bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Government Responses to Unemployment Reduce the Impact of Unemployment on Suicide?
Authors: Shand Fiona , Duffy Luke , Torok Michelle
Published: January 2021

Abstract. Background: Unemployment is a well-documented risk factor for suicide. Findings from a number of studies suggest that government policy plays a crucial role in mediating the unemployment–suicide relationship. Aims: Our review was designed to assess whether government policies aimed at managing unemployment can moderate the impact of unemployment on suicide and self-harm. Method: A systematic search of the Medline, ProQuest, Scopus, and Web of Science databases was conducted. All original, English-language, peer-reviewed studies examining the impact of unemployment policy on rates of suicide or self-harm were eligible for inclusion. Results: Six unique studies were identified, each using an ecological design and suicide deaths as the outcome. Three of five studies looking at unemployment benefits found a negative association with suicide rates. Studies examining the impact of active unemployment policy and employment protection legislation found evidence of beneficial effects. The effects of the policies were small and had particular benefit in reducing suicide rates among men. Limitations: The ecological designs used may limit conclusions around causality. It is unclear whether the findings generalize to those in lower- and middle-income countries. Conclusion: The findings suggest that unemployment policies can mitigate the relationship between unemployment and suicide, particularly among men.
An Exploration of Barriers to Suicide Prevention Messaging With US Veterans
Authors: Karras Elizabeth , Levandowski Brooke A. , McCarten Janet M.
Published: January 2021

Abstract. Background: Communication campaigns offer a portable intervention to effectively reach and engage target populations at risk for suicide including US veterans. Few studies have evaluated such efforts, and still fewer have examined factors that contribute to failed suicide prevention messaging. Aims: We aimed to examine characteristics of suicide prevention messages and persuasive processes that may underlie failed communicative intervention with US veterans. Method: Telephone interviews were completed with veterans ( N = 33) from June to September 2016 using a semi-structured interview guide. Interview transcripts were coded by the authors with NVivo using a constant comparison analytic strategy. Results: Several reasons emerged for why suicide prevention messaging may fail to produce intended responses among veterans. Participants identified message features (e.g., language, images, messenger) and communication strategies that may diminish campaign effects. Limitations: Findings are not generalizable, are limited to participants who used VA healthcare and were not suicidal, and are subject to several biases. Conclusion: This work provides initial insights into barriers to effective message use with veterans.
A Computationally Efficient Hybrid Framework for Polarimetric Calibration of Quad‐Pol SAR Data
Authors: Maiti Abhisek , Kumar Shashi , Tolpekin Valentyn , Agarwal Shefali
Published: January 2021

Polarimetric Synthetic Aperture Radar (PolSAR) calibration is an essential preprocessing step that must be performed to ensure that the data quality is adequate. This, in turn, helps to minimize the propagation of errors in any further data processing or information extraction. Crosstalk and channel imbalance are two major distortions found to be present in the uncalibrated polarimetric SAR data. The PolSAR calibration mainly aims to reduce these two distortions revealing the true scattering pattern of the targets. In this regard, Quegan's algorithm and Ainsworth algorithm are two widely used algorithms for the PolSAR calibration. In this study, the accuracy and efficiency of these two algorithms have been thoroughly compared using suitable metrics. It has been shown that the Ainsworth algorithm performs better than Quegan's in terms of accuracy at the cost of poor computational efficiency. The data quality metrics also highlight the better calibration accuracy of the Ainsworth algorithm. The issue of higher computational complexity has been effectively addressed by coupling both of these algorithms. Evidently, the computational cost has been reduced in the case of the proposed algorithm. The polarization orientation angle (POA) shift is another distortion caused by the topographic variations present in the target scene. Therefore, correction of POA shift has been incorporated in this research by coupling it with the PolSAR calibration. Subsequently, the improvement in the scattering has been observed. In essence, the proposed algorithm coupled with the correction of POA shift rectifies the major polarimetric distortions with adequate accuracy and computational efficiency.
Deformation Behavior and Inferred Seismic Properties of Tonalitic Migmatites at the Time of Pre‐melting, Partial Melting, and Post‐Solidification
Authors: Shao Yilun , Piazolo Sandra , Liu Yongjiang , Lee Amicia L. , Jin Wei , Li Weimin , Liang Chenyue , Wen Quanbo
Published: January 2021

As seismic data from the lower crust becomes more readily available, it is important to link seismic properties to the ongoing processes within lower crustal evolution. This includes high temperature, pre‐ and post‐migmatization solid state deformation as well as melt‐present deformation. We selected two tonalitic migmatites with variable former melt content (one metatexite and one diatexite) from the lower crustal Daqingshan area, northern North China Craton to assess the link between seismic properties and rock structure and rheology. Field observation along with microstructural features suggest that the characteristics of hornblende and plagioclase within the residuum of the metatexite can be used to derive information on the pre‐melt deformation. Residuum's plagioclase CPO (crystallographic preferred orientations) is consistent with high temperature dislocation creep as the main deformation mechanism; similarly, hornblende shows a strong CPO related to dislocation creep. During syn‐melt (melt present) conditions, phenocrysts of plagioclase in the metatexite's neosome and K‐feldspar and peritectic hornblende in the diatexite's neosome are present. The rheology of the rock was dominated by melt; hence is inferred to follow Newtonian flow. After melt crystallization deformation is minor but again dominated by dislocation creep. The seismic properties (seismic velocity, anisotropy, Vp/Vs ratio, etc.) for pre‐ and post‐melt have similar values expected values for solid mafic rocks, whilst the syn‐melt seismic velocities are generally lower and Vp/Vs ratios and seismic anisotropies are higher.
Measurements of Iceberg Melt Rates Using High‐Resolution GPS and Iceberg Surface Scans
Authors: Schild Kristin M. , Sutherland David A. , Elosegui Pedro , Duncan Daniel
Published: January 2021

Increasing freshwater input to the subpolar North Atlantic through iceberg melting can influence fjord‐scale to basin‐scale ocean circulation. However, the magnitude, timing, and distribution of this freshwater have been challenging to quantify due to minimal direct observations of subsurface iceberg geometry and melt rates. Here we present novel in situ methods capturing iceberg change at high‐temporal and ‐spatial resolution using four high‐precision GPS units deployed on two large icebergs (>500 m length). In combination with measurements of surface and subsurface geometry, we calculate iceberg melt rates between 0.10 and 0.27 m/d over the 9‐day survey. These melt rates are lower than those proposed in previous studies, likely due to using individual subsurface iceberg geometries in calculations. In combining these new measurements of iceberg geometry and melt rate with the broad spatial coverage of remote sensing, we can better predict the impact of increasing freshwater injection from the Greenland Ice Sheet.
Energy Conversion Within Current Sheets in the Earth's Quasi‐Parallel Magnetosheath
Authors: Schwartz Steven J. , Kucharek Harald , Farrugia Charles J. , Trattner Karlheinz , Gingell Imogen , Ergun Robert E. , Strangeway Robert , Gershman Daniel
Published: January 2021

Shock waves in collisionless plasmas rely on kinetic processes to convert the primary incident bulk flow energy into thermal energy. That conversion is initiated within a thin transition layer but may continue well into the downstream region. At the Earth's bow shock, the region downstream of shock locations where the interplanetary magnetic field is nearly parallel to the shock normal is highly turbulent. We study the distribution of thin current events in this magnetosheath. Quantification of the energy dissipation rate made by the Magnetospheric Multiscale spacecraft shows that these isolated intense currents are distributed uniformly throughout the magnetosheath and convert a significant fraction (5%–11%) of the energy flux incident at the bow shock.
Marine Vertical Gravity Gradients Reveal the Global Distribution and Tectonic Significance of “Seesaw” Ridge Propagation
Authors: Harper Hugh , Tozer Brook , Sandwell David T. , Hey Richard N.
Published: January 2021

The segmentation of mid‐ocean ridges is a defining characteristic of seafloor spreading, yet some tectonic processes operating at segment boundaries remain poorly understood. Here, we analyze new satellite‐derived vertical gravity gradient (VGG) data, which reveal an abundance of off‐axis seafloor features that are oblique to ridges and transform faults and thus reflect the occurrence of ridge propagation at some segment boundaries. However, unlike many propagating ridges, these features commonly reverse direction leaving W‐shaped signatures in the seafloor which we refer to as “seesaw propagators” (SSPs). Using the VGG, we have documented these globally and find that: (1) SSPs are ubiquitous on seafloor that formed at half spreading rates between 10 and 40 mm year−1 and their total length is about 1/3 that of fracture zones. (2) The lithospheric age offset across SSPs (0–2.5 Ma) is less than transform faults (2–10 Ma), which likely reflects a rheological threshold, whereby only young and weak lithosphere allows for “non‐rigid” SSP behavior. (3) Isostatic modeling of well‐surveyed SSPs confirms that they formed on young and thin (3 km) lithosphere. (4) The directional changes of SSPs in both time and space appear largely uncorrelated and cannot be explained by previous regional‐scale models invoked to explain unidirectional ridge propagation and thus require a different driving force.
Observed Water Exchange Between the South China Sea and Java Sea Through Karimata Strait
Authors: Xu T. F. , Wei Z. X. , Susanto R. D. , Li S. J. , Wang Y. G. , Wang Y. , Xu X. Q. , Agustiadi T. , Trenggono M. , Sulistyo B. , Setiawan A. , Kuswardani A. , Fang G. H.
Published: January 2021

Volume, heat and freshwater transports from the South China Sea (SCS) to the Java Sea through the Karimata Strait are estimated based on direct measurements of current, temperature, salinity, and satellite observations. Subject to strong seasonal variability, the volume, heat, freshwater transports are −1.98 ± 0.23 Sv (1 Sv = 106 m3/s), −209.68 ± 15.19 TW (1 TW = 1012 W), −99.87 ± 15.11 mSv (1 mSv = 10‐3 Sv) in boreal winter, and 0.47 ± 0.20 Sv, 61.06 ± 15.46 TW, 31.67 ± 8.76 mSv in boreal summer, respectively (negative transport defined from SCS to Java Sea). The annual mean volume, heat and freshwater transports are −0.78 ± 0.12 Sv, −77.31 ± 4.99 TW, and −30.87 ± 6.15 mSv, respectively. The freshwater transport through Karimata Strait is as large as 42% of rainfall input to the entire Indonesian seas in boreal winter, thereby modulating the Indonesian Throughflow (ITF) through the “freshwater plug” effect in the Makassar Strait. The interannual variability of the transports is not significantly correlated to the Indian Ocean Dipole and El Niño‐Southern Oscillation. There is a significant decreasing trend of volume and heat transports from the SCS to Java Sea over the period of 1997–2015, with a reduction of 0.26 Sv and 15 TW, respectively. The freshwater transport decreases 12.29 mSv by 2016 compared with that in 2009, equivalent to 33.2%–49.72% of the annual mean freshwater transport during 2009–2016. This decreasing trend would play contradictory roles in the decadal trend of ITF transport by building a “freshwater plug” in the southern Makassar Strait and a ‘buoyant plume’ in the Indo‐Australian Basin, respectively.
Constraints on Hydraulic Anisotropy From Periodic Pumping Tests Using a Double‐Packer System
Authors: Cheng Y. , Renner J.
Published: January 2021

Periodic pumping tests are now being used to characterize subsurface hydraulic parameters owing to several advantages over conventional tests, for example, option of superposing periodic excitations on transients by the data processing in the frequency domain. We derive an analytical model of periodic pumping tests using a double‐packer system to isolate an injection interval in a borehole penetrating either a confined or unconfined anisotropic aquifer. The model, which is apt for injectivity analysis and axial interference analysis, was evaluated by comparing it to previously presented solutions of the hydraulic diffusion equation considering appropriate limits regarding interval length, storage capacity of the interval, and the aquifer specific yield. The axial interference analysis constrains the ratio of axial‐to‐radial hydraulic conductivity. Radial conductivity and specific storage are constrained by the injectivity analysis prescribing conductivity anisotropy ratios. The combination of the two analyses narrows down the range of estimated hydraulic properties. The application of our model to field data from a fault zone in crystalline rocks yields a subvertical conductivity at least 10 times greater than the horizontal value, which agrees qualitatively with the fault geometry. By proper choice of the pumping period, axial interference analysis can be used to not only assess the integrity of packers and their immediate surrounding but also to extend our understanding of subsurface features.
Innovative Pediatric Resident Training in Behavioral Health and Communication: Pilot Study Results
Authors: Herbst Rachel Becker , Burkhardt Mary Carol , Filigno Stephanie S. , Kerr Amy , Boat Thomas F.
Published: January 2021

Objective: Pediatricians and pediatric residency program directors recognize that training on social-emotional and behavioral health in residency is not adequate preparation for future practice. Pediatric psychologists’ expertise in the behavioral dimensions of health and facilitating learners’ skill development can help meet these training gaps. We developed a novel resident training curriculum in pediatric primary care focused on knowledge and skill development in the key areas of behavioral health and effective communication. This study examined the curriculum’s feasibility, acceptability, and impact on residents’ skill development in addressing social-emotional and behavioral health concerns. Methods: Using a mixed-methods, quasi-experimental design, we explored the curriculum’s effectiveness by comparing subjective and objective measures completed by residents from the intervention clinic ( n = 32) and matched control clinic residents ( n = 32). Ten intervention clinic residents provided qualitative data about the curriculum’s impact. Results: Results indicated that the curriculum was feasible and acceptable. Intervention group residents reported greater knowledge and skills associated with behavioral health screening and surveillance than control group participants and demonstrated significant improvement in the communication skills. Conclusions: Our results highlight the role of pediatric psychologists as coleaders and collaborators within pediatric medical training programs to design and implement training curricula to improve the care and attention that behavioral health issues receive in the primary care setting.

Implications for Impact Statement

Pediatricians and residency program directors recognize that behavioral health and communication training in residency is insufficient. This mixed-methods, quasi-experimental study demonstrates how an innovative curriculum closes gaps, promotes skill development, and provides a foundation for future curricular development and evaluation.
Nanoparticle T-cell engagers as a modular platform for cancer immunotherapy
Authors: Alhallak Kinan , Sun Jennifer , Wasden Katherine , Guenthner Nicole , O’Neal Julie , Muz Barbara , King Justin , Kohnen Daniel , Vij Ravi , Achilefu Samuel , DiPersio John F. , Azab Abdel Kareem
Published: January 2021

T-cell-based immunotherapy, such as CAR-T cells and bispecific T-cell engagers (BiTEs), has shown promising clinical outcomes in many cancers; however, these therapies have significant limitations, such as poor pharmacokinetics and the ability to target only one antigen on the cancer cells. In multiclonal diseases, these therapies confer the development of antigen-less clones, causing tumor escape and relapse. In this study, we developed nanoparticle-based bispecific T-cell engagers (nanoBiTEs), which are liposomes decorated with anti-CD3 monoclonal antibodies (mAbs) targeting T cells, and mAbs targeting the cancer antigen. We also developed a nanoparticle that targets multiple cancer antigens by conjugating multiple mAbs against multiple cancer antigens for T-cell engagement (nanoMuTEs). NanoBiTEs and nanoMuTEs have a long half-life of about 60 h, which enables once-a-week administration instead of continuous infusion, while maintaining efficacy in vitro and in vivo. NanoMuTEs targeting multiple cancer antigens showed greater efficacy in myeloma cells in vitro and in vivo, compared to nanoBiTEs targeting only one cancer antigen. Unlike nanoBiTEs, treatment with nanoMuTEs did not cause downregulation (or loss) of a single antigen, and prevented the development of antigen-less tumor escape. Our nanoparticle-based immuno-engaging technology provides a solution for the major limitations of current immunotherapy technologies.
A vacuum ultraviolet laser with a submicrometer spot for spatially resolved photoemission spectroscopy
Authors: Mao Yuanhao , Zhao Dong , Yan Shen , Zhang Hongjia , Li Juan , Han Kai , Xu Xiaojun , Guo Chuan , Yang Lexian , Zhang Chaofan , Huang Kun , Chen Yulin
Published: January 2021

Vacuum ultraviolet (VUV) lasers have demonstrated great potential as the light source for various spectroscopies, which, if they can be focused into a small beam spot, will not only allow investigation of mesoscopic materials and structures but also find application in the manufacture of nano-objects with excellent precision. In this work, we report the construction of a 177 nm VUV laser that can achieve a record-small (~0.76 μm) focal spot at a long focal length (~45 mm) by using a flat lens without spherical aberration. The size of the beam spot of this VUV laser was tested using a metal grating and exfoliated graphene flakes, and we demonstrated its application in a fluorescence spectroscopy study on pure and Tm3+-doped NaYF4 microcrystals, revealing a new emission band that cannot be observed in the traditional up-conversion process. In addition, this laser system would be an ideal light source for spatially and angle-resolved photoemission spectroscopy.
Functional connectivity during frustration: a preliminary study of predictive modeling of irritability in youth
Authors: Scheinost Dustin , Dadashkarimi Javid , Finn Emily S. , Wambach Caroline G. , MacGillivray Caroline , Roule Alexandra L. , Niendam Tara A. , Pine Daniel S. , Brotman Melissa A. , Leibenluft Ellen , Tseng Wan-Ling
Published: January 2021

Irritability cuts across many pediatric disorders and is a common presenting complaint in child psychiatry; however, its neural mechanisms remain unclear. One core pathophysiological deficit of irritability is aberrant responses to frustrative nonreward. Here, we conducted a preliminary fMRI study to examine the ability of functional connectivity during frustrative nonreward to predict irritability in a transdiagnostic sample. This study included 69 youths (mean age = 14.55 years) with varying levels of irritability across diagnostic groups: disruptive mood dysregulation disorder (n = 20), attention-deficit/hyperactivity disorder (n = 14), anxiety disorder (n = 12), and controls (n = 23). During fMRI, participants completed a frustrating cognitive flexibility task. Frustration was evoked by manipulating task difficulty such that, on trials requiring cognitive flexibility, “frustration” blocks had a 50% error rate and some rigged feedback, while “nonfrustration” blocks had a 10% error rate. Frustration and nonfrustration blocks were randomly interspersed. Child and parent reports of the affective reactivity index were used as dimensional measures of irritability. Connectome-based predictive modeling, a machine learning approach, with tenfold cross-validation was conducted to identify networks predicting irritability. Connectivity during frustration (but not nonfrustration) blocks predicted child-reported irritability (ρ = 0.24, root mean square error = 2.02, p = 0.03, permutation testing, 1000 iterations, one-tailed). Results were adjusted for age, sex, medications, motion, ADHD, and anxiety symptoms. The predictive networks of irritability were primarily within motor-sensory networks; among motor-sensory, subcortical, and salience networks; and between these networks and frontoparietal and medial frontal networks. This study provides preliminary evidence that individual differences in irritability may be associated with functional connectivity during frustration, a phenotype-relevant state.
The role of host promiscuity in the invasion process of a seaweed holobiont
Authors: Bonthond Guido , Bayer Till , Krueger-Hadfield Stacy A , Stärck Nadja , Wang Gaoge , Nakaoka Masahiro , Künzel Sven , Weinberger Florian
Published: January 2021

Invasive species are co-introduced with microbiota from their native range and also interact with microbiota found in the novel environment to which they are introduced. Host flexibility toward microbiota, or host promiscuity, is an important trait underlying terrestrial plant invasions. To test whether host promiscuity may be important in macroalgal invasions, we experimentally simulated an invasion in a common garden setting, using the widespread invasive macroalga Agarophyton vermiculophyllum as a model invasive seaweed holobiont. After disturbing the microbiota of individuals from native and non-native populations with antibiotics, we monitored the microbial succession trajectories in the presence of a new source of microbes. Microbial communities were strongly impacted by the treatment and changed compositionally and in terms of diversity but recovered functionally by the end of the experiment in most respects. Beta-diversity in disturbed holobionts strongly decreased, indicating that different populations configure more similar –or more common– microbial communities when exposed to the same conditions. This decline in beta-diversity occurred not only more rapidly, but was also more pronounced in non-native populations, while individuals from native populations retained communities more similar to those observed in the field. This study demonstrates that microbial communities of non-native A. vermiculophyllum are more flexibly adjusted to the environment and suggests that an intraspecific increase in host promiscuity has promoted the invasion process of A. vermiculophyllum. This phenomenon may be important among invasive macroalgal holobionts in general.
Integrative analysis of genome-wide association studies identifies novel loci associated with neuropsychiatric disorders
Authors: Yao Xueming , Glessner Joseph T. , Li Junyi , Qi Xiaohui , Hou Xiaoyuan , Zhu Chonggui , Li Xiaoge , March Michael E. , Yang Liu , Mentch Frank D. , Hain Heather S. , Meng Xinyi , Xia Qianghua , Hakonarson Hakon , Li Jin
Published: January 2021

Neuropsychiatric disorders, such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), bipolar disorder (BIP), and major depressive disorder (MDD) share common clinical presentations, suggesting etiologic overlap. A substantial proportion of SNP-based heritability for neuropsychiatric disorders is attributable to genetic components, and genome-wide association studies (GWASs) focusing on individual diseases have identified multiple genetic loci shared between these diseases. Here, we aimed at identifying novel genetic loci associated with individual neuropsychiatric diseases and genetic loci shared by neuropsychiatric diseases. We performed multi-trait joint analyses and meta-analysis across five neuropsychiatric disorders based on their summary statistics from the Psychiatric Genomics Consortium (PGC), and further carried out a replication study of ADHD among 2726 cases and 16299 controls in an independent pediatric cohort. In the multi-trait joint analyses, we found five novel genome-wide significant loci for ADHD, one novel locus for BIP, and ten novel loci for MDD. We further achieved modest replication in our independent pediatric dataset. We conducted fine-mapping and functional annotation through an integrative multi-omics approach and identified causal variants and potential target genes at each novel locus. Gene expression profile and gene-set enrichment analysis further suggested early developmental stage expression pattern and postsynaptic membrane compartment enrichment of candidate genes at the genome-wide significant loci of these neuropsychiatric disorders. Therefore, through a multi-omics approach, we identified novel genetic loci associated with the five neuropsychiatric disorders which may help to better understand the underlying molecular mechanism of neuropsychiatric diseases.
Long-term risk of subsequent cancer incidence among hereditary and nonhereditary retinoblastoma survivors
Authors: Schonfeld Sara J. , Kleinerman Ruth A. , Abramson David H. , Seddon Johanna M. , Tucker Margaret A. , Morton Lindsay M.
Published: January 2021

Background

Increased sarcoma and melanoma risks after hereditary retinoblastoma are well established, whereas less is known about epithelial subsequent malignant neoplasms (SMNs) and risks for multiple (≥2) SMNs.

Methods

Leveraging long-term follow-up and detailed histologic information, we quantified incident SMN risk among 1128 hereditary and 924 nonhereditary retinoblastoma survivors (diagnosed 1914–2006; follow-up through 2016). Standardised incidence ratios (SIRs) compared cancer risk after retinoblastoma relative to the general population. We estimated cumulative incidence accounting for competing risk of death.

Results

Hereditary survivors had statistically significantly increased SMN risk (N = 239; SIR = 11.9; 95% confidence interval [CI] 10.4–13.5), with SIRs >80-fold for sarcomas, nasal cavity tumours and pineoblastoma. Significantly increased risks were also observed for melanoma and central nervous system, oral cavity and breast SMNs (SIRs = 3.1–17), but not the uterus, kidney, lung, bladder, pancreas or other types. Cumulative incidence 50 years following hereditary retinoblastoma was 33.1% (95% CI 29.0–37.2) for a first SMN and 6.0% (95% CI 3.8–8.2) for a second SMN. SMN risk was not increased after nonhereditary retinoblastoma (N = 25; SIR = 0.8; 95% CI 0.5–1.2).

Conclusion

Beyond the established sarcoma and melanoma risks after hereditary retinoblastoma, we demonstrate increased risk for a more limited number of epithelial malignancies than previously suggested. Cumulative incidence estimates emphasise long-term SMN burden after hereditary retinoblastoma.
Comparative analysis of drug response and gene profiling of HER2-targeted tyrosine kinase inhibitors
Authors: Conlon Neil T. , Kooijman Jeffrey J. , van Gerwen Suzanne J. C. , Mulder Winfried R. , Zaman Guido J. R. , Diala Irmina , Eli Lisa D. , Lalani Alshad S. , Crown John , Collins Denis M.
Published: January 2021

Background

Human epidermal growth factor 2 (HER2/ERBB2) is frequently amplified/mutated in cancer. The tyrosine kinase inhibitors (TKIs) lapatinib, neratinib, and tucatinib are FDA-approved for the treatment of HER2-positive breast cancer. Direct comparisons of the preclinical efficacy of the TKIs have been limited to small-scale studies. Novel biomarkers are required to define beneficial patient populations.

Methods

In this study, the anti-proliferative effects of the three TKIs were directly compared using a 115 cancer cell line panel. Novel TKI response/resistance markers were identified through cross-analysis of drug response profiles with mutation, gene copy number and expression data.

Results

All three TKIs were effective against HER2-amplified breast cancer models; neratinib showing the most potent activity, followed by tucatinib then lapatinib. Neratinib displayed the greatest activity inHER2-mutant andEGFR-mutant cells. High expression ofHER2,VTCN1,CDK12, andRAC1correlated with response to all three TKIs. DNA damage repair genes were associated with TKI resistance.BRCA2mutations were correlated with neratinib and tucatinib response, and high expression ofATM,BRCA2, andBRCA1were associated with neratinib resistance.

Conclusions

Neratinib was the most effective HER2-targeted TKI againstHER2-amplified, -mutant, andEGFR-mutant cell lines. This analysis revealed novel resistance mechanisms that may be exploited using combinatorial strategies.
MicroRNA-194: a novel regulator of glucagon-like peptide-1 synthesis in intestinal L cells
Authors: Wang Jiao , Zhao Di , Ding Cheng-Zhi , Guo Feng , Wu Li-Na , Huang Feng-Jiao , Liu Yan-Ling , Zhao Shui-Ying , Xin Ying , Ma Sheng-Nan , Ji Hong-Fei , Wang Xiang , Wei Li-Rui
Published: January 2021

In the status of obesity, the glucagon-like peptide-1 (GLP-1) level usually declines and results in metabolic syndrome. This study aimed to investigate the intracellular mechanism of GLP-1 synthesis in L cells from the perspective of microRNA (miRNA). In the present study, we found that GLP-1 level was down-regulated in the plasma and ileum tissues of obese mice, while the ileac miR-194 expression was up-regulated. In vitro experiments indicated that miR-194 overexpression down-regulated GLP-1 level, mRNA levels of proglucagon gene (gcg) and prohormone convertase 1/3 gene (pcsk1), and the nuclear protein level of beta-catenin (β-catenin). Further investigation confirmed that β-catenin could promote gcg transcription through binding to transcription factor 7-like 2 (TCF7L2). miR-194 suppressed gcg mRNA level via negatively regulating TCF7L2 expression. What’s more, forkhead box a1 (Foxa1) could bind to the promoter of pcsk1 and enhanced its transcription. miR-194 suppressed pcsk1 transcription through targeting Foxa1. Besides, the interference of miR-194 reduced palmitate (PA)-induced cell apoptosis and the anti-apoptosis effect of miR-194 inhibitor was abolished by TCF7L2 knockdown. Finally, in HFD-induced obese mice, the silence of miR-194 significantly elevated GLP-1 level and improved the metabolic symptoms caused by GLP-1 deficiency. To sum up, our study found that miR-194 suppressed GLP-1 synthesis in L cells via inhibiting TCF7L2-mediated gcg transcription and Foxa1-mediated pcsk1 transcription. Meanwhile, miR-194 took part in the PA-induced apoptosis of L cells.
Survival of salivary gland cancer stem cells requires mTOR signaling
Authors: Andrade Nathalia P. , Warner Kristy A. , Zhang Zhaocheng , Pearson Alexander T. , Mantesso Andrea , Guimaraēs Douglas M. , Altemani Albina , Mariano Fernanda V. , Nunes Fabio D. , Nör Jacques E.
Published: January 2021

Advanced salivary gland mucoepidermoid carcinoma (MEC) is a relentless cancer that exhibits resistance to conventional chemotherapy. As such, treatment for patients with advanced MEC is tipically radical surgery and radiotherapy. Facial disfigurement and poor quality of life are frequent treatment challenges, and many patients succumb to loco-regional recurrence and/or metastasis. We know that cancer stem-like cells (CSC) drive MEC tumorigenesis. The current study tests the hypothesis that MEC CSC are sensitive to therapeutic inhibition of mTOR. Here, we report a correlation between the long-term clinical outcomes of 17 MEC patients and the intratumoral expression of p-mTOR (p = 0.00294) and p-S6K1 (p = 0.00357). In vitro, we observed that MEC CSC exhibit constitutive activation of the mTOR signaling pathway (i.e., mTOR, AKT, and S6K1), unveiling a potential strategy for targeted ablation of these cells. Using a panel of inhibitors of the mTOR pathway, i.e., rapamycin and temsirolimus (mTOR inhibitors), buparlisib and LY294002 (AKT inhibitors), and PF4708671 (S6K1 inhibitor), we observed consistently dose-dependent decrease in the fraction of CSC, as well as inhibition of secondary sphere formation and self-renewal in three human MEC cell lines (UM-HMC-1,-3A,-3B). Notably, therapeutic inhibition of mTOR with rapamycin or temsirolimus induced preferential apoptosis of CSC, when compared to bulk tumor cells. In contrast, conventional chemotherapeutic drugs (cisplatin, paclitaxel) induced preferential apoptosis of bulk tumor cells and accumulation of CSC. In vivo, therapeutic inhibition of mTOR with temsirolimus caused ablation of CSC and downregulation of Bmi-1 expression (major inducer of stem cell self-renewal) in MEC xenografts. Transplantation of MEC cells genetically silenced for mTOR into immunodeficient mice corroborated the results obtained with temsirolimus. Collectively, these data demonstrated that mTOR signaling is required for CSC survival, and unveiled the therapeutic potential of targeting the mTOR pathway for elimination of highly tumorigenic cancer stem-like cells in salivary gland mucoepidermoid carcinoma.
Gaussian-preserved, non-volatile shape morphing in three-dimensional microstructures for dual-functional electronic devices
Authors: Tian Ziao , Xu Borui , Wan Guangchao , Han Xiaomin , Di Zengfeng , Chen Zi , Mei Yongfeng
Published: January 2021

Motile plant structures such as Mimosa pudica leaves, Impatiens glandulifera seedpods, and Dionaea muscipula leaves exhibit fast nastic movements in a few seconds or less. This motion is stimuli-independent mechanical movement following theorema egregium rules. Artificial analogs of tropistic motion in plants are exemplified by shape-morphing systems, which are characterized by high functional robustness and resilience for creating 3D structures. However, all shape-morphing systems developed so far rely exclusively on continuous external stimuli and result in slow response. Here, we report a Gaussian-preserved shape-morphing system to realize ultrafast shape morphing and non-volatile reconfiguration. Relying on the Gaussian-preserved rules, the transformation can be triggered by mechanical or thermal stimuli within a microsecond. Moreover, as localized energy minima are encountered during shape morphing, non-volatile configuration is preserved by geometrically enhanced rigidity. Using this system, we demonstrate a suite of electronic devices that are reconfigurable, and therefore, expand functional diversification.
The impact of COVID-19 and social distancing on people with Parkinson’s disease: a survey study
Authors: Feeney Megan P. , Xu Yaqian , Surface Matthew , Shah Hiral , Vanegas-Arroyave Nora , Chan Amanda K. , Delaney Elizabeth , Przedborski Serge , Beck James C. , Alcalay Roy N.
Published: January 2021

As the COVID-19 pandemic continues to affect the international community, very little is known about its impact on the health and day-to-day activities of people with Parkinson’s disease (PwPD). To better understand the emotional and behavioral consequences of the public health policies implemented to mitigate the spread of SARS-CoV-2 in PwPD, and to explore the factors contributing to accessing alternative health care mechanisms, such as telehealth, we administered an anonymous knowledge, attitude, and practice survey to PwPD and care partners, via the mailing lists of the Parkinson’s Foundation and Columbia University Parkinson’s Disease Center of Excellence with an average response rate of 19.3%. Sufficient information was provided by 1,342 PwPD to be included in the final analysis. Approximately half of respondents reported a negative change in PD symptoms, with 45–66% reporting mood disturbances. Telehealth use increased from 9.7% prior to the pandemic to 63.5% during the pandemic. Higher income and higher education were associated with telehealth use. Services were more often used for doctor’s appointment than physical, occupational, speech, or mental health therapies. Almost half (46%) of PwPD preferred to continue using telehealth always or sometimes after the coronavirus outbreak had ended. Having received support/instruction for telehealth and having a care partner, friend, or family member to help them with the telehealth visit increased the likelihood of continuous use of telehealth after the pandemic ended. Taken together, PD symptoms and management practices were markedly affected by COVID-19. Given the observed demographic limitations of telehealth, expanding its implementation to include additional physical, occupational, psychological, and speech therapies, increasing support for telehealth, as well as reaching underserved (low income) populations is urgently required.
The human O-GlcNAcome database and meta-analysis
Authors: Wulff-Fuentes Eugenia , Berendt Rex R. , Massman Logan , Danner Laura , Malard Florian , Vora Jeet , Kahsay Robel , Olivier-Van Stichelen Stephanie
Published: January 2021

Over the past 35 years, ~1700 articles have characterized protein O-GlcNAcylation. Found in almost all living organisms, this post-translational modification of serine and threonine residues is highly conserved and key to biological processes. With half of the primary research articles using human models, the O-GlcNAcome recently reached a milestone of 5000 human proteins identified. Herein, we provide an extensive inventory of human O-GlcNAcylated proteins, their O-GlcNAc sites, identification methods, and corresponding references (www.oglcnac.mcw.edu). In the absence of a comprehensive online resource for O-GlcNAcylated proteins, this list serves as the only database of O-GlcNAcylated proteins. Based on the thorough analysis of the amino acid sequence surrounding 7002 O-GlcNAc sites, we progress toward a more robust semi-consensus sequence for O-GlcNAcylation. Moreover, we offer a comprehensive meta-analysis of human O-GlcNAcylated proteins for protein domains, cellular and tissue distribution, and pathways in health and diseases, reinforcing that O-GlcNAcylation is a master regulator of cell signaling, equal to the widely studied phosphorylation.
AC–DC electropenetrography unmasks fine temporal details of feeding behaviors for two tick species on unsedated hosts
Authors: Reif Kathryn E. , Backus Elaine A.
Published: January 2021

Ticks are significant nuisance pests and vectors of pathogens for humans, companion animals, and livestock. Limited information on tick feeding behaviors hampers development and rigorous evaluation of tick and tick-borne pathogen control measures. To address this obstacle, the present study examined the utility of AC–DC electropenetrography (EPG) to monitor feeding behaviors of adult Dermacentor variabilis and Amblyomma americanum in real-time. EPG recording was performed during early stages of slow-phase tick feeding using an awake calf host. Both tick species exhibited discernable and stereotypical waveforms of low-, medium-, and high-frequencies. Similar waveform families and types were observed for both tick species; however, species-specific waveform structural differences were also observed. Tick waveforms were hierarchically categorized into three families containing seven types. Some waveform types were conserved by both species (e.g., Types 1b, 1c, 2b, 2c) while others were variably performed among species and individually recorded ticks (e.g., Types 1a, 2a, 2d). This study provides a proof-of-principle demonstration of the feasibility for using EPG to monitor, evaluate, and compare tick feeding behaviors, providing a foundation for future studies aimed at correlating specific feeding behaviors with waveforms, and ultimately the influence of control measures and pathogens on tick feeding behaviors.
Author Correction: Improvement of nerve imaging speed with coherent anti-Stokes Raman scattering rigid endoscope using deep-learning noise reduction
Authors: Yamato Naoki , Niioka Hirohiko , Miyake Jun , Hashimoto Mamoru
Published: January 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Why do inequality and deprivation produce high crime and low trust?
Authors: De Courson Benoît , Nettle Daniel
Published: January 2021

Humans sometimes cooperate to mutual advantage, and sometimes exploit one another. In industrialised societies, the prevalence of exploitation, in the form of crime, is related to the distribution of economic resources: more unequal societies tend to have higher crime, as well as lower social trust. We created a model of cooperation and exploitation to explore why this should be. Distinctively, our model features a desperation threshold, a level of resources below which it is extremely damaging to fall. Agents do not belong to fixed types, but condition their behaviour on their current resource level and the behaviour in the population around them. We show that the optimal action for individuals who are close to the desperation threshold is to exploit others. This remains true even in the presence of severe and probable punishment for exploitation, since successful exploitation is the quickest route out of desperation, whereas being punished does not make already desperate states much worse. Simulated populations with a sufficiently unequal distribution of resources rapidly evolve an equilibrium of low trust and zero cooperation: desperate individuals try to exploit, and non-desperate individuals avoid interaction altogether. Making the distribution of resources more equal or increasing social mobility is generally effective in producing a high cooperation, high trust equilibrium; increasing punishment severity is not.
Asthma-prone areas modeling using a machine learning model
Authors: Razavi-Termeh Seyed Vahid , Sadeghi-Niaraki Abolghasem , Choi Soo-Mi
Published: January 2021

Nowadays, owing to population growth, increasing environmental pollution, and lifestyle changes, the number of asthmatics has significantly increased. Therefore, the purpose of our study was to determine the asthma-prone areas in Tehran, Iran considering environmental, spatial factors. Initially, we built a spatial database using 872 locations of children with asthma and 13 environmental factors affecting the disease—distance to parks and streets, rainfall, temperature, humidity, pressure, wind speed, particulate matter (PM 10 and PM 2.5), ozone (O3), sulfur dioxide (SO2), carbon monoxide (CO), and nitrogen dioxide (NO2). Subsequently, utilizing this spatial database, a random forest (RF) machine learning model, and a geographic information system, we prepared a map of asthma-prone areas. For modeling and validation, we deployed 70% and 30%, respectively, of the locations of children with asthma. The results of spatial autocorrelation and RF model showed that the criteria of distance to parks and streets as well as PM 2.5 and PM 10 had the greatest impact on asthma occurrence in the study area. Spatial autocorrelation analyses indicated that the distribution of asthma cases was not random. According to receiver operating characteristic results, the RF model had good accuracy (the area under the curve was 0.987 and 0.921, respectively, for training and testing data).
Ranking of a wide multidomain set of predictor variables of children obesity by machine learning variable importance techniques
Authors: Marcos-Pasero Helena , Colmenarejo Gonzalo , Aguilar-Aguilar Elena , Ramírez de Molina Ana , Reglero Guillermo , Loria-Kohen Viviana
Published: January 2021

The increased prevalence of childhood obesity is expected to translate in the near future into a concomitant soaring of multiple cardio-metabolic diseases. Obesity has a complex, multifactorial etiology, that includes multiple and multidomain potential risk factors: genetics, dietary and physical activity habits, socio-economic environment, lifestyle, etc. In addition, all these factors are expected to exert their influence through a specific and especially convoluted way during childhood, given the fast growth along this period. Machine Learning methods are the appropriate tools to model this complexity, given their ability to cope with high-dimensional, non-linear data. Here, we have analyzed by Machine Learning a sample of 221 children (6–9 years) from Madrid, Spain. Both Random Forest and Gradient Boosting Machine models have been derived to predict the body mass index from a wide set of 190 multidomain variables (including age, sex, genetic polymorphisms, lifestyle, socio-economic, diet, exercise, and gestation ones). A consensus relative importance of the predictors has been estimated through variable importance measures, implemented robustly through an iterative process that included permutation and multiple imputation. We expect this analysis will help to shed light on the most important variables associated to childhood obesity, in order to choose better treatments for its prevention.
Functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells
Authors: Cojocaru Florentina , Şelescu Tudor , Domocoş Dan , Măruţescu Luminiţa , Chiritoiu Gabriela , Chelaru Nicoleta-Raluca , Dima Simona , Mihăilescu Dan , Babes Alexandru , Cucu Dana
Published: January 2021

The transient receptor potential ankyrin type 1 (TRPA1) channel belongs to the TRP superfamily of ion channels. TRPA1 is a membrane protein with multiple functions able to respond to noxious stimuli, reactive oxygen species, inflammatory cytokines or pungent substances, and it participates in pain signalling, taste, inflammation and various steps of the tumorigenic process. To date, no reports have addressed the expression and function of TRPA1 in pancreatic ductal adenocarcinoma (PDAC) cells. This work reports the endogenous expression of TRPA1 channels in human pancreatic adenocarcinoma cell lines and provides insights into the function of the TRPA1 protein in the Panc-1 cell line. This study reports that cell lines isolated from PDAC patients had different levels of TRPA1 expression. The channel activity in Panc-1 cells, as assessed with electrophysiological (whole-cell patch clamp) and microfluorimetry methods, showed that non-selective cationic currents were activated by allyl isothiocyanate (AITC) in Panc-1 cells and inhibited by the selective TRPA1 antagonist A-967079. The current elicited by the specific agonist was associated with a robust increase in intracellular Ca2+. Furthermore, siRNA-induced downregulation of TRPA1 enhanced cell migration in the wound healing assay, indicating a possible role of ion channels independent from pore function. Finally, TRPA1 activation changed the cell cycle progression. Taken together, these results support the idea of channel-dependent and independent role for TRPA1 in tumoral processes.