of geoelectric field time series are analyzed as a function of Dst index for different storm days to extrapolate geoelectric fields to extreme storm levels over a range of ground conductivity conditions. For Carrington event storm levels, geoelectric field values of 5.3 ± 3.8 V/km in the north‐south direction and 9.6 ± 4.3 V/km in the east‐west direction are expected for areas of electrically resistive rocks near coastlines that are adjacent to deep highly conductive oceans, and inland, where there are large contrasts between the electrical conductivities of different rock types across Australia. Further, geoelectric field values may change by at least an order of magnitude over the grid spacing interval of 50 km in these areas. The results of the analysis also suggest that upscaling grids of geoelectric field time series derived from an observed storm by the ratio of extreme storm Dst to the observed storm Dst are a valid approach for the Australian region that provides extreme storm scenarios for different storm morphologies.
Deformation Analysis in the Barents Sea in Relation to Paleogene Transpression Along the Greenland‐Eurasia Plate Boundary
Authors: Gac Sébastien , Minakov Alexander , Shephard Grace E. , Faleide Jan Inge , Planke Sverre
Published: October 2020

Late Cretaceous‐Cenozoic contractional structures are widespread in the Barents Sea. While the exact dating of the deformation is unclear, it can only be inferred that the contraction is younger than the early Cretaceous. One likely contractional mechanism is related to Greenland Plate kinematics at Paleogene times. We use a thin sheet finite element modeling approach to compute deformation within the Barents Sea in response to the Greenland‐Eurasia relative motions during the Paleogene. The analytical solution for the 3‐D folding of sediments above basement faults is used to assess possibilities for folding. Two existing Greenland Plate kinematic models, differing slightly in the timing, magnitude, and direction of motion, are tested. Results show that the Greenland Plate's general northward motion promotes growing anticlines in the entire Barents Sea shelf. Our numerical models suggest that the fan‐shaped pattern of cylindrical anticlines in the Barents Sea can be associated with the Eurekan deformation concurrent to the initial rifting and early seafloor spreading in the northeast Atlantic. The main contraction phase in the SW Barents Sea coincides with the timing of continental breakup, whereas the peak of deformation predicted for the NW Barents Sea occurred at later times. Svalbard has experienced a prolonged period of compressional deformation. We conclude that Paleogene Greenland Plate kinematics are a likely candidate to explain contractional structures in the Barents Sea.
From Caledonian Collapse to North Sea Rift: The Extended History of a Metamorphic Core Complex
Authors: Wiest J. D. , Wrona T. , Bauck M. S. , Fossen H. , Gawthorpe R. L. , Osmundsen P. T. , Faleide J. I.
Published: October 2020

Extensional systems evolve through different stages due to changes in the rheological state of the lithosphere. It is crucial to distinguish ductile structures formed before and during rifting, as both cases have important but contrasting bearings on the structural evolution. To address this issue, we present the illustrative ductile‐to‐brittle structural history of a metamorphic core complex (MCC) onshore and offshore western Norway. Combining geological field mapping with newly acquired 3‐D seismic reflection data, we correlate two distinct onshore basement units (BU1 and BU2) to corresponding offshore basement seismic facies (SF1 and SF2). Our interpretation reveals two 40 km wide domes (one onshore and one offshore), which both show characteristic kilometer‐scale, westward plunging upright folds. The gneiss domes fill antiformal culminations in the footwall of a >100 km long, shallowly west dipping, extensional detachment. Overlying Caledonian nappes and Devonian supradetachment basins occupy saddles of the hyperbolic detachment surface. Devonian collapse of the Caledonian orogen formed dome and detachment geometries. During North Sea rifting, brittle reactivation of the MCC resulted in complex fault patterns deviating from N‐S strike dominant at the eastern margin of the rift. Around 61°N, only minor N‐S faults (<100 m throw) cut through the core of the MCC. Major rift faults (≤5 km throw), on the other hand, reactivated the detachment and follow the steep flanks of the MCC. This highlights that inherited ductile structures can locally alter the orientation of brittle faults formed during rifting.
Correction to: Autophagy in bone homeostasis and the onset of osteoporosis
Authors: Yin Xing , Zhou Chenchen , Li Jingtao , Liu Renkai , Shi Bing , Yuan Quan , Zou Shujuan
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A first-in-human phase 1 and pharmacological study of TAS-119, a novel selective Aurora A kinase inhibitor in patients with advanced solid tumours
Authors: Robbrecht Debbie G. J. , Lopez Juanita , Calvo Emiliano , He Xiaomin , Hiroshi Hirai , Soni Nital , Cook Natalie , Dowlati Afshin , Fasolo Angelica , Moreno Victor , Eskens Ferry A. L. M. , de Bono Johann S.
Published: October 2020

Background

This is a first-in-human study with TAS-119, an Aurora A kinase (AurA) inhibitor.

Methods

Patients with advanced, refractory, solid tumours were enrolled into 5 dose escalation cohorts (70–300 mg BID, 4 days on/3 days off, 3 out of 4 weeks or 4 out of 4 weeks). The expansion part consisted of patients with small-cell lung cancer, HER2-negative breast cancer,MYC-amplified/β-catenin-mutated (MT) tumours or other (basket cohort).

Results

In the escalation part (n = 34 patients), dose-limiting toxicities were one grade 3 nausea, two grade 2 and one grade 3 ocular toxicity and a combination of fatigue, ocular toxicity and nausea in one patient (all grade 2) at dose levels of 150, 200, 250 and 300 mg, respectively. Most frequent treatment-related adverse events were fatigue (32%), diarrhoea (24%) and ocular toxicity (24%). Toxicity grade ≥3 in ≥10% of patients were diarrhoea (15%) and increased lipase (12%). The maximum tolerated dose was 250 mg BID. Due to one additional grade 1 ocular toxicity, the RP2D was set at 200 mg BID (4 days on/3 days off, 3 out of 4 weeks), which was further explored in the expansion part (n = 40 patients). Target inhibition in paired skin biopsies was shown.

Conclusions

TAS-119 has a favourable and remarkably distinct safety profile from other AurA inhibitors.

Clinical trial registration

NCT02448589.
Deep sequencing detects human papillomavirus (HPV) in cervical cancers negative for HPV by PCR
Authors: Arroyo Mühr Laila Sara , Lagheden Camilla , Lei Jiayao , Eklund Carina , Nordqvist Kleppe Sara , Sparén Pär , Sundström Karin , Dillner Joakim
Published: October 2020

Background

Human papillomavirus (HPV) is a necessary cause of cervical cancer, although some invasive cervical cancers may test negative by HPV PCR. We previously requested all invasive cervical cancers in Sweden during 10 years and subjected them to PCR. We also optimised methods for deep sequencing of formalin-fixed paraffin-embedded samples.

Methods

Using Novaseq 6000, we simultaneously sequenced total DNA and cDNA from 392 HPV PCR-negative cervical cancers. Non-human reads were queried against all known HPVs. The complete database now contains PCR and/or deep sequencing data on 2850 invasive cervical cancers.

Results

HPV sequences were detected in 169/392 of HPV PCR-negative cervical cancers. Overall, 30 different HPV types were detected, but only 5 types were present in proportions above 3% of cancers. More than 92% of tumours were HPV-positive in PCR and/or sequencing (95% confidence interval: 91.1–93.1%). Exploring possible reasons for failure to previously detect HPV suggest that more sensitive type-specific PCRs for HPV 31, 33, 45 and 73 targeting retained regions of HPV would have detected most of these (117/392).

Conclusions

Unbiased deep sequencing provides comprehensive data on HPV types in cervical cancers and appears to be an important tool for quality assurance of HPV screening.
EFTUD2 maintains the survival of tumor cells and promotes hepatocellular carcinoma progression via the activation of STAT3
Authors: Tu Mengxian , He Lu , You Yang , Li Jinying , Yao Nan , Qu Chen , Huang Wei , Xu Leibo , Luo Rongcheng , Hong Jian
Published: October 2020

Elongation factor Tu GTP binding domain containing 2 (EFTUD2), a spliceosomal GTPase, plays a pivotal role in multiple organ development and innate immune. It has been reported that EFTUD2 is a new host factor with activity against HCV infection. However, the role of EFTUD2 in solid tumors, including hepatocellular carcinoma (HCC), remains unexplored. In this study, we investigated the molecular function of EFTUD2 in HCC. Data from The Cancer Genome Atlas (TCGA) indicated an upregulation of EFTUD2 in HCC tissues compared to that in nontumor liver tissues. Immunohistochemical analysis performed on two independent HCC cohorts confirmed the upregulation of EFTUD2 in HCC tissues and further suggested that a high level of EFTUD2 expression predicted shorter overall and recurrence-free survival in HCC patients. Functional studies suggested that siRNA interference with EFTUD2 expression significantly suppressed cell viability, blocked cell cycle progression, facilitated tumor cell apoptosis, and inhibited metastasis, while the enhancement of EFTUD2 expression promoted the proliferation and migration of HCC cells both in vitro and in vivo. Surprisingly, we also found that the stable knockdown of EFTUD2 expression via lentivirus infection was lethal for HCC cells. This finding suggested that EFTUD2 was essential for maintaining the survival of HCC cells. Mechanistically, RNA sequencing and gene set enrichment analysis (GSEA) suggested that the gene sets of epithelial–mesenchymal transition (EMT) and the JAK/STAT3 pathway were enriched in EFTUD2-overexpressing cells. Further verification indicated that EFTUD2-overexpressing cells exhibited an EMT-like phenotype and had enhanced STAT3 activation, while the STAT3 inhibitor S3I-201 partially blocked these pro-malignant effects of EFTUD2 overexpression. In summary, we report EFTUD2 as a novel oncogene that helps to maintain the survival of HCC cells and promotes HCC progression through the activation of STAT3. The high level of expression of EFTUD2 in HCC tissues indicates shorter overall and recurrence-free survival in HCC patients.
Authentic self-expression on social media is associated with greater subjective well-being
Authors: Bailey Erica R. , Matz Sandra C. , Youyou Wu , Iyengar Sheena S.
Published: October 2020

Social media users face a tension between presenting themselves in an idealized or authentic way. Here, we explore how prioritizing one over the other impacts users’ well-being. We estimate the degree of self-idealized vs. authentic self-expression as the proximity between a user’s self-reported personality and the automated personality judgements made on the basis Facebook Likes and status updates. Analyzing data of 10,560 Facebook users, we find that individuals who are more authentic in their self-expression also report greater Life Satisfaction. This effect appears consistent across different personality profiles, countering the proposition that individuals with socially desirable personalities benefit from authentic self-expression more than others. We extend this finding in a pre-registered, longitudinal experiment, demonstrating the causal relationship between authentic posting and positive affect and mood on a within-person level. Our findings suggest that the extent to which social media use is related to well-being depends on how individuals use it.
Machine learning based early warning system enables accurate mortality risk prediction for COVID-19
Authors: Gao Yue , Cai Guang-Yao , Fang Wei , Li Hua-Yi , Wang Si-Yuan , Chen Lingxi , Yu Yang , Liu Dan , Xu Sen , Cui Peng-Fei , Zeng Shao-Qing , Feng Xin-Xia , Yu Rui-Di , Wang Ya , Yuan Yuan , Jiao Xiao-Fei , Chi Jian-Hua , Liu Jia-Hao , Li Ru-Yuan , Zheng Xu , Song Chun-Yan , Jin Ning , Gong Wen-Jian , Liu Xing-Yu , Huang Lei , Tian Xun , Li Lin , Xing Hui , Ma Ding , Li Chun-Rui , Ye Fei , Gao Qing-Lei
Published: October 2020

Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients’ clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464–0.9778), 0.9760 (0.9613–0.9906), and 0.9246 (0.8763–0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.
Interactions with conspecific outsiders as drivers of cognitive evolution
Authors: Ashton Benjamin J. , Kennedy Patrick , Radford Andrew N.
Published: October 2020

The social intelligence hypothesis (SIH) posits that within-group interactions drive cognitive evolution, but it has received equivocal support. We argue the SIH overlooks a major component of social life: interactions with conspecific outsiders. Competition for vital resources means conspecific outsiders present myriad threats and opportunities in all animal taxa across the social spectrum (from individuals to groups). We detail cognitive challenges generated by conspecific outsiders, arguing these select for ‘Napoleonic’ intelligence; explain potential influences on the SIH; and highlight important considerations when empirically testing these ideas. Including interactions with conspecific outsiders may substantially improve our understanding of cognitive evolution.
Metastable hybridization-based DNA information storage to allow rapid and permanent erasure
Authors: Kim Jangwon , Bae Jin H. , Baym Michael , Zhang David Yu
Published: October 2020

The potential of DNA as an information storage medium is rapidly growing due to advances in DNA synthesis and sequencing. However, the chemical stability of DNA challenges the complete erasure of information encoded in DNA sequences. Here, we encode information in a DNA information solution, a mixture of true message- and false message-encoded oligonucleotides, and enables rapid and permanent erasure of information. True messages are differentiated by their hybridization to a "truth marker” oligonucleotide, and only true messages can be read; binding of the truth marker can be effectively randomized even with a brief exposure to the elevated temperature. We show 8 separate bitmap images can be stably encoded and read after storage at 25 °C for 65 days with an average of over 99% correct information recall, which extrapolates to a half-life of over 15 years at 25 °C. Heating to 95 °C for 5 minutes, however, permanently erases the message.
Predicting cell-to-cell communication networks using NATMI
Authors: Hou Rui , Denisenko Elena , Ong Huan Ting , Ramilowski Jordan A. , Forrest Alistair R. R.
Published: October 2020

Development of high throughput single-cell sequencing technologies has made it cost-effective to profile thousands of cells from diverse samples containing multiple cell types. To study how these different cell types work together, here we develop NATMI (Network Analysis Toolkit for Multicellular Interactions). NATMI uses connectomeDB2020 (a database of 2293 manually curated ligand-receptor pairs with literature support) to predict and visualise cell-to-cell communication networks from single-cell (or bulk) expression data. Using multiple published single-cell datasets we demonstrate how NATMI can be used to identify (i) the cell-type pairs that are communicating the most (or most specifically) within a network, (ii) the most active (or specific) ligand-receptor pairs active within a network, (iii) putative highly-communicating cellular communities and (iv) differences in intercellular communication when profiling given cell types under different conditions. Furthermore, analysis of the Tabula Muris (organism-wide) atlas confirms our previous prediction that autocrine signalling is a major feature of cell-to-cell communication networks, while also revealing that hundreds of ligands and their cognate receptors are co-expressed in individual cells suggesting a substantial potential for self-signalling.
Upregulation of lipid metabolism genes in the breast prior to cancer diagnosis
Authors: Marino Natascia , German Rana , Rao Xi , Simpson Ed , Liu Sheng , Wan Jun , Liu Yunlong , Sandusky George , Jacobsen Max , Stovall Miranda , Cao Sha , Storniolo Anna Maria V.
Published: October 2020

Histologically normal tissue adjacent to the tumor can provide insight of the microenvironmental alterations surrounding the cancerous lesion and affecting the progression of the disease. However, little is known about the molecular changes governing cancer initiation in cancer-free breast tissue. Here, we employed laser microdissection and whole-transcriptome profiling of the breast epithelium prior to and post tumor diagnosis to identify the earliest alterations in breast carcinogenesis. Furthermore, a comprehensive analysis of the three tissue compartments (microdissected epithelium, stroma, and adipose tissue) was performed on the breast donated by either healthy subjects or women prior to the clinical manifestation of cancer (labeled “susceptible normal tissue”). Although both susceptible and healthy breast tissues appeared histologically normal, the susceptible breast epithelium displayed a significant upregulation of genes involved in fatty acid uptake/transport (CD36 and AQP7), lipolysis (LIPE), and lipid peroxidation (AKR1C1). Upregulation of lipid metabolism- and fatty acid transport-related genes was observed also in the microdissected susceptible stromal and adipose tissue compartments, respectively, when compared with the matched healthy controls. Moreover, inter-compartmental co-expression analysis showed increased epithelium-adipose tissue crosstalk in the susceptible breasts as compared with healthy controls. Interestingly, reductions in natural killer (NK)-related gene signature and CD45+/CD20+ cell staining were also observed in the stromal compartment of susceptible breasts. Our study yields new insights into the cancer initiation process in the breast. The data suggest that in the early phase of cancer development, metabolic activation of the breast, together with increased epithelium-adipose tissue crosstalk may create a favorable environment for final cell transformation, proliferation, and survival.
Implementing a context-driven awareness programme addressing household air pollution and tobacco: a FRESH AIR study
Authors: Brakema Evelyn A. , van Gemert Frederik A. , Williams Sian , Sooronbaev Talant , Emilov Berik , Mademilov Maamed , Tabyshova Aizhamal , An Pham Le , Quynh Nguyen Nhat , Hong Le Huynh Thi Cam , Dang Tran Ngoc , van der Kleij Rianne M. J. J. , Chavannes Niels H. , de Jong Corina ,   The FRESH AIR collaborators, Anastasaki Marilena , Akylbekov Azamat , Barton Andy , Bertsias Antonios , Binh Pham Duong Uyen , van Boven Job F. M. , Burges Dennis , Cartwright Lucy , Chatzea Vasiliki E. , Cragg Liza , Dautov Ilyas , Ferarrio Irene , Hedrick Ben , Hopkinson Nick , Isaeva Elvira , Jones Rupert , van Kampen Sanne , Katagira Winceslaus , Kjærgaard Jesper , Kocks Janwillem , Lan Le Thi Tuyet , Linh Tran Thanh Duv , Lionis Christos , Loan Kim Xuan , McEwen Andy , Musinguzi Patrick , Nantanda Rebecca , Ndeezi Grace , Papadakis Sophia , Pinnock Hilary , Pooler Jillian , Poot Charlotte C. , Postma Maarten J. , Poulsen Anja , Powell Pippa , Reventlow Susanne , Sifaki-Pistolla Dimitra , Singh Sally , de Sousa Jaime Correia , Stout James , Østergaard Marianne Stubbe , Tsiligianni Ioanna , Tuan Tran Diep , Tumwine James , Van Le Thanh , Vinh Nguyen Nhu , Walusimbi Simon , Warren Louise
Published: October 2020

Most patients with chronic respiratory disease live in low-resource settings, where evidence is scarcest. In Kyrgyzstan and Vietnam, we studied the implementation of a Ugandan programme empowering communities to take action against biomass and tobacco smoke. Together with local stakeholders, we co-created a train-the-trainer implementation design and integrated the programme into existing local health infrastructures. Feasibility and acceptability, evaluated by the modified Conceptual Framework for Implementation Fidelity, were high: we reached ~15,000 Kyrgyz and ~10,000 Vietnamese citizens within budget (~€11,000/country). The right engaged stakeholders, high compatibility with local contexts and flexibility facilitated programme success. Scores on lung health awareness questionnaires increased significantly to an excellent level among all target groups. Behaviour change was moderately successful in Vietnam and highly successful in Kyrgyzstan. We conclude that contextualising the awareness programme to diverse low-resource settings can be feasible, acceptable and effective, and increase its sustainability. This paper provides guidance to translate lung health interventions to new contexts globally.
VOLCORE, a global database of visible tephra layers sampled by ocean drilling
Authors: Mahony Sue H. , Barnard Nicholas H. , Sparks R. Stephen J. , Rougier Jonathan C.
Published: October 2020

The VOLCORE (Volcanic Core Records) database is a collection of 34,696 visible tephra (volcanic ash and lithological or grain size variations) occurrences reported in the initial reports volumes of all of the Deep Sea Drilling Project (DSDP; 1966–1983), the Ocean Drilling Program (ODP; 1983–2003), the Integrated Ocean Drilling Program (IODP; 2003–2013) and the International Ocean Discovery Program (IODP; 2013-present) up to and including IODP Expedition 381. The combined international ocean drilling programmes (OD) have locations with global coverage. Cored tephra layers and tephra-bearing sediments span timescales from recent to ~150 million years in age. This database is a collection of information about reported visible tephra layers entirely or predominantly composed of volcanic ash. Data include the depth below sea floor, tephra thickness, location, and any reported comments. An approximate age was estimated for most (29,493) of the tephra layers using published age-depth models. The database can be used as a starting point for studies of tephrochronology, volcanology, geochemistry, studies of sediment transport and palaeoclimatology.
Thermophoretic analysis of ligand-specific conformational states of the inhibitory glycine receptor embedded in copolymer nanodiscs
Authors: Bernhard Max , Laube Bodo
Published: October 2020

The glycine receptor (GlyR), a member of the pentameric ligand-gated ion channel family (pLGIC), displays remarkable variations in the affinity and efficacy of the full agonist glycine and the partial agonist taurine depending on the cell system used. Despite detailed insights in the GlyR three-dimensional structure and activation mechanism, little is known about conformational rearrangements induced by these agonists. Here, we characterized the conformational states of the α1 GlyR upon binding of glycine and taurine by microscale thermophoresis expressed in HEK293 cells and Xenopus oocytes after solubilization in amphipathic styrene-maleic acid copolymer nanodiscs. Our results show that glycine and taurine induce different conformational transitions of the GlyR upon ligand binding. In contrast, the variability of agonist affinity is not mediated by an altered conformational change. Thus, our data shed light on specific agonist induced conformational features and mechanisms of pLGIC upon ligand binding determining receptor activation in native environments.
Discovery and validation of candidate genes for grain iron and zinc metabolism in pearl millet [Pennisetum glaucum (L.) R. Br.]
Authors: Mahendrakar Mahesh D. , Parveda Maheshwari , Kishor P. B. Kavi , Srivastava Rakesh K.
Published: October 2020

Pearl millet is an important crop for alleviating micronutrient malnutrition through genomics-assisted breeding for grain Fe (GFeC) and Zn (GZnC) content. In this study, we identified candidate genes related to iron (Fe) and zinc (Zn) metabolism through gene expression analysis and correlated it with known QTL regions for GFeC/GZnC. From a total of 114 Fe and Zn metabolism-related genes that were selected from the related crop species, we studied 29 genes. Different developmental stages exhibited tissue and stage-specific expressions for Fe and Zn metabolism genes in parents contrasting for GFeC and GZnC. Results revealed that PglZIP, PglNRAMP and PglFER gene families were candidates for GFeC and GZnC. Ferritin-like gene, PglFER1 may be the potential candidate gene for GFeC. Promoter analysis revealed Fe and Zn deficiency, hormone, metal-responsive, and salt-regulated elements. Genomic regions underlying GFeC and GZnC were validated by annotating major QTL regions for grain Fe and Zn. Interestingly, PglZIP and PglNRAMP gene families were found common with a previously reported linkage group 7 major QTL region for GFeC and GZnC. The study provides insights into the foundation for functional dissection of different Fe and Zn metabolism genes homologs and their subsequent use in pearl millet molecular breeding programs globally.
Frequency of the TP53 R337H variant in sporadic breast cancer and its impact on genomic instability
Authors: Mathias Carolina , Bortoletto Stéfanne , Centa Ariana , Komechen Heloisa , Lima Rubens S. , Fonseca Aline S. , Sebastião Ana Paula , Urban Cícero A. , Soares Emerson W. S. , Prando Carolina , Figueiredo Bonald C. , Cavalli Iglenir J. , Cavalli Luciane R. , Ribeiro Enilze M. F. S.
Published: October 2020

The R337H is a TP53 germline pathogenic variant that has been associated with several types of cancers, including breast cancer. Our main objective was to determine the frequency of the R337H variant in sporadic breast cancer patients from Paraná state, South Brazil, its association with prognosis and its impact in genomic instability. The genotyping of 805 breast cancer tissues revealed a genotypic and allelic frequency of the R337H variant of 2.36% and 1.18%, respectively. In these R337H+ cases a lower mean age at diagnosis was observed when compared to the R337H-cases. Array-CGH analysis showed that R337H+ patients presented a higher number of copy number alterations (CNAs), compared to the R337H−. These CNAs affected genes and miRNAs that regulate critical cancer signaling pathways; a number of these genes were associated with survival after querying the KMplot database. Furthermore, homozygous (R337H+/R337H+) fibroblasts presented increased levels of copy number variants when compared to heterozygous or R337H− cells. In conclusion, the R337H variant may contribute to 2.36% of the breast cancer cases without family cancer history in Paraná. Among other mechanisms, R337H increases the level of genomic instability, as evidenced by a higher number of CNAs in the R337H+ cases compared to the R337H−.
New chromium(III)-based catalysts for ethylene oligomerization
Authors: Malinowski Jacek , Jacewicz Dagmara , Gawdzik Barbara , Drzeżdżon Joanna
Published: October 2020

The report focuses on the new precatalysts for ethylene oligomerization. The five chromium(III) complex compounds containing the following ligands: dipicolinate anion, oxalate anion, 5-aminopyridine-2-carboxylate anion, 2,2′-bipyridine and 4,4′-dimethoxy-2,2′-bipyridine have been examined towards catalytic activity for ethylene oligomerization. The chromium(III) complexes have been activated by modified methylaluminoxane. The obtained oligomers have been investigated by MALDI-TOF–MS, thermal analysis and infrared spectroscopy. The results revealed that the examined chromium(III) complexes are highly active catalysts for ethylene oligomerization. The values of catalytic activities of the examined complexes are in the range 1860 – 3798 g∙mmol-1∙h-1∙bar-1.
Preliminary insights into the impact of primary radiochemotherapy on the salivary microbiome in head and neck squamous cell carcinoma
Authors: Kumpitsch Christina , Moissl-Eichinger Christine , Pock Jakob , Thurnher Dietmar , Wolf Axel
Published: October 2020

Squamous cell carcinoma is the most common type of throat cancer. Treatment options comprise surgery, radiotherapy, and/or chemo(immuno)therapy. The salivary microbiome is shaped by the disease, and likely by the treatment, resulting in side effects caused by chemoradiation that severely impair patients’ well-being. High-throughput amplicon sequencing of the 16S rRNA gene provides an opportunity to investigate changes in the salivary microbiome in health and disease. In this preliminary study, we investigated alterations in the bacterial, fungal, and archaeal components of the salivary microbiome between healthy subjects and patients with head and neck squamous cell carcinoma before and close to the end point of chemoradiation (“after”). We enrolled 31 patients and 11 healthy controls, with 11 patients providing samples both before and after chemoradiation. Analysis revealed an effect on the bacterial and fungal microbiome, with a partial antagonistic reaction but no effects on the archaeal microbial community. Specifically, we observed an individual increase inCandidasignatures following chemoradiation, whereas the overall diversity of the microbial and fungal signatures decreased significantly after therapy. Thus, our study indicates that the patient microbiome reacts individually to chemoradiation but has potential for future optimization of disease diagnostics and personalized treatments.
Molecular epidemiology of the first wave of severe acute respiratory syndrome coronavirus 2 infection in Thailand in 2020
Authors: Puenpa Jiratchaya , Suwannakarn Kamol , Chansaenroj Jira , Nilyanimit Pornjarim , Yorsaeng Ritthideach , Auphimai Chompoonut , Kitphati Rungrueng , Mungaomklang Anek , Kongklieng Amornmas , Chirathaworn Chintana , Wanlapakorn Nasamon , Poovorawan Yong
Published: October 2020

The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major global concern. Several SARS-CoV-2 gene mutations have been reported. In the current study associations between SARS-CoV-2 gene variation and exposure history during the first wave of the outbreak in Thailand between January and May 2020 were investigated. Forty samples were collected at different time points during the outbreak, and parts of the SARS-CoV-2 genome sequence were used to assess genomic variation patterns. The phylogenetics of the 40 samples were clustered into L, GH, GR, O and T types. T types were predominant in Bangkok during the first local outbreak centered at a boxing stadium and entertainment venues in March 2020. Imported cases were infected with various types, including L, GH, GR and O. In southern Thailand introductions of different genotypes were identified at different times. No clinical parameters were significantly associated with differences in genotype. The results indicated local transmission (type T, Spike protein (A829T)) and imported cases (types L, GH, GR and O) during the first wave in Thailand. Genetic and epidemiological data may contribute to national policy formulation, transmission tracking and the implementation of measures to control viral spread.
Bone-conduction hyperacusis induced by superior canal dehiscence in human: the underlying mechanism
Authors: Guan Xiying , Cheng Y. Song , Galaiya Deepa J. , Rosowski John J. , Lee Daniel J. , Nakajima Hideko Heidi
Published: October 2020

Our ability to hear through bone conduction (BC) has long been recognized, but the underlying mechanism is poorly understood. Why certain perturbations affect BC hearing is also unclear. An example is BC hyperacusis (hypersensitive BC hearing)—an unnerving symptom experienced by patients with superior canal dehiscence (SCD). We measured BC-evoked sound pressures in scala vestibuli (PSV) and scala tympani (PST) at the basal cochlea in cadaveric human ears, and estimated hearing by the cochlear input drive (PDIFF = PSV – PST) before and after creating an SCD. Consistent with clinical audiograms, SCD increased BC-driven PDIFF below 1 kHz. However, SCD affected the individual scalae pressures in unexpected ways: SCD increased PSV below 1 kHz, but had little effect on PST. These new findings are inconsistent with the inner-ear compression mechanism that some have used to explain BC hyperacusis. We developed a computational BC model based on the inner-ear fluid-inertia mechanism, and the simulated effects of SCD were similar to the experimental findings. This experimental-modeling study suggests that (1) inner-ear fluid inertia is an important mechanism for BC hearing, and (2) SCD facilitates the flow of sound volume velocity through the cochlear partition at low frequencies, resulting in BC hyperacusis.
In vivo imaging of long-term accumulation of cancer-derived exosomes using a BRET-based reporter
Authors: Hikita Tomoya , Miyata Mamiko , Watanabe Risayo , Oneyama Chitose
Published: October 2020

Monitoring of exosome dynamics in living organisms is essential to demonstrate the real functions of cancer-derived exosomes. Currently, these have been elucidated in vitro or under non-physiological conditions in vivo in most cases. To overcome these limitations, we developed an imaging method using Antares2-mediated bioluminescence resonance energy transfer (BRET) for observing long-term accumulation of exosomes in vivo. Ectopic expression of CD63-Antares2 effectively labeled exosomes with Antares2, which emitted intense, long-wavelength luminescence suitable for in vivo monitoring. Transplantation of CD63-Antares2-expressing prostate cancer cells into mice allowed determining the amount of cancer-derived exosomes released from primary tumors into the bloodstream and visualizing the long-term homing behavior of exosomes to their target organs or tissues. Interestingly, secreted exosome was decreased upon administration of low dose of dasatinib, an approved tyrosine-kinase inhibitor. The CD63-Antares2 xenograft mouse model will be useful for elucidating the dynamics of cancer-derived exosomes in vivo and evaluating the therapeutic efficacy and mechanism of exosome production inhibitors.