bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with the time to transition from suicidal ideation to suicide plans and attempts in the Australian general population
Authors: Sunderland Matthew , Batterham Philip J. , Calear Alison L. , Chapman Cath , Slade Tim
Published: April 2021

Background

Suicide plans and attempts rarely occur without prior suicidal ideation but are hard to predict. Early intervention efforts need to focus on subgroups of the population who are more likely to transition from ideation to suicidal plans and attempts. The current study utilised data from a large nationally representative sample to investigate the time taken to transition and the demographic and mental health correlates of transitioning to suicidal plans and attempts among those with suicidal ideation.

Methods

Data were from 1237 Australians aged 16–85 years who reported suicidal thoughts at some point in their life. Discrete time survival analysis was used to retrospectively examine the time in years and correlates of transitioning from suicidal ideation to suicide plans and suicide attempt.

Results

The majority of those who transitioned to suicide plans or attempts typically did so within 2 years of first experiencing suicidal ideation. Several factors were independently associated with increased speed to transition, including alcohol use disorder, drug use disorder, major depressive episode, obsessive compulsive disorder, sexual minority status, and non-urban location. Older age, being male, older age of first ideation and greater family support were associated with a slower transition.

Conclusion

The current study suggests that pre-existing mental or substance use disorders, particularly drug use disorder, as well as sexual minority status, sex and greater family support play an important role in the transition from suicidal ideation to plans or attempts. These results highlight the potential importance of suicide prevention programs that aim to improve social connectedness.
Association of family history of schizophrenia and clinical outcomes in individuals with eating disorders
Authors: Zhang Ruyue , Kuja-Halkola Ralf , Birgegård Andreas , Larsson Henrik , Lichtenstein Paul , Bulik Cynthia M. , Bergen Sarah E.
Published: April 2021

Background

Familial co-aggregation studies of eating disorders (EDs) and schizophrenia reveal shared genetic and environment factors, yet their etiological and clinical relationship remains unclear. We evaluate the influence of schizophrenia family history on clinical outcomes of EDs.

Methods

We conducted a cohort evaluation of the association between family history of schizophrenia and ED clinical features, psychiatric comorbidities, and somatic and mental health burden in individuals born in Sweden 1977–2003 with anorexia nervosa (AN) or other EDs (OED: bulimia nervosa, binge-eating disorder, and ED not otherwise specified).

Results

Of 12 424 individuals with AN and 20 716 individuals with OED, 599 (4.8%) and 1118 (5.4%), respectively, had a family history of schizophrenia (in up to third-degree relatives). Among individuals with AN, schizophrenia in first-degree relatives was significantly associated with increased comorbid attention-deficit/hyperactivity disorder (ADHD) [HR(95% CI) 2.26 (1.27–3.99)], substance abuse disorder (SUD) [HR (95% CI) 1.93 (1.25–2.98)], and anxiety disorders [HR (95% CI) 1.47 (1.08–2.01)], but higher lowest illness-associated body mass index (BMI) [1.14 kg/m2, 95% CI (0.19–2.10)]. Schizophrenia in any relative (up to third-degree) in AN was significantly associated with higher somatic and mental health burden, but lower ED psychopathology scores [−0.29, 95% CI (−0.54 to −0.04)]. Schizophrenia in first-degree relatives in individuals with OED was significantly associated with increased comorbid ADHD, obsessive-compulsive disorder, SUD, anxiety disorders, somatic and mental health burden, and suicide attempts.

Conclusions

We observed different patterns of ED-related outcomes, psychiatric comorbidity, and illness burden in individuals with EDs with and without family histories of schizophrenia and provide new insights into the diverse manifestations of EDs.
Multispecialty Interprofessional Team Memory Clinics: Enhancing Collaborative Practice and Health Care Providers’ Experience of Dementia Care
Authors: Lee Linda , Molnar Frank , Hillier Loretta M. , Patel Tejal , Slonim Karen
Published: April 2021

This study explored whether working within Multispecialty INterprofessional Team (MINT) memory clinics has an impact on health care professionals’ perceptions of the challenges, attitudes, and level of collaboration associated with providing dementia care. Surveys were completed by MINT memory clinic members pre- and 6-months post-clinic launch. A total of 228 pre-and-post-training surveys were matched for analysis. After working in the MINT memory clinics for 6 months, there were significant reductions in mean ratings of the level of challenge associated with various aspects of dementia care, and significant increases in the frequency with which respondents experienced enthusiasm, inspiration, and pride in their work in dementia care and in ratings of the extent of collaboration for dementia care. This study provides some insights into the effect of collaborative, interprofessional approaches on health care professionals’ perceptions of the challenges and attitudes associated with providing dementia care and level of collaboration with other health professionals.
Desiccation tolerance and sensitivity of selected tropical montane species in Sri Lanka
Authors: Athugala Yasoja S. , Gehan Jayasuriya K. M. G. , Gunaratne A. M. T. A. , Baskin Carol C.
Published: April 2021

Although the level of seed desiccation sensitivity (LSDS) may have an impact on plant species conservation, information is available for <10% of tropical angiosperms. A study was conducted to assess the LSDS of 28 tropical montane species in Sri Lanka. Seeds were extracted from freshly collected fruits. Initial weight was recorded, and thousand seed weight (TSW) was calculated. Seed moisture content (MC) was determined. LSDS was determined using seed desiccation experiments and predicted using the TSW–MC criterion. Seed storage behaviour was predicted using LSDS and storage data and using a model based on phylogenetic affiliation. The relationship between LSDS and seed dormancy, life form and forest strata was evaluated. Fresh seeds of only 12 species germinated to >80%. Although seeds of the other species had >80% viability, only 0–70% germinated due to dormancy. Seeds of five species had MC <15%, indicating desiccation tolerance (DT). Seeds of 12 species lost viability after desiccation, indicating desiccation sensitivity (DS). Seeds of Ardisia missionis, Psychotria gartneri and Psychotria nigra remained viable after desiccation, showing DT. Seeds of 17 species were DS and those of 11 species DT. The TSW of four species was >500 g. Thus, seeds of other species were predicted to be DT by the TSW–MC criterion. A relationship was identified between LSDS and the forest strata of the species. More canopy species produced DS than DT seeds. Since seeds of most of the studied species were DS, these species may be threatened due to prolonged droughts predicted for the region due to climate change.
Supporting the Mental Health and Well-Being of First Responders from Career to Retirement: A Scoping Review
Authors: Smith Erin , Dean Greg , Holmes Lisa
Published: April 2021

Introduction:

First responders are at greater risk of mental ill health and compromised well-being compared to the general population. It is important to identify strategies that will be effective in supporting mental health, both during and after the first responder’s career.

Methods:

A scoping review was conducted using the PubMed database (1966 to October 1, 2020) and the Google Scholar database (October 1, 2020) using relevant search terms, truncation symbols, and Boolean combination functions. The reference lists of all relevant publications were also reviewed to identify further publications.

Results:

A total of 172 publications were retrieved by the combined search strategies. Of these, 56 met the inclusion criteria and informed the results of this overview paper. These publications identified that strategies supporting first responder mental health and well-being need to break down stigma and build resilience. Normalizing conversations around mental health is integral for increasing help-seeking behaviors, both during a first responder’s career and in retirement. Organizations should consider the implementation of both pre-retirement and post-retirement support strategies to improve mental health and well-being.

Conclusion:

Strategies for supporting mental health and well-being need to be implemented early in the first responder career and reinforced throughout and into retirement. They should utilize holistic approaches which encourage “reaching in” rather than placing an onus on first responders to “reach out” when they are in crisis.
Regional differences in the impact of the COVID-19 pandemic on food sufficiency in California, April–July 2020: implications for food programmes and policies
Authors: Blumenberg Evelyn , Pinski Miriam , Nhan Lilly A , Wang May C
Published: April 2021

Objective:

To evaluate regional differences in factors associated with food insufficiency during the initial months of the COVID-19 pandemic among three major metropolitan regions in California, a state with historically low participation rates in the Supplementation Nutrition Assistance Program, the nation’s largest food assistance programme.

Design:

Analysis of cross-sectional data from phase 1 (23 April–21 July 2020) of the US Census Household Pulse Survey, a weekly national online survey.

Setting:

California, and three Californian metropolitan statistical areas (MSA), including San Francisco–Oakland–Berkeley, Los Angeles–Long Beach–Anaheim and Riverside–San Bernardino–Ontario MSA.

Participants:

Adults aged 18 years and older living in households.

Results:

Among the three metropolitan areas, food insufficiency rates were lowest in the San Francisco–Oakland–Berkeley MSA. Measures of disadvantage (e.g., having low-income, being unemployed, recent loss of employment income and pre-pandemic food insufficiency) were widely associated with household food insufficiency. However, disadvantaged households in the San Francisco Bay Area, the area with the lowest poverty and unemployment rates, were more likely to be food insufficient compared with those in the Los Angeles–Long Beach–Anaheim and Riverside–San Bernardino–Ontario MSA.

Conclusions:

Food insufficiency risk among disadvantaged households differed by region. To be effective, governmental response to food insufficiency must address the varied local circumstances that contribute to these disparities.
The olfactory system: the remote-sensing arm of the immune system
Authors: Tizard Ian , Skow Loren
Published: April 2021

Odors may be pleasant or unpleasant and in practice, pleasant odors are attractive while unpleasant odors are repellent. However, an odor that is noxious to one species may be attractive to another. Plants, predators, and pathogens may enhance their transmission by manipulating these signals. This may be especially significant when odors attract arthropod disease vectors. Odor detection may also be important in small prey species for evasion of macropredators such as large carnivores. Conversely, pleasant odors may identify family members, parents, or sexual partners. They may also generate signals of good health or fitness and contribute to the process of mate selection. In this review, we seek to integrate these odor-driven processes into a coherent pattern of behaviors that serve to complement the innate and adaptive immune systems. It may be considered the ‘behavioral immune system’.
Ontological Appropriation: Boulez and Artaud
Authors: MENDELSSOHN EDMUND
Published: April 2021

This article examines the lessons that Pierre Boulez learned about sound from Antonin Artaud, suggesting that Boulez's ideas about musical writing (écriture) took shape as the composer imagined and appropriated forms of non-European expression. Boulez sometimes acknowledged the influence of ‘extra-European’ sounds in his music, but also insisted that music should not be a ‘simple ethnographic reconstruction’. Artaud, who explicitly ‘reconstructed’ the ethnographic other in a 1947 radio broadcast, will become my foil to show how Boulez's philosophy of writing hinged on an East–West dualism. I follow Boulez to South America with the Compagnie Renaud-Barrault to suggest that he took cues from Afro-Bahian Candomblé when he wrote Le Marteau sans maître. The conclusion reflects on the lessons that Boulez and Artaud might teach us about sound; namely, that recent musicological claims on behalf of the ontology of sound have modernist origins.
Depressive Symptoms are Associated with low Serotonin Levels in Plasma but are not 5–HTTLPR Genotype Dependent in Older Adults
Authors: Trujillo-Hernández Pedro Enrique , Sáenz-Galindo Aide , Saucedo-Cárdenas Odila , Villarreal-Reyna María de los Ángeles , Salinas-Santander Mauricio Andrés , Carrillo-Cervantes Ana Laura , Torres-Obregón Reyna , Esparza-González Sandra Cecilia
Published: April 2021

Depressive symptoms are diagnosed by physicians using scales but their pathophysiology is unclear. Low serotonin (5–HT) levels play an important role in depression, and the 5–HT transporter (5–HTT) is an important regulator of plasma serotonin levels and reuptake. Additionally, the 5–HTT gene-linked polymorphic region (5–HTTLPR) is associated with depression. The aim was to clarify the roles of plasma serotonin levels in plasma and the 5HTTPLR polymorphism in depressive symptoms in older adults. A total of 84 older adult participants were evaluated. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale of 20 items (CESD–20). The plasma serotonin levels were determined by ELISA, and the 5–HTTLPR genotype was analyzed by PCR. Depressive symptoms were present in 39.3% (N = 33) of the participants. The median plasma serotonin level was 204.34 ng/mL (SD = 93.88). A significant correlation was found between the CESD–20 scale and plasma serotonin levels (r = –.256; p = .019). Low serotonin levels were associated with the presence of depressive symptoms (p = .001). The 5–HTTLPR analysis showed that of the 84 older adults, 35.7% had the SS genotype, 10.7% had the LL genotype, and 53.6% were heterozygous. The 5–HTTLPR polymorphism was not associated with depressive symptoms (p = .587) and plasma serotonin levels (p = 0.391). Depressive symptoms correlate with low serotonin levels in plasma, but not with the 5–HTTLPR polymorphism in older Mexican adults.
Surface Turbulence Reveals Riverbed Drag Coefficient
Authors: Branch R. A. , Horner‐Devine A. R. , Chickadel C. C. , Talke S. A. , Clark D. , Jessup A. T.
Published: April 2021

Flow in rivers and the coastal ocean is controlled by the frictional force exerted on the water by riverbed or seabed roughness. The frictional force is typically characterized by a drag coefficient Cd, which is estimated from bulk measurements and often assumed constant. Here, we demonstrate a relationship between bed roughness and water surface turbulence that can be used to make remote estimates of Cd. We observe that regions with larger bed roughness result in greater turbulent kinetic energy (TKE), which is transported upward by river boils to the water surface. We present a relationship between surface TKE and Cd, and validate this relationship by comparing remotely sensed estimates of Cd to those from in situ measurements. Thus, our results provide an approach for estimating bottom roughness and Cd based entirely on remotely sensed data, including their spatial variability, which can improve modeling of river discharge and morphodynamics in data‐poor regions.
Simultaneous Observation of Two Isolated Proton Auroras at Subauroral Latitudes by a Highly Sensitive All‐Sky Camera and Van Allen Probes
Authors: Nakamura Kohki , Shiokawa Kazuo , Otsuka Yuichi , Shinbori Atsuki , Miyoshi Yoshizumi , Connors Martin , Spence Harlan , Reeves Geoff , Funsten Herbert O. , MacDowall Robert , Smith Charles , Wygant John , Bonnell John
Published: April 2021

Isolated proton auroras (IPAs) appearing at subauroral latitudes are generated by energetic protons precipitating from the magnetosphere through interaction with electromagnetic ion cyclotron (EMIC) waves. An IPA thus indicates the spatial scale and temporal variation of wave‐particle interactions in the magnetosphere. In this study, a unique event of simultaneous ground and magnetospheric satellite observations of two IPAs were conducted on March 16, 2015, using an all‐sky imager at Athabasca, Canada and Van Allen Probes. The Van Allen Probes observed two isolated EMIC waves with frequencies of ∼1 and 0.4 Hz at L ≈ 5.0 when the satellite footprint crossed over the two IPAs. This suggests that the IPAs were caused by localized EMIC waves. Proton flux at 5–20 keV increased locally when the EMIC waves appeared. Electron flux at energies below ∼500 eV also increased. Temperature anisotropy of the energetic protons was estimated at 1.5–2.5 over a wide L‐value range of 3.0–5.2. Electron density gradually decreased from L = 3.5 to 5.4, suggesting that the EMIC wave at L ≈ 5.0 was located in the gradual plasmapause. From these observations, we conclude that the localized IPAs and associated EMIC waves took place because of localized enhancement of energetic proton flux and plasma density structure near the plasmapause. The magnetic field observed by the satellite showed small variation during the wave observation, indicating that the IPAs were accompanied by the weak field‐aligned current.
Impacts of Horizontal Resolution on Global Data Assimilation of Satellite Measurements for Tropospheric Chemistry Analysis
Authors: Sekiya Takashi , Miyazaki Kazuyuki , Ogochi Koji , Sudo Kengo , Takigawa Masayuki , Eskes Henk , Boersma K. Folkert
Published: April 2021

We present the results from a global 0.56°‐resolution chemical data assimilation that integrates satellite observations of ozone, NO2, CO, HNO3, and SO2 from OMI, GOME‐2, SCIAMACHY, TES, MOPITT, and MLS. The assimilation is based on an ensemble Kalman filter technique and simultaneously optimizes ozone precursor emissions and concentrations of various species. The data assimilation at 0.56° resolution reduced model errors against independent surface, aircraft, and ozonesonde observations, which was larger than at coarser resolutions for many cases. By the data assimilation, surface model errors over major polluted regions were reduced by 33%–75% for NO2 and by 15%–18% for ozone. Agreements against assimilated observations for NO2 were improved using the data assimilation at 0.56° resolution by a factor of 1.5–3 compared to 2.8° resolution over major polluted regions. The estimated global total NOx emission over medium and strong source areas were smaller by 15% at 0.56° resolution than at 2.8° resolution associated with resolving small‐scale transport and chemistry processes, while 2%–26% smaller emissions were found for regional total emissions over Europe, the United States, China, India, and South Africa, with larger differences over megacities such as Los Angeles (−41%). The estimated ship emissions were 5%–7% smaller at 0.56° resolution over the Pacific and Atlantic. The 0.56°‐resolution data assimilation provides globally consistent analyses of the emissions and concentrations on a megacity scale, which benefit studies on air quality and its impact on human health at various spatial scales over different regions of the world.
Modeling the Geomagnetic Response to the September 2017 Space Weather Event Over Fennoscandia Using the Space Weather Modeling Framework: Studying the Impacts of Spatial Resolution
Authors: Dimmock A. P. , Welling D. T. , Rosenqvist L. , Forsyth C. , Freeman M. P. , Rae I. J. , Viljanen A. , Vandegriff E. , Boynton R. J. , Balikhin M. A. , Yordanova E.
Published: April 2021

We must be able to predict and mitigate against geomagnetically induced current (GIC) effects to minimize socio‐economic impacts. This study employs the space weather modeling framework (SWMF) to model the geomagnetic response over Fennoscandia to the September 7–8, 2017 event. Of key importance to this study is the effects of spatial resolution in terms of regional forecasts and improved GIC modeling results. Therefore, we ran the model at comparatively low, medium, and high spatial resolutions. The virtual magnetometers from each model run are compared with observations from the IMAGE magnetometer network across various latitudes and over regional‐scales. The virtual magnetometer data from the SWMF are coupled with a local ground conductivity model which is used to calculate the geoelectric field and estimate GICs in a Finnish natural gas pipeline. This investigation has lead to several important results in which higher resolution yielded: (1) more realistic amplitudes and timings of GICs, (2) higher amplitude geomagnetic disturbances across latitudes, and (3) increased regional variations in terms of differences between stations. Despite this, substorms remain a significant challenge to surface magnetic field prediction from global magnetohydrodynamic modeling. For example, in the presence of multiple large substorms, the associated large‐amplitude depressions were not captured, which caused the largest model‐data deviations. The results from this work are of key importance to both modelers and space weather operators. Particularly when the goal is to obtain improved regional forecasts of geomagnetic disturbances and/or more realistic estimates of the geoelectric field.
Linking Flood Frequency With Mesoscale Convective Systems in the US
Authors: Hu Huancui , Feng Zhe , Leung Lai‐Yung Ruby
Published: April 2021

Mesoscale convective systems (MCSs) with larger rain areas and higher rainfall intensity than non‐MCS events can produce severe flooding. Flooding occurrences associated with MCS and non‐MCS rainfall in the US east of 110°W are examined by linking a high‐resolution MCS data set and reported floods in the warm season (April‐August) between 2007 and 2017. MCSs account for the majority of slow‐rising and hybrid floods, while non‐MCS rainfall explains about half of flash floods in July and August as individual thunderstorms occur frequently in the Rocky Mountains and Appalachian Mountains. The event‐total rainfall area of MCSs is the dominant factor of flood occurrences: MCSs with greater rainfall areas tend to produce more floods. While not related to flood frequency, propagating MCSs tend to produce flash floods with longer durations. These established links can improve our confidence in interpreting flood risks and their future changes due to changes in MCS characteristics with warming.
Marginal Instability Within Internal Solitary Waves
Authors: Chang Ming‐Huei
Published: April 2021

High‐resolution observations of the currents, hydrography, and turbulence within internal solitary waves (ISWs) reveal Kelvin‐Helmholtz (KH) billows and breaking waveforms occurring in the lower periphery and in the trailing edges, respectively, of the wave cores. Marginal instability (MI) is evident in wave cores, where the probability distribution of the Richardson number Ri, fluctuates around 0.25. The critical value for the occurrence of KH instability in ISWs is evidently 0.25, the canonical criterion of a parallel stratified shear flow. When Ri > 0.25, the turbulent diffusivity Κρ remains O (10−3) m2 s−1 with a standard deviation of one order. When Ri crosses the critical value, the logarithmic turbulent diffusivity linearly increases with a logarithmic reduction in Ri to smooth the velocity and density differences so that Ri is ultimately restored to >0.25. Therefore, the processes of MI cycling preserve ISWs against breakdowns resulting from the uninterrupted growth of KH instability.
Investigating the Moon's Interaction With the Terrestrial Magnetotail Lobe Plasma
Authors: Liuzzo Lucas , Poppe Andrew R. , Halekas Jasper S. , Simon Sven , Cao Xin
Published: April 2021

We present observations of the Moon's plasma interaction in Earth's magnetotail lobes by the ARTEMIS mission, and compare these to hybrid model results to constrain the global properties of the lunar electromagnetic environment. We identify, for the first time in the magnetotail lobes, a low‐energy wake extending multiple lunar radii downstream of the Moon along the ambient flow direction. This wake is tilted out of the lunar optical shadow, allowing for detection of the otherwise unobservable cold ambient magnetospheric plasma. Similar eclipse encounters may provide additional opportunities to measure this low‐energy plasma potentially originating from the terrestrial ionosphere. We find lunar ionospheric outflow extending multiple Moon radii downstream that generates asymmetries in the Moon's plasma environment and shares characteristics with the plasma interactions of Rhea, Tethys, and Dione. The extensive ARTEMIS data set may therefore provide additional insights into the plasma environments near moons of the outer solar system.
Ionospheric Plasma Fluctuations Induced by the NWC Very Low Frequency Signal Transmitter
Authors: Ivarsen Magnus F. , Park Jaeheung , Jin Yaqi , Clausen Lasse B. N.
Published: April 2021

The Australian NWC (North West Cape) signal transmitter is known to strongly interfere with the topside ionosphere. We analyze 456 conjunctions between Swarm A, B and NWC, in addition to 58 conjunctions between NorSat‐1 and NWC. The in‐situ measurements provided by these satellites include the 16 Hz Swarm Advanced Plasma Density data set, and the novel 1,000 Hz plasma density measurements from the m‐NLP system aboard NorSat‐1. We subject the data to a detailed PSD analysis and subsequent superposed epoch analysis. This allows us to present comprehensive statistics of the NWC‐induced plasma fluctuations, both their scale‐dependency, and their climatology. The result should be seen in the context of VLF signal transmitter‐induced plasma density fluctuations, where we find counter‐evidence for the existence of turbulent structuring induced by the NWC transmitter.
Anti-tumor activity of a novel proteasome inhibitor D395 against multiple myeloma and its lower cardiotoxicity compared with carfilzomib
Authors: Shen Xuxing , Wu Chao , Lei Meng , Yan Qing , Zhang Haoyang , Zhang Lina , Wang Xueyuan , Yang Ye , Li Jianyong , Zhu Yongqiang , Chen Lijuan
Published: April 2021

Carfilzomib, a second-generation proteasome inhibitor, has significantly improved the survival rate of multiple myeloma (MM) patients, but its clinical application is still restricted by drug resistance and cardiotoxicity. Here, we identified a novel proteasome inhibitor, D395, and assessed its efficacy in treating MM as well as its cardiotoxicity at the preclinical level. The activities of purified and intracellular proteasomes were measured to determine the effect of D395 on the proteasome. CCK-8 and flow cytometry experiments were designed to evaluate the effects of D395 on cell growth and apoptosis. The effects of D395 and carfilzomib on serum enzyme activity, echocardiography features, cardiomyocyte morphology, and hERG channels were also compared. In our study, D395 was highly cytotoxic to MM cell lines and primary MM cells but not normal cells, and it was well tolerated in vivo. Similar to carfilzomib, D395 inhibited osteoclast differentiation in a dose-dependent manner. In particular, D395 exhibited lower cardiotoxicity than carfilzomib in all experiments. In conclusion, D395 is a novel irreversible proteasome inhibitor that has remarkable anti-MM activity and mild cardiotoxicity in vitro and in vivo.
Bruton’s tyrosine kinase regulates gut immune homeostasis through attenuating Th1 response
Authors: Guan Di , Wang Zixi , Huo Jianxin , Xu Shengli , Lam Kong-Peng
Published: April 2021

Inflammatory bowel disease (IBD) is driven by multiple genetic and environmental risk factors. Patients with mutations in Bruton’s tyrosine kinase (BTK) is known to manifest high prevalence of intestinal disorders including IBD. Although BTK mediates the signaling of various immune receptors, little is known how BTK maintains the homeostasis of the gut immune system. Here, we show that BTK-deficiency promotes IBD progression in a mouse model of colitis. Interestingly, the increased colitis susceptibility of BTK-deficient mice is not caused by gut microbiota changes but rather arises from enhanced pro-inflammatory Th1 response. More importantly, we find the heightened Th1 response in BTK-deficient mice to result from both T cell-extrinsic and -intrinsic mechanisms. BTK-deficient dendritic cells secret elevated levels of the Th1-polarizing cytokine IL-12 and BTK-deficient T cells are inherently more prone to Th1 differentiation. Thus, BTK plays critical roles in maintaining gut immune homeostasis and preventing inflammation via regulating T-cell polarization.
Permissive effect of GSK3β on profibrogenic plasticity of renal tubular cells in progressive chronic kidney disease
Authors: Chen Bohan , Wang Pei , Liang Xianhui , Jiang Chunming , Ge Yan , Dworkin Lance D. , Gong Rujun
Published: April 2021

Renal tubular epithelial cells (TECs) play a key role in renal fibrogenesis. After persistent injuries that are beyond self-healing capacity, TECs will dedifferentiate, undergo growth arrest, convert to profibrogenic phenotypes, and resort to maladaptive plasticity that ultimately results in renal fibrosis. Evidence suggests that glycogen synthase kinase (GSK) 3β is centrally implicated in kidney injury. However, its role in renal fibrogenesis is obscure. Analysis of publicly available kidney transcriptome database demonstrated that patients with progressive chronic kidney disease (CKD) exhibited GSK3β overexpression in renal tubulointerstitium, in which the predefined hallmark gene sets implicated in fibrogenesis were remarkably enriched. In vitro, TGF-β1 treatment augmented GSK3β expression in TECs, concomitant with dedifferentiation, cell cycle arrest at G2/M phase, excessive accumulation of extracellular matrix, and overproduction of profibrotic cytokines like PAI-1 and CTGF. All these profibrogenic phenotypes were largely abrogated by GSK3β inhibitors or by ectopic expression of a dominant-negative mutant of GSK3β but reinforced in cells expressing the constitutively active mutant of GSK3β. Mechanistically, GSK3β suppressed, whereas inhibiting GSK3β facilitated, the activity of cAMP response element-binding protein (CREB), which competes for CREB-binding protein, a transcriptional coactivator essential for TGF-β1/Smad signaling pathway to drive TECs profibrogenic plasticity. In vivo, in mice with folic acid-induced progressive CKD, targeting of GSK3β in renal tubules via genetic ablation or by microdose lithium mitigated the profibrogenic plasticity of TEC, concomitant with attenuated interstitial fibrosis and tubular atrophy. Collectively, GSK3β is likely a pragmatic therapeutic target for averting profibrogenic plasticity of TECs and improving renal fibrosis.
MIR99AHG is a noncoding tumor suppressor gene in lung adenocarcinoma
Authors: Han Chencheng , Li Hong , Ma Zhifei , Dong Guozhang , Wang Qianyun , Wang Siwei , Fang Panqi , Li Xiang , Chen Hao , Liu Tongyan , Xu Lin , Wang Jie , Wang Jun , Yin Rong
Published: April 2021

Little is known about noncoding tumor suppressor genes. An effective way to identify these genes is by analyzing somatic copy number variation (CNV)-related noncoding genes. By integrated bioinformatics analyses of differentially expressed long noncoding RNAs (lncRNAs) and arm-level CNVs in lung adenocarcinoma (LUAD), we identified a potential antitumor gene, MIR99AHG, encoding lncRNA MIR99AHG as well as a miR-99a/let-7c/miR-125b2 cluster on chromosome 21q. All four of these transcripts were downregulated in LUAD tissues partly due to the copy number deletion of the MIR99AHG gene. Both MIR99AHG and miR-99a expression was positively correlated with the survival of LUAD patients. MIR99AHG suppressed proliferation and metastasis and promoted autophagy both in vitro and in vivo. Mechanistically, the interaction between MIR99AHG and ANXA2 could accelerate the ANXA2-induced ATG16L+ vesicle biogenesis, thus promoting phagophore assembly. Additionally, miR-99a targeted a well-known autophagy suppressor, mammalian target of rapamycin (mTOR), thereby synergistically promoting autophagy and postponing LUAD progression with MIR99AHG. In summary, MIR99AHG emerges as a noncoding tumor suppressor gene in LUAD, providing a new strategy for antitumor therapy.
Tumor suppressive role of mitochondrial sirtuin 4 in induction of G2/M cell cycle arrest and apoptosis in hepatitis B virus-related hepatocellular carcinoma
Authors: Huang Fung-Yu , Wong Danny Ka-Ho , Seto Wai-Kay , Mak Lung-Yi , Cheung Tan-To , Yuen Man-Fung
Published: April 2021

Hepatocellular carcinoma (HCC) is developed from uncontrolled cell growth after the malignant transformation of hepatocytes. The hepatitis B virus (HBV) X protein (HBx) has shown to induce cell cycle progression and hepatocarcinogenesis. A sub-fraction of HBx is localized in the mitochondria. Sirtuin 4 (SIRT4), a mitochondrial protein, has been demonstrated to play a tumor-suppressive role in many cancers, including HCC. However, little is known about the association between mitochondrial HBx and SIRT4 during hepatocarcinogenesis. We aimed to investigate the clinical significance and functional role of SIRT4 in HBV-related HCC. SIRT4 expression was significantly lower in the HCC tissues collected from 30 patients with HBV-related HCC than in normal liver tissues from control patients (p < 0.0001). TCGA data analysis indicated that SIRT4 expression was also lower in patients with HBV infection than in those without, and SIRT4 levels were positively associated with better patient survival. Similarly, HCC cell lines had lower SIRT4 expression than normal liver cell lines (all p < 0.01). Among the HCC cell lines, those harbored HBV had a lower SIRT4 expression than those without HBV (p < 0.0001). In vitro experiments revealed that stable HBx transfection suppressed SIRT4 expression in both HepG2 and Huh7 cells (both p < 0.001). Ectopic SIRT4 overexpression alone could induce cellular senescence through arresting cell-cycle progression at G2/M, and inducing cell apoptosis in HCC cells. Mechanistically, SIRT4 upregulated cell-cycle governing genes p16 and p21 protein expression, suppressed CyclinB1/Cdc2 and Cdc25c which normally induce cell-cycle progression, and suppressed survivin to induce apoptosis. Our findings demonstrate the interaction between HBV and SIRT4 in the context of HCC. SIRT4 involves in G2/M DNA damage checkpoint control and genomic stability in hepatocarcinogenesis, which could be targeted for future anticancer strategies.
Strategies to improve photodynamic therapy efficacy by relieving the tumor hypoxia environment
Authors: Shen Zijun , Ma Qingming , Zhou Xinyu , Zhang Guimin , Hao Guizhou , Sun Yong , Cao Jie
Published: April 2021

Photodynamic therapy (PDT) is an emerging technology for tumor treatment in which photosensitizer (PS)-mediated light irradiation reduces oxygen, producing high levels of reactive oxygen species (ROS) that can cause vascular injury and effectively kill tumor cells. However, the naturally hypoxic tumor microenvironment is the main obstacle that hinders the photodynamic response in vivo and prevents its extensive application to tumor treatment. Moreover, PDT-mediated oxygen consumption further increases tumor hypoxia, potentially causing a variety of adverse consequences, such as angiogenesis, tumor invasion, and metastasis. To overcome these limitations caused by hypoxia, multiple strategies have been investigated, including the use of oxygen carriers and reactive oxygen supply materials, the regulation of tumor microenvironments, and multimodal therapy including PDT. In this review, we summarize the latest progress in the development of strategies to relieve tumor hypoxia for improved PDT efficacy and better therapeutic effects.
Multifunctional molybdenum disulfide flash memory using a PEDOT:PSS floating gate
Authors: Hong Seongin , Park Junwoo , Lee Jung Joon , Lee Sunjong , Yun Kyungho , Yoo Hocheon , Kim Sunkook
Published: April 2021

Two-dimensional transition metal dichalcogenide materials (TMDs), such as molybdenum disulfide (MoS2), have been considered promising candidates for future electronic applications owing to their electrical, mechanical, and optical properties. Here, we present a new concept for multifunctional MoS2 flash memory by combining a MoS2 channel with a PEDOT:PSS floating layer. The proposed MoS2 memory devices exhibit a switching ratio as high as 2.3 × 107, a large memory window (54.6 ± 7.80 V), and high endurance (>1,000 cycles). As the PEDOT:PSS film enables a low-temperature solution-coating process and mechanical flexibility, the proposed P-memory can be embedded on a polyimide substrate over a rigid silicon substrate, offering high mechanical endurance (over 1,000 cycle bending test). Furthermore, both MoS2 and PEDOT:PSS have a bandgap that is desirable in optoelectronic memory operation, where charge carriers are stored differently in the floating gate depending on light illumination. As a new application that combines photodiodes and memory functions, we demonstrate multilevel memory programming based on light intensity and color.
Dynamic regulation of DNA nanostructures by noncanonical nucleic acids
Authors: He Shiliang , Ge Zhilei , Zuo Xiaolei , Fan Chunhai , Mao Xiuhai
Published: April 2021

DNA nanostructures are among the most fascinating self-assembled nanostructures in diverse areas of science and technology, because of their nanoscale precision in biomolecule and nanoparticle organization. The implementation of dynamic and spatial regulation in structural morphology and hierarchical assembly upon specific external stimuli will greatly expand their applications in biocomputation, clinical diagnosis, and cancer therapy. Recently, noncanonical nucleic acids, particularly DNA triplexes, i-motifs, and G-quadruplexes, have become powerful tools for biosensing and mechanical switching. Developments in incorporating stimuli-responsive noncanonical nucleic acids into DNA nanostructures provide a promising approach to regulating the spatial organization and hierarchical assembly of DNA nanostructures. In this review, we briefly introduce recent progress in constructing DNA nanostructures with dynamic regulation of the structural transformation and programmable assembly pathways at the nanometer scale by noncanonical nucleic acids and discuss their potential applications and challenges.
Selective cell death in HIV-1-infected cells by DDX3 inhibitors leads to depletion of the inducible reservoir
Authors: Rao Shringar , Lungu Cynthia , Crespo Raquel , Steijaert Thijs H. , Gorska Alicja , Palstra Robert-Jan , Prins Henrieke A. B. , van Ijcken Wilfred , Mueller Yvonne M. , van Kampen Jeroen J. A. , Verbon Annelies , Katsikis Peter D. , Boucher Charles A. B. , Rokx Casper , Gruters Rob A. , Mahmoudi Tokameh
Published: April 2021

An innovative approach to eliminate HIV-1-infected cells emerging out of latency, the major hurdle to HIV-1 cure, is to pharmacologically reactivate viral expression and concomitantly trigger intracellular pro-apoptotic pathways in order to selectively induce cell death (ICD) of infected cells, without reliance on the extracellular immune system. In this work, we demonstrate the effect of DDX3 inhibitors on selectively inducing cell death in latent HIV-1-infected cell lines, primary CD4+ T cells and in CD4+ T cells from cART-suppressed people living with HIV-1 (PLWHIV). We used single-cell FISH-Flow technology to characterise the contribution of viral RNA to inducing cell death. The pharmacological targeting of DDX3 induced HIV-1 RNA expression, resulting in phosphorylation of IRF3 and upregulation of IFNβ. DDX3 inhibition also resulted in the downregulation of BIRC5, critical to cell survival during HIV-1 infection, and selectively induced apoptosis in viral RNA-expressing CD4+ T cells but not bystander cells. DDX3 inhibitor treatment of CD4+ T cells from PLWHIV resulted in an approximately 50% reduction of the inducible latent HIV-1 reservoir by quantitation of HIV-1 RNA, by FISH-Flow, RT-qPCR and TILDA. This study provides proof of concept for pharmacological reversal of latency coupled to induction of apoptosis towards the elimination of the inducible reservoir.
Mimicking associative learning using an ion-trapping non-volatile synaptic organic electrochemical transistor
Authors: Ji Xudong , Paulsen Bryan D. , Chik Gary K. K. , Wu Ruiheng , Yin Yuyang , Chan Paddy K. L. , Rivnay Jonathan
Published: April 2021

Associative learning, a critical learning principle to improve an individual’s adaptability, has been emulated by few organic electrochemical devices. However, complicated bias schemes, high write voltages, as well as process irreversibility hinder the further development of associative learning circuits. Here, by adopting a poly(3,4-ethylenedioxythiophene):tosylate/Polytetrahydrofuran composite as the active channel, we present a non-volatile organic electrochemical transistor that shows a write bias less than 0.8 V and retention time longer than 200 min without decoupling the write and read operations. By incorporating a pressure sensor and a photoresistor, a neuromorphic circuit is demonstrated with the ability to associate two physical inputs (light and pressure) instead of normally demonstrated electrical inputs in other associative learning circuits. To unravel the non-volatility of this material, ultraviolet-visible-near-infrared spectroscopy, X-ray photoelectron spectroscopy and grazing-incidence wide-angle X-ray scattering are used to characterize the oxidation level variation, compositional change, and the structural modulation of the poly(3,4-ethylenedioxythiophene):tosylate/Polytetrahydrofuran films in various conductance states. The implementation of the associative learning circuit as well as the understanding of the non-volatile material represent critical advances for organic electrochemical devices in neuromorphic applications.
Percolation on feature-enriched interconnected systems
Authors: Artime Oriol , De Domenico Manlio
Published: April 2021

Percolation is an emblematic model to assess the robustness of interconnected systems when some of their components are corrupted. It is usually investigated in simple scenarios, such as the removal of the system’s units in random order, or sequentially ordered by specific topological descriptors. However, in the vast majority of empirical applications, it is required to dismantle the network following more sophisticated protocols, for instance, by combining topological properties and non-topological node metadata. We propose a novel mathematical framework to fill this gap: networks are enriched with features and their nodes are removed according to the importance in the feature space. We consider features of different nature, from ones related to the network construction to ones related to dynamical processes such as epidemic spreading. Our framework not only provides a natural generalization of percolation but, more importantly, offers an accurate way to test the robustness of networks in realistic scenarios.
Magnetic Janssen effect
Authors: Thorens L. , Måløy K. J. , Bourgoin M. , Santucci S.
Published: April 2021

A pile of grains, even when at rest in a silo, can display fascinating properties. One of the most celebrated is the Janssen effect, named after the pioneering engineer who explained the pressure saturation at the bottom of a container filled with corn. This surprising behavior arises because of frictional interactions between the grains through a disordered network of contacts, and the vessel lateral walls, which partially support the weight of the column, decreasing its apparent mass. Here, we demonstrate control over frictional interactions using ferromagnetic grains and an external magnetic field. We show that the anisotropic pairwise interactions between magnetized grains result in a radial force along the walls, whose amplitude and direction is fully determined by the applied magnetic field. Such magnetic Janssen effect allows for the fine tuning of the granular column apparent mass. Our findings pave the way towards the design of functional jammed materials in confined geometries, via a further control of both their static and dynamic properties.
Fluid pressurisation and earthquake propagation in the Hikurangi subduction zone
Authors: Aretusini S. , Meneghini F. , Spagnuolo E. , Harbord C. W. , Di Toro G.
Published: April 2021

In subduction zones, seismic slip at shallow crustal depths can lead to the generation of tsunamis. Large slip displacements during tsunamogenic earthquakes are attributed to the low coseismic shear strength of the fluid-saturated and non-lithified clay-rich fault rocks. However, because of experimental challenges in confining these materials, the physical processes responsible for the coseismic reduction in fault shear strength are poorly understood. Using a novel experimental setup, we measured pore fluid pressure during simulated seismic slip in clay-rich materials sampled from the deep oceanic drilling of the Pāpaku thrust (Hikurangi subduction zone, New Zealand). Here, we show that at seismic velocity, shear-induced dilatancy is followed by pressurisation of fluids. The thermal and mechanical pressurisation of fluids, enhanced by the low permeability of the fault, reduces the energy required to propagate earthquake rupture. We suggest that fluid-saturated clay-rich sediments, occurring at shallow depth in subduction zones, can promote earthquake rupture propagation and slip because of their low permeability and tendency to pressurise when sheared at seismic slip velocities.
Three body photodissociation of the water molecule and its implications for prebiotic oxygen production
Authors: Chang Yao , Yu Yong , An Feng , Luo Zijie , Quan Donghui , Zhang Xia , Hu Xixi , Li Qinming , Yang Jiayue , Chen Zhichao , Che Li , Zhang Weiqing , Wu Guorong , Xie Daiqian , Ashfold Michael N. R. , Yuan Kaijun , Yang Xueming
Published: April 2021

The provenance of oxygen on the Earth and other planets in the Solar System is a fundamental issue. It has been widely accepted that the only prebiotic pathway to produce oxygen in the Earth’s primitive atmosphere was via vacuum ultraviolet (VUV) photodissociation of CO2 and subsequent two O atom recombination. Here, we provide experimental evidence of three-body dissociation (TBD) of H2O to produce O atoms in both 1D and 3P states upon VUV excitation using a tunable VUV free electron laser. Experimental results show that the TBD is the dominant pathway in the VUV H2O photochemistry at wavelengths between 90 and 107.4 nm. The relative abundance of water in the interstellar space with its exposure to the intense VUV radiation suggests that the TBD of H2O and subsequent O atom recombination should be an important prebiotic O2-production, which may need to be incorporated into interstellar photochemical models.
Vacuum brazing of Al2O3 and 3D printed Ti6Al4V lap-joints using high entropy driven AlZnCuFeSi filler
Authors: Sharma Ashutosh , Ahn Byungmin
Published: April 2021

In this work, we studied the brazing characteristics of Al2O3 and 3D printed Ti–6Al–4V alloys using a novel equiatomic AlZnCuFeSi high entropy alloy filler (HEAF). The HEAF was prepared by mechanical alloying of the constituent powder and spark plasma sintering (SPS) approach. The filler microstructure, wettability and melting point were investigated. The mechanical and joint strength properties were also evaluated. The results showed that the developed AlZnCuFeSi HEAF consists of a dual phase (Cu–Zn, face-centered cubic (FCC)) and Al–Fe–Si rich (base centered cubic, BCC) phases. The phase structure of the (Cu–Al + Ti–Fe–Si)/solid solution promises a robust joint between Al2O3 and Ti–6Al–4V. In addition, the joint interfacial reaction was found to be modulated by the brazing temperature and time because of the altered activity of Ti and Zn. The optimum shear strength reached 84 MPa when the joint was brazed at 1050 °C for 60 s. The results can be promising for the integration of completely different materials using the entropy driven fillers developed in this study.