bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulse oximetry screening for detection of congenital heart defects at 1646 m in Albuquerque, New Mexico
Authors: Rao Sruti , Goens M. B. , Myers Orrin B. , Sebesta Emilie A.
Published: September 2020

Aim:

To determine the false-positive rate of pulse oximetry screening at moderate altitude, presumed to be elevated compared with sea level values and assess change in false-positive rate with time.

Methods:

We retrospectively analysed 3548 infants in the newborn nursery in Albuquerque, New Mexico, (elevation 5400 ft) from July 2012 to October 2013. Universal pulse oximetry screening guidelines were employed after 24 hours of life but before discharge. Newborn babies between 36 and 36 6/7 weeks of gestation, weighing >2 kg and babies >37 weeks weighing >1.7 kg were included in the study. Log-binomial regression was used to assess change in the probability of false positives over time.

Results:

Of the 3548 patients analysed, there was one true positive with a posteriorly-malaligned ventricular septal defect and an interrupted aortic arch. Of the 93 false positives, the mean pre- and post-ductal saturations were lower, 92 and 90%, respectively. The false-positive rate before April 2013 was 3.5% and after April 2013, decreased to 1.5%. There was a significant decrease in false-positive rate (p = 0.003, slope coefficient = −0.082, standard error of coefficient = 0.023) with the relative risk of a false positive decreasing at 0.92 (95% CI 0.88–0.97) per month.

Conclusion:

This is the first study in Albuquerque, New Mexico, reporting a high false-positive rate of 1.5% at moderate altitude at the end of the study in comparison to the false-positive rate of 0.035% at sea level. Implementation of the nationally recommended universal pulse oximetry screening was associated with a high false-positive rate in the initial period, thought to be from the combination of both learning curve and altitude. After the initial decline, it remained steadily elevated above sea level, indicating the dominant effect of moderate altitude.
Gender differences in factors associated with body weight misperception
Authors: Kye Su Yeon , Park Keeho
Published: September 2020

Objective:

Gender analysis in health research is important to strengthen our health system. The current study aimed to explore factors related to body weight misperception in a national sample of the general Korean population.

Design:

Cross-sectional study.

Setting:

South Korea, general population.

Participants:

12,900 adults enrolled from the Seventh Korea National Health and Nutrition Examination Survey (2016–2018).

Results:

Disadvantageous socio-economic status was considered a predictor of participants’ misperceptions of themselves as being of a healthy weight despite being overweight and as underweight despite being of a healthy weight, mainly in men. Favourable socio-economic status was considered a predictor of participants’ misperceptions of themselves as being of a healthy weight despite being underweight and as overweight despite being of a healthy weight, mainly in women. Living in an urban area was an independent predictor of men’s misperception of themselves as being of a healthy weight despite being overweight and women’s misperception of themselves as being underweight despite being of a healthy weight. Physical inactivity was a predictor of most misperceptions in women. Psychological variables, such as stress and depression, were not significant predictors of misperception.

Conclusions:

The current study highlighted the gender differences in factors related to body weight misperception. These differences suggested that more sophisticated policies should be formulated to identify solutions to health problems related to body weight.
Have we compromised too much? A critical analysis of nutrition policy in Australia 2007–2018
Authors: I Brandon , Baker Phillip , Lawrence Mark
Published: September 2020

Objective:

A comprehensive nutrition policy containing a broad package of cross-sector and synergistic policy actions is required to attenuate the systemic drivers of poor nutrition. The current study aims to critically analyse trends in the scope of federal nutrition policy actions in Australia between 2007 and 2018 by: (1) describing the changes in nutrition policy actions, benchmarked against an international best-practice policy framework and (2) investigating how and why the scope of these policy actions have changed over time by examining the decision-making processes that led to the establishment of Australia’s Healthy Food Partnership (the Partnership).

Design:

Qualitative case study involving documentary analysis and key-informant interviews. Australian federal government documents (n 10) were analysed against the NOURISHING framework. Key informants (n 6) were interviewed and asked about the Partnership’s decision-making and establishment processes.

Setting:

Australia.

Participants:

Executive Committee (the Partnership’s governing body) and working group members.

Results:

From 2007 to 2018, the scope of Australian national nutrition policy has fluctuated from evidence-informed recommendations for a comprehensive policy to the mostly discrete policy actions of the Partnership. Themes of ‘pragmatism and compromise’, ‘actor relationships and lobbying’ and ‘political context’ were critical drivers for establishing the Partnership.

Conclusion:

The narrowing of Australian nutrition policy reflects a response to political expediency and compromise. This political dynamic highlights a dilemma facing nutrition policy advocates: should (and if so, how) a balance be sought between the aspirational but possibly unrealistic goals, and the limited but likely deliverable outcomes during policy-making processes? These findings have relevance for developing a future comprehensive national nutrition policy.
The desire for death in Portuguese home-care palliative patients: Retrospective analysis of the prevalence and associated factors
Authors: Julião Miguel , Sobral Maria Ana , Calçada Paula , Antunes Bárbara , Runa Daniela , Samorinha Catarina , Chochinov Harvey Max , Breitbart William
Published: September 2020

Objective

Desire for death (DfD) is a complex and multifactorial dimension of end-of-life experience. We aimed to evaluate the prevalence of DfD and its associations, arising within the setting of a tertiary home-based palliative care (PC) unit.

Method

Retrospective analysis of all DfD entries registered in our anonymized database from October 2018 to April 2020.

Results

Of the 163 patients anonymously registered in our database, 122 met entry criteria; 52% were male, the average age was 69 years old; 85% had malignancies, with a mean performance status (PPS) of 56%. The prevalence of DfD was 20%. No statistical differences were observed between patients with and without DfD regarding sex, age, marital status, religion, social support, prior PC or psychological follow-up, type of diagnosis, presence of advanced directives/living will, time since diagnosis and PC team's follow-up time. Statistically significant associations were found between higher PPS scores and DfD (OR = 0.96; 95% confidence interval (CI) [0.93–0.99]); Edmonton Symptom Assessment Scale scores for drowsiness (OR = 4.05; 95% CI [1.42–11.57]), shortness of breath (OR = 3.35; 95% CI [1.09–10.31]), well-being (OR = 7.64; 95% CI [1.63–35.81]). DfD was associated with being depressed (OR = 19.24; 95% CI [3.09–+inf]); feeling anxious (OR = 11.11; 95% CI [2.51–49.29]); HADS anxiety subscale ≥11 (OR = 25.0; 95% CI [2.10–298.29]); will-to-live (OR = 39.53; 95% CI [4.85–321.96]). Patients feeling a burden were more likely to desire death (OR = 14.67; 95% CI [1.85–116.17]), as well as those who were not adapted to the disease (OR = 4.08; 95% CI [1.30–12.84]). In multivariate regression analyses predicting DfD, three independent factors emerged: higher PPS scores were associated with no DfD (aOR = 0.95; 95% CI [0.91–0.99]), while the sense of being a burden (aOR = 12.82; 95% CI [1.31–125.16]) and worse well-being (aOR = 7.72; 95% CI [1.26–47.38]) predicted DfD.

Significance of results

Prevalence of DfD was 20% and consistent with previous Portuguese evidence on DfD in PC inpatients. Both physical and psychosocial factors contribute to a stronger DfD.
Kinematic Rupture Generator Based on 3‐D Spontaneous Rupture Simulations Along Geometrically Rough Faults
Authors: Savran W. H. , Olsen K. B.
Published: September 2020

Spontaneous rupture simulations along geometrically rough faults have been shown to produce realistic far‐field spectra and comparable fits with ground motion metrics such as spectral accelerations and peak motions from Ground Motion Prediction Equations (GMPEs), but they are too computationally demanding for use with physics‐based probabilistic seismic hazard analysis efforts. Here, we present our implementation of a kinematic rupture generator that matches the characteristics of, at least in a statistical sense, rough‐fault spontaneous rupture models. To this end, we analyze ~100 dynamic rupture simulations on strike‐slip faults with Mw ranging from 6.4 to 7.2. We find that our dynamic simulations follow empirical scaling relationships for strike‐slip events and provide source spectra comparable to a source model with ω−2 decay. To define our kinematic source model, we use a regularized Yoffe function parameterized in terms of slip, peak‐time, rise‐time, and rupture initiation time. These parameters are defined through empirical relationships with random fields whose one‐ and two‐point statistics are derived from the dynamic rupture simulations. Our rupture generator reproduces Next Generation Attenuation (NGA) West2 GMPE medians and intraevent standard deviations of spectral accelerations with periods as short as 0.2 s for ensembles of ground motion simulations. Our rupture generator produces kinematic source models for M6.4–7.2 strike‐slip scenarios that can be used in broadband physics‐based probabilistic seismic hazard efforts or to supplement data in areas of limited observations for the development of future GMPEs.
Simulations of Gravitoelastic Correlations for the Sardinian Candidate Site of the Einstein Telescope
Authors: Andric Tomislav , Harms Jan
Published: September 2020

Gravity fluctuations produced by ambient seismic fields are predicted to limit the sensitivity of the next generation, gravitational wave detector Einstein Telescope at frequencies below 20 Hz. The detector will be hosted in an underground infrastructure to reduce seismic disturbances and associated gravity fluctuations. Additional mitigation might be required by monitoring the seismic field and using the data to estimate the associated gravity fluctuations and to subtract the estimate from the detector data, a technique called coherent noise cancelation. In this paper, we present a calculation of correlations between surface displacement of a seismic field and the associated gravitational fluctuations using the spectral element SPECFEM3D Cartesian software. The model takes into account the local topography at a candidate site of the Einstein Telescope at Sardinia. This paper is a first demonstration of SPECFEM3D's capabilities to provide estimates of gravitoelastic correlations, which are required for an optimized deployment of seismometers for gravity noise cancelation.
A Newly Observed Quasi‐stationary Subsurface Anticyclone of the North Brazil Undercurrent at 4°S: The Potiguar Eddy
Authors: Krelling Ana P. M. , da Silveira Ilson C. A. , Polito Paulo S. , Gangopadhyay Avijit , Martins Renato P. , Lima José Antônio M. , Marin Fernando de O.
Published: September 2020

This study describes a newly discovered subsurface anticyclone, called the Potiguar Eddy (PE) centered at about 4°S, 36.5°W, along the western flank of the North Brazil Undercurrent (NBUC). The PE is a quasi‐stationary elliptical feature, with major and minor axes of approximately 330 and 130 km. It extends vertically from 100 to 400 m, with maximum velocities of 0.6 m s−1 and recirculates about 2 Sv of waters from the NBUC. Despite the presence of the PE in subpycnocline waters, the surface flow is predominantly northwestward throughout the year. Analysis of moored current meter data revealed a depth‐dependent variability that reaches its highest values between about 100 and 400 m, coincident with the PE. This variability is found to be associated with a 20‐ to 30‐day second baroclinic mode waves, which can strengthen, weaken, or even reverse the currents of the PE. We highlight the possible causes for this variability to include coastally trapped waves, instabilities, and tropical instability waves or a combination thereof—which opens up new study topics for future research.
A Laboratory Study on the Isotopic Composition of Hg(0) Emitted From Hg‐Enriched Soils in Wanshan Hg Mining Area
Authors: Zhang Hui , Tan Qingyou , Zhang Leiming , Fu Xuewu , Feng Xinbin
Published: September 2020

Soil Hg(0) emissions are an important source of atmospheric mercury (Hg), but the Hg isotopic signatures of this source remain poorly characterized. In this study, the fractionation of Hg isotopes during Hg (0) emissions from Hg‐enriched agricultural and forest soils in Wanshan Hg mining area were investigated through laboratory experiments. Significant mass‐dependent fractionation (MDF) of Hg isotopes and mass independent fractionation of odd Hg isotopes (odd‐MIF) were observed. Mean MDF enrichment factors (ε202HgHg(0)‐soil) of agricultural soil were in the range of −2.03‰ to −1.34‰ for agricultural soil in light‐, light moisture‐, and temperature‐controlled experiments, which were higher than those of forest soil in similar controls (means = −3.38‰ to −1.98‰). Temperature‐controlled experiments exhibited a larger MDF compared to light‐ and light moisture‐controlled experiments. Photoreduction of Hg in agricultural soil in the presence and absence of soil water generated a larger positive odd‐MIF (mean E199HgHg(0)­‐soil = 0.67‰ to 0.76‰, n = 2) than the temperature‐controlled experiments (mean E199HgHg(0)‐­soil = 0.18 ± 0.04‰, 1 SD), whereas the E199HgHg(0)‐­soil of forest soil in temperature controls (mean = 0.23 ± 0.03‰, 1 SD) were higher than that in light (mean = 0.18 ± 0.06‰, 1 SD) and light moisture‐controlled experiments (mean = −0.03 ± 0.06‰, 1 SD). It is speculated that photoreducible Hg (II) likely dominantly bound to S‐containing ligands in agricultural soil but to both S‐containing and sulfurless ligands in forest soil, resulting in significant positive odd‐MIF in Hg(0) product during photoreduction in the former case and a small magnitude of positive to some negative odd‐MIF in the latter case.
Simulating Observations of Southern Ocean Clouds and Implications for Climate
Authors: Gettelman A. , Bardeen C. G. , McCluskey C. S. , Järvinen E. , Stith J. , Bretherton C. , McFarquhar G. , Twohy C. , D'Alessandro J. , Wu W.
Published: September 2020

Southern Ocean (S. Ocean) clouds are important for climate prediction. Yet previous global climate models failed to accurately represent cloud phase distributions in this observation‐sparse region. In this study, data from the Southern Ocean Clouds, Radiation, Aerosol, Transport Experimental Study (SOCRATES) experiment is compared to constrained simulations from a global climate model (the Community Atmosphere Model, CAM). Nudged versions of CAM are found to reproduce many of the features of detailed in situ observations, such as cloud location, cloud phase, and boundary layer structure. The simulation in CAM6 has improved its representation of S. Ocean clouds with adjustments to the ice nucleation and cloud microphysics schemes that permit more supercooled liquid. Comparisons between modeled and observed hydrometeor size distributions suggest that the modeled hydrometeor size distributions represent the dual peaked shape and form of observed distributions, which is remarkable given the scale difference between model and observations. Comparison to satellite observations of cloud physics is difficult due to model assumptions that do not match retrieval assumptions. Some biases in the model's representation of S. Ocean clouds and aerosols remain, but the detailed cloud physical parameterization provides a basis for process level improvement and direct comparisons to observations. This is crucial because cloud feedbacks and climate sensitivity are sensitive to the representation of S. Ocean clouds.
Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation
Authors: Wang Chao , Chen Zhen , Nie Litong , Tang Mengfan , Feng Xu , Su Dan , Zhang Huimin , Xiong Yun , Park Jeong-Min , Chen Junjie
Published: September 2020

The ERK1/2 pathway is one of the most commonly dysregulated pathways in human cancers and controls many vital cellular processes. Although many ERK1/2 kinase substrates have been identified, the diversity of ERK1/2 mediated processes suggests the existence of additional targets. Here, we identified Deoxyhypusine synthase (DHPS), an essential hypusination enzyme regulating protein translation, as a major and direct-binding protein of ERK1/2. Further experiments showed that ERK1/2 phosphorylate DHPS at Ser-233 site. The Ser-233 phosphorylation of DHPS by ERK1/2 is important for its function in cell proliferation. Moreover, we found that higher DHPS expression correlated with poor prognosis in lung adenocarcinoma and increased resistance to inhibitors of the ERK1/2 pathway. In summary, our results suggest that ERK1/2-mediated DHPS phosphorylation is an important mechanism that underlies protein translation and that DHPS expression is a potent biomarker of response to therapies targeting ERK1/2-pathway.
Glucocorticoids induce differentiation and chemoresistance in ovarian cancer by promoting ROR1-mediated stemness
Authors: Karvonen Hanna , Arjama Mariliina , Kaleva Laura , Niininen Wilhelmiina , Barker Harlan , Koivisto-Korander Riitta , Tapper Johanna , Pakarinen Päivi , Lassus Heini , Loukovaara Mikko , Bützow Ralf , Kallioniemi Olli , Murumägi Astrid , Ungureanu Daniela
Published: September 2020

Glucocorticoids are routinely used in the clinic as anti-inflammatory and immunosuppressive agents as well as adjuvants during cancer treatment to mitigate the undesirable side effects of chemotherapy. However, recent studies have indicated that glucocorticoids may negatively impact the efficacy of chemotherapy by promoting tumor cell survival, heterogeneity, and metastasis. Here, we show that dexamethasone induces upregulation of ROR1 expression in ovarian cancer (OC), including platinum-resistant OC. Increased ROR1 expression resulted in elevated RhoA, YAP/TAZ, and BMI-1 levels in a panel of OC cell lines as well as primary ovarian cancer patient-derived cells, underlining the translational relevance of our studies. Importantly, dexamethasone induced differentiation of OC patient-derived cells ex vivo according to their molecular subtype and the phenotypic expression of cell differentiation markers. High-throughput drug testing with 528 emerging and clinical oncology compounds of OC cell lines and patient-derived cells revealed that dexamethasone treatment increased the sensitivity to several AKT/PI3K targeted kinase inhibitors, while significantly decreasing the efficacy of chemotherapeutics such as taxanes, as well as anti-apoptotic compounds such as SMAC mimetics. On the other hand, targeting ROR1 expression increased the efficacy of taxane drugs and SMAC mimetics, suggesting new combinatorial targeted treatments for patients with OC.
Gut microbiota patterns associated with somatostatin in patients undergoing pancreaticoduodenectomy: a prospective study
Authors: Li Guan-Qun , Zhang Tao , Yang Wei-Guang , Zhong Hao-Liang , Xiao Peng , Liu Li-Wei , Wang Yong-Wei , Chen Hua , Kong Rui , Wang Gang , Tan Hong-Tao , Bai Xue-Wei , Li Yi-Long , Li Le , Sun Bei
Published: September 2020

Postoperative pancreatic fistula (POPF) is a common and dreaded complication after pancreaticoduodenectomy (PD). The gut microbiota has been considered as an crucial mediator of postoperative complications, however, the precise roles of gut microbiota in POPF are unclear. A prospective study was developed to explore the effects of somatostatin on gut microbiota and we aim to identify the microbial alterations in the process of POPF. A total of 45 patients were randomly divided into PD group or additional somatostatin therapy group. The fecal sample of each patient was collected preoperatively and postoperatively and the gut microbiota was analyzed by 16S rRNA sequencing. Our study found that somatostatin therapy was independent risk factor for the occurrence of POPF, and it reduced the microbial diversity and richness in patients. At genus level, somatostatin therapy led to a decreased abundance in Bifidobacterium, Subdoligranulum and Dubosiella, whereas the abundance of Akkermansia, Enterococcus and Enterobacter were increased. The abundance levels of certain bacteria in the gut microbiota have significantly shifted in patients with POPF. The LEfSe analysis revealed that Ruminococcaceae could be used as microbial markers for distinguishing patients with high risk of POPF. Furthermore, Verrucomicrobia and Akkermansia could be used as preoperative biomarkers for identifying patients without POPF. Our prospective study highlights the specific communities related with somatostatin therapy and discovers POPF-associated microbial marker, which suggests that gut microbiota may become a diagnostic biomarker and potential therapeutic target for POPF.
STAT5 promotes accessibility and is required for BATF-mediated plasticity at the Il9 locus
Authors: Fu Yongyao , Wang Jocelyn , Panangipalli Gayathri , Ulrich Benjamin J. , Koh Byunghee , Xu Chengxian , Kharwadkar Rakshin , Chu Xiaona , Wang Yue , Gao Hongyu , Wu Wenting , Sun Jie , Tepper Robert S. , Zhou Baohua , Janga Sarath Chandra , Yang Kai , Kaplan Mark H.
Published: September 2020

T helper cell differentiation requires lineage-defining transcription factors and factors that have shared expression among multiple subsets. BATF is required for development of multiple Th subsets but functions in a lineage-specific manner. BATF is required for IL-9 production in Th9 cells but in contrast to its function as a pioneer factor in Th17 cells, BATF is neither sufficient nor required for accessibility at the Il9 locus. Here we show that STAT5 is the earliest factor binding and remodeling the Il9 locus to allow BATF binding in both mouse and human Th9 cultures. The ability of STAT5 to mediate accessibility for BATF is observed in other Th lineages and allows acquisition of the IL-9-secreting phenotype. STAT5 and BATF convert Th17 cells into cells that mediate IL-9-dependent effects in allergic airway inflammation and anti-tumor immunity. Thus, BATF requires the STAT5 signal to mediate plasticity at the Il9 locus.
Calreticulin del52 and ins5 knock-in mice recapitulate different myeloproliferative phenotypes observed in patients with MPN
Authors: Benlabiod Camélia , Cacemiro Maira da Costa , Nédélec Audrey , Edmond Valérie , Muller Delphine , Rameau Philippe , Touchard Laure , Gonin Patrick , Constantinescu Stefan N. , Raslova Hana , Villeval Jean-Luc , Vainchenker William , Plo Isabelle , Marty Caroline
Published: September 2020

Somatic mutations in the calreticulin (CALR) gene are associated with approximately 30% of essential thrombocythemia (ET) and primary myelofibrosis (PMF). CALR mutations, including the two most frequent 52 bp deletion (del52) and 5 bp insertion (ins5), induce a frameshift to the same alternative reading frame generating new C-terminal tails. In patients, del52 and ins5 induce two phenotypically distinct myeloproliferative neoplasms (MPNs). They are equally found in ET, but del52 is more frequent in PMF. We generated heterozygous and homozygous conditional inducible knock-in (KI) mice expressing a chimeric murine CALR del52 or ins5 with the human mutated C-terminal tail to investigate their pathogenic effects on hematopoiesis. Del52 induces greater phenotypic changes than ins5 including thrombocytosis, leukocytosis, splenomegaly, bone marrow hypocellularity, megakaryocytic lineage amplification, expansion and competitive advantage of the hematopoietic stem cell compartment. Homozygosity amplifies these features, suggesting a distinct contribution of homozygous clones to human MPNs. Moreover, homozygous del52 KI mice display features of a penetrant myelofibrosis-like disorder with extramedullary hematopoiesis linked to splenomegaly, megakaryocyte hyperplasia and the presence of reticulin fibers. Overall, modeling del52 and ins5 mutations in mice successfully recapitulates the differences in phenotypes observed in patients.
Interleukin-8 as a candidate for thymoma identification and recurrence surveillance
Authors: Gao Shilin , Jiang Jiahao , Jin Chun , Gao Jian , Xiong Dian , Yang Pengjie , Cui Shuzhong , Yang Wenhao , Leng Qibin , Dong Jihong , Chen Gang , Liu Junzhen , Wang Li , Ke Aiwu , Wang Haikun , Ding Jianyong
Published: September 2020

Thymoma is the most common tumor of the anterior mediastinum. Routine imaging methods such as computed tomography or magnetic resonance imaging often lead to misdiagnosis between thymoma and other thymic abnormalities. Therefore, urgently needed is to develop a new diagnostic strategy. Here we identify interleukin-8 (IL-8) as a biomarker for auxiliary diagnosis of thymoma. We find that IL-8 levels in naïve T cells are markedly elevated in patients with thymoma compared to those with other thymic tumors. IL-8 levels in naive T cells are significantly decreased after surgical resection in thymoma patients, and rise again when thymoma recurs. A receiver operating characteristic curve analysis shows that IL-8 evaluation performs well in thymoma identification, with high specificities and sensitivities. We also observe significant clinical relevance between IL-8 levels in naïve T cells and clinicopathological features. In conclusion, our study suggests that IL-8 is a biomarker for thymoma identification and recurrence surveillance.
Integrated molecular characterization reveals potential therapeutic strategies for pulmonary sarcomatoid carcinoma
Authors: Yang Zhenlin , Xu Jiachen , Li Lin , Li Renda , Wang Yalong , Tian Yanhua , Guo Wei , Wang Zhijie , Tan Fengwei , Ying Jianming , Jiao Yuchen , Gao Shugeng , Wang Jie , Gao Yibo , He Jie
Published: September 2020

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung cancer with poor prognosis. Here, we perform multi-omics analysis of 56 PSC samples, 14 of which are microdissected to analyze intratumoral heterogeneity. We report the mutational landscape of PSC. The epithelial and sarcomatoid components share numerous genomic alterations, indicating a common progenitor. We find that epithelial-mesenchymal transition (EMT) plays important roles in the carcinogenesis of PSC. The pan-cancer analysis reveals high tumor mutation burden and leukocyte fraction of PSC. Integrated molecular classification shows three subgroups with distinct biology, prognosis and potential therapeutic strategies. Actionable mutations are enriched in C1 and C2, patients in C3 have a significantly longer overall survival, and C1 and C2 exhibit T-cell inflamed microenvironments. The three subgroups show molecular similarities to specific subtypes of conventional lung cancer. In conclusion, our study reveals the molecular characteristics and provides entry points for the treatment of PSC.
SV-HotSpot: detection and visualization of hotspots targeted by structural variants associated with gene expression
Authors: Eteleeb Abdallah M. , Quigley David A. , Zhao Shuang G. , Pham Duy , Yang Rendong , Dehm Scott M. , Luo Jingqin , Feng Felix Y. , Dang Ha X. , Maher Christopher A.
Published: September 2020

Whole genome sequencing (WGS) has enabled the discovery of genomic structural variants (SVs), including those targeting intergenic and intronic non-coding regions that eluded previous exome focused strategies. However, the field currently lacks an automated tool that analyzes SV candidates to identify recurrent SVs and their targeted sites (hotspot regions), visualizes these genomic events within the context of various functional elements, and evaluates their potential effect on gene expression. To address this, we developed SV-HotSpot, an automated tool that integrates SV candidates, copy number alterations, gene expression, and genome annotations (e.g. gene and regulatory elements) to discover, annotate, and visualize recurrent SVs and their targeted hotspot regions that may affect gene expression. We applied SV-HotSpot to WGS and matched transcriptome data from metastatic castration resistant prostate cancer patients and rediscovered recurrent SVs targeting coding and non-coding functional elements known to promote prostate cancer progression and metastasis. SV-HotSpot provides a valuable resource to integrate SVs, gene expression, and genome annotations for discovering biologically relevant SVs altering coding and non-coding genome. SV-HotSpot is available athttps://github.com/ChrisMaherLab/SV-HotSpot.
Immune activation correlates with and predicts CXCR4 co-receptor tropism switch in HIV-1 infection
Authors: Connell Bridgette J. , Hermans Lucas E. , Wensing Annemarie M. J. , Schellens Ingrid , Schipper Pauline J. , van Ham Petra M. , de Jong Dorien T. C. M. , Otto Sigrid , Mathe Tholakele , Moraba Robert , Borghans José A. M. , Papathanasopoulos Maria A. , Kruize Zita , Venter Francois W. D. , Kootstra Neeltje A. , Tempelman Hugo , Tesselaar Kiki , Nijhuis Monique
Published: September 2020

HIV-1 cell entry is mediated by binding to the CD4-receptor and chemokine co-receptors CCR5 (R5) or CXCR4 (X4). R5-tropic viruses are predominantly detected during early infection. A switch to X4-tropism often occurs during the course of infection. X4-tropism switching is strongly associated with accelerated disease progression and jeopardizes CCR5-based HIV-1 cure strategies. It is unclear whether host immunological factors play a causative role in tropism switching. We investigated the relationship between immunological factors and X4-tropism in a cross-sectional study in HIV-1 subtype C (HIV-1C)-infected patients and in a longitudinal HIV-1 subtype B (HIV-1B) seroconverter cohort. Principal component analysis identified a cluster of immunological markers (%HLA-DR+ CD4+ T-cells, %CD38+HLA-DR+ CD4+ T-cells, %CD38+HLA-DR+ CD8+ T-cells, %CD70+ CD4+ T-cells, %CD169+ monocytes, and absolute CD4+ T-cell count) in HIV-1C patients that was independently associated with X4-tropism (aOR 1.044, 95% CI 1.003–1.087, p = 0.0392). Analysis of individual cluster contributors revealed strong correlations of two markers of T-cell activation (%HLA-DR+ CD4+ T-cells, %HLA-DR+CD38+ CD4+ T-cells) with X4-tropism, both in HIV-1C patients (p = 0.01;p = 0.03) and HIV-1B patients (p = 0.0003;p = 0.0001). Follow-up data from HIV-1B patients subsequently revealed that T-cell activation precedes and independently predicts X4-tropism switching (aHR 1.186, 95% CI 1.065–1.321, p = 0.002), providing novel insights into HIV-1 pathogenesis and CCR5-based curative strategies.
Retraction Note: Novel green synthesis and antioxidant, cytotoxicity, antimicrobial, antidiabetic, anticholinergics, and wound healing properties of cobalt nanoparticles containing Ziziphora clinopodioides Lam leaves extract
Authors: Hou Huifang , Mahdavi Behnam , Paydarfard Sogand , Mahdi Zangeneh Mohammad , Zangeneh Akram , Sadeghian Nastaran , Taslimi Parham , Erduran Vildan , Sen Fatih
Published: September 2020

Editor's Note: this Article has been retracted; the Retraction Note is available at https://www.nature.com/articles/s41598-020-71843-9
FADS genetic and metabolomic analyses identify the ∆5 desaturase (FADS1) step as a critical control point in the formation of biologically important lipids
Authors: Reynolds Lindsay M. , Dutta Rahul , Seeds Michael C. , Lake Kirsten N. , Hallmark Brian , Mathias Rasika A. , Howard Timothy D. , Chilton Floyd H.
Published: September 2020

Humans have undergone intense evolutionary selection to optimize their capacity to generate necessary quantities of long chain (LC-) polyunsaturated fatty acid (PUFA)-containing lipids. To better understand the impact of genetic variation within a locus of three FADS genes (FADS1, FADS2, and FADS3) on a diverse family of lipids, we examined the associations of 247 lipid metabolites (including four major classes of LC-PUFA-containing molecules and signaling molecules) with common and low-frequency genetic variants located within the FADS locus. Genetic variation in the FADS locus was strongly associated (p < 1.2 × 10–8) with 52 LC-PUFA-containing lipids and signaling molecules, including free fatty acids, phospholipids, lyso-phospholipids, and an endocannabinoid. Notably, the majority (80%) of FADS-associated lipids were not significantly associated with genetic variants outside of this FADS locus. These findings highlight the central role genetic variation at the FADS locus plays in regulating levels of physiologically critical LC-PUFA-containing lipids that participate in innate immunity, energy homeostasis, and brain development/function.
Interplay of social distancing and border restrictions for pandemics via the epidemic renormalisation group framework
Authors: Cacciapaglia Giacomo , Sannino Francesco
Published: September 2020

One of the biggest threats to humanity are pandemics. In our global society they can rage around the world with an immense toll in terms of human, economic and social impact. Forecasting the spreading of a pandemic is, therefore, paramount in helping governments to enforce a number of social and economic measures, apt at curbing the pandemic and dealing with its aftermath. We demonstrate that the epidemic renormalisation group approach to pandemics provides an effective and simple way to investigate the dynamics of disease transmission and spreading across different regions of the world. The framework also allows for reliable projections on the impact of travel limitations and social distancing measures on global epidemic spread. We test and calibrate it on reported COVID-19 cases while unveiling the mechanism that governs the delay in the relative peaks of newly infected cases among different regions of the globe. We discover that social distancing measures are more effective than travel limitations across borders in delaying the epidemic peak. We further provide the link to compartmental models such as the time-honoured SIR-like models. We also show how to generalise the framework to account for the interactions across several regions of the world, replacing or complementing large scale simulations.
Two coupled chains are simpler than one: field-induced chirality in a frustrated spin ladder
Authors: Pikulski Marek , Shiroka Toni , Casola Francesco , Reyes Arneil P. , Kuhns Philip L. , Wang Shuang , Ott Hans-Rudolf , Mesot Joël
Published: September 2020

Although the frustrated (zigzag) spin chain is the Drosophila of frustrated magnetism, our understanding of a pair of coupled zigzag chains (frustrated spin ladder) in a magnetic field is still lacking. We address this problem through nuclear magnetic resonance (NMR) experiments on BiCu$$_2$$

2

PO$$_6$$

6

in magnetic fields up to 45 T, revealing a field-induced spiral magnetic structure. Conjointly, we present advanced numerical calculations showing that even a moderate rung coupling dramatically simplifies the phase diagram below half-saturation magnetization by stabilizing a field-induced chiral phase. Surprisingly for a one-dimensional model, this phase and its response to Dzyaloshinskii-Moriya (DM) interactions adhere to classical expectations. While explaining the behavior at the highest accessible magnetic fields, our results imply a different origin for the solitonic phases occurring at lower fields in BiCu$$_2$$

2

PO$$_6$$

6

. An exciting possibility is that the known, DM-mediated coupling between chirality and crystal lattice may give rise to a new kind of spin-Peierls instability.
Revealing soil legacy phosphorus to promote sustainable agriculture in Brazil
Authors: Pavinato Paulo S. , Cherubin Maurício R. , Soltangheisi Amin , Rocha Gustavo C. , Chadwick Dave R. , Jones Davey L.
Published: September 2020

Exploiting native soil phosphorus (P) and the large reservoirs of residual P accumulated over decades of cultivation, namely “legacy P”, has great potential to overcome the high demand of P fertilisers in Brazilian cropping systems. Long-term field experiments have shown that a large proportion (> 70%) of the surplus P added via fertilisers remains in the soil, mainly in forms not readily available to crops. An important issue is if the amount of legacy P mobilized from soil is sufficient for the crop nutritional demand and over how long this stored soil P can be effectively ‘mined’ by crops in a profitable way. Here we mapped the spatial–temporal distribution of legacy P over the past 50 years, and discussed possible agricultural practices that could increase soil legacy P usage by plants in Brazil. Mineral fertiliser and manure applications have resulted in ~ 33.4 Tg of legacy P accumulated in the agricultural soils from 1967 to 2016, with a current annual surplus rate of 1.6 Tg. Following this same rate, soil legacy P may reach up to 106.5 Tg by 2050. Agricultural management practices to enhance soil legacy P usage by crops includes increasing soil pH by liming, crop rotation, double-cropping, inter-season cover crops, no-tillage system and use of modern fertilisers, in addition to more efficient crop varieties and inoculation with P solubilising microorganisms. The adoption of these practices could increase the use efficiency of P, substantially reducing the new input of fertilisers and thus save up to 31.8 Tg of P fertiliser use (US$ 20.8 billion) in the coming decades. Therefore, exploring soil legacy P is imperative to reduce the demand for mineral fertilisers while promoting long-term P sustainability in Brazil.
Distinct chemotactic behavior in the original Escherichia coli K-12 depending on forward-and-backward swimming, not on run-tumble movements
Authors: Kinosita Yoshiaki , Ishida Tsubasa , Yoshida Myu , Ito Rie , Morimoto Yusuke V. , Goto Kazuki , Berry Richard M. , Nishizaka Takayuki , Sowa Yoshiyuki
Published: September 2020

Most motile bacteria are propelled by rigid, helical, flagellar filaments and display distinct swimming patterns to explore their favorable environments. Escherichia coli cells have a reversible rotary motor at the base of each filament. They exhibit a run-tumble swimming pattern, driven by switching of the rotational direction, which causes polymorphic flagellar transformation. Here we report a novel swimming mode in E. coli ATCC10798, which is one of the original K-12 clones. High-speed tracking of single ATCC10798 cells showed forward and backward swimming with an average turning angle of 150°. The flagellar helicity remained right-handed with a 1.3 μm pitch and 0.14 μm helix radius, which is consistent with the feature of a curly type, regardless of motor switching; the flagella of ATCC10798 did not show polymorphic transformation. The torque and rotational switching of the motor was almost identical to the E. coli W3110 strain, which is a derivative of K-12 and a wild-type for chemotaxis. The single point mutation of N87K in FliC, one of the filament subunits, is critical to the change in flagellar morphology and swimming pattern, and lack of flagellar polymorphism. E. coli cells expressing FliC(N87K) sensed ascending a chemotactic gradient in liquid but did not spread on a semi-solid surface. Based on these results, we concluded that a flagellar polymorphism is essential for spreading in structured environments.
Identifying volatile organic compounds used for olfactory navigation by homing pigeons
Authors: Zannoni Nora , Wikelski Martin , Gagliardo Anna , Raza Atif , Kramer Stefan , Seghetti Chiara , Wang Nijing , Edtbauer Achim , Williams Jonathan
Published: September 2020

Many bird species have the ability to navigate home after being brought to a remote, even unfamiliar location. Environmental odours have been demonstrated to be critical to homeward navigation in over 40 years of experiments, yet the chemical identity of the odours has remained unknown. In this study, we investigate potential chemical navigational cues by measuring volatile organic compounds (VOCs): at the birds’ home-loft; in selected regional forest environments; and from an aircraft at 180 m. The measurements showed clear regional, horizontal and vertical spatial gradients that can form the basis of an olfactory map for marine emissions (dimethyl sulphide, DMS), biogenic compounds (terpenoids) and anthropogenic mixed air (aromatic compounds), and temporal changes consistent with a sea-breeze system. Air masses trajectories are used to examine GPS tracks from released birds, suggesting that local DMS concentrations alter their flight directions in predictable ways. This dataset reveals multiple regional-scale real-world chemical gradients that can form the basis of an olfactory map suitable for homing pigeons.
Structural and functional modelling of SARS-CoV-2 entry in animal models
Authors: Brooke Greg N. , Prischi Filippo
Published: September 2020

SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 26th July 2020, has infected over 16 million people. Despite the urgent need to find effective therapeutics, research on SARS-CoV-2 has been affected by a lack of suitable animal models. To facilitate the development of medical approaches and novel treatments, we compared the ACE2 receptor, and TMPRSS2 and Furin proteases usage of the SARS-CoV-2 Spike glycoprotein in human and in a panel of animal models, i.e. guinea pig, dog, cat, rat, rabbit, ferret, mouse, hamster and macaque. Here we showed that ACE2, but not TMPRSS2 or Furin, has a higher level of sequence variability in the Spike protein interaction surface, which greatly influences Spike protein binding mode. Using molecular docking simulations we compared the SARS-CoV and SARS-CoV-2 Spike proteins in complex with the ACE2 receptor and showed that the SARS-CoV-2 Spike glycoprotein is compatible to bind the human ACE2 with high specificity. In contrast, TMPRSS2 and Furin are sufficiently similar in the considered hosts not to drive susceptibility differences. Computational analysis of binding modes and protein contacts indicates that macaque, ferrets and hamster are the most suitable models for the study of inhibitory antibodies and small molecules targeting the SARS-CoV-2 Spike protein interaction with ACE2. Since TMPRSS2 and Furin are similar across species, our data also suggest that transgenic animal models expressing human ACE2, such as the hACE2 transgenic mouse, are also likely to be useful models for studies investigating viral entry.
NMR resonance assignment and dynamics of profilin from Heimdallarchaeota
Authors: Haq Syed Razaul , Survery Sabeen , Hurtig Fredrik , Lindås Ann-Christin , Chi Celestine N.
Published: September 2020

The origin of the eukaryotic cell is an unsettled scientific question. The Asgard superphylum has emerged as a compelling target for studying eukaryogenesis due to the previously unseen diversity of eukaryotic signature proteins. However, our knowledge about these proteins is still relegated to metagenomic data and very little is known about their structural properties. Additionally, it is still unclear if these proteins are functionally homologous to their eukaryotic counterparts. Here, we expressed, purified and structurally characterized profilin from Heimdallarchaeota in the Asgard superphylum. The structural analysis shows that while this profilin possesses similar secondary structural elements as eukaryotic profilin, it contains additional secondary structural elements that could be critical for its function and an indication of divergent evolution.
Modeling root system growth around obstacles
Authors: Jin Wencheng , Aufrecht Jayde , Patino-Ramirez Fernando , Cabral Heidy , Arson Chloé , Retterer Scott T.
Published: September 2020

State-of-the-Art models of Root System Architecture (RSA) do not allow simulating root growth around rigid obstacles. Yet, the presence of obstacles can be highly disruptive to the root system. We grew wheat seedlings in sealed petri dishes without obstacle and in custom 3D-printed rhizoboxes containing obstacles. Time-lapse photography was used to reconstruct the wheat root morphology network. We used the reconstructed wheat root network without obstacle to calibrate an RSA model implemented in the R-SWMS software. The root network with obstacles allowed calibrating the parameters of a new function that models the influence of rigid obstacles on wheat root growth. Experimental results show that the presence of a rigid obstacle does not affect the growth rate of the wheat root axes, but that it does influence the root trajectory after the main axis has passed the obstacle. The growth recovery time, i.e. the time for the main root axis to recover its geotropism-driven growth, is proportional to the time during which the main axis grows along the obstacle. Qualitative and quantitative comparisons between experimental and numerical results show that the proposed model successfully simulates wheat RSA growth around obstacles. Our results suggest that wheat roots follow patterns that could inspire the design of adaptive engineering flow networks.
Functional validation of DvABCB1 as a receptor of Cry3 toxins in western corn rootworm, Diabrotica virgifera virgifera
Authors: Niu Xiping , Kassa Adane , Hasler James , Griffin Samantha , Perez-Ortega Claudia , Procyk Lisa , Zhang Jun , Kapka-Kitzman Deirdre M. , Nelson Mark E. , Lu Albert
Published: September 2020

Western corn rootworm (WCR), Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae), is a serious insect pest in the major corn growing areas of North America and in parts of Europe. WCR populations with resistance to Bacillus thuringiensis (Bt) toxins utilized in commercial transgenic traits have been reported, raising concerns over their continued efficacy in WCR management. Understanding the modes of action of Bt toxins is important for WCR control and resistance management. Although different classes of proteins have been identified as Bt receptors for lepidopteran insects, identification of receptors in WCR has been limited with no reports of functional validation. Our results demonstrate that heterologous expression of DvABCB1 in Sf9 and HEK293 cells conferred sensitivity to the cytotoxic effects of Cry3A toxins. The result was further validated using knockdown of DvABCB1 by RNAi which rendered WCR larvae insensitive to a Cry3A toxin. However, silencing of DvABCB2 which is highly homologous to DvABCB1 at the amino acid level, did not reduce the sensitivity of WCR larvae to a Cry3A toxin. Furthermore, our functional studies corroborate different mode-of-actions for other insecticidal proteins including Cry34Ab1/35Ab1, Cry6Aa1, and IPD072Aa against WCR. Finally, reduced expression and alternatively spliced transcripts of DvABCB1 were identified in a mCry3A-resistant strain of WCR. Our results provide the first clear demonstration of a functional receptor in the molecular mechanism of Cry3A toxicity in WCR and confirmed its role in the mechanism of resistance in a mCry3A resistant strain of WCR.