bluuebunny/crossref_metadata_2025 huggingface dataset:
The Clinical and Cognitive Spectrum of Artery of Percheron Infarction: 1-Year Follow-Up
Authors: Çetin Fatma Ece , Kumral Emre , Dere Birgül
Published: September 2021

Objective:

Survivors of patients with artery of Percheron infarction (API) often have a prolonged and disabling form of cognitive impairment that remains insufficiently characterized. We aimed to examine the clinical and cognitive features of API in the short and long term after stroke.

Methods:

We reviewed 6400 patients with a first-ever stroke included in the Stroke Registry between 2011 and 2021. The diagnosis of API was based on clinical diagnosis and imaging confirmation. All patients underwent neuropsychological assessment at hospital stay and 1 year after stroke. A z-score of each patients’ cognitive test point was calculated, and a z-score inferior to 2 was considered as pathological.

Results:

Of the 10 patients enrolled, all had cognitive impairment, consciousness, and behavioral disorders at stroke onset. Six patients had pure bilateral thalamic involvement while four had bilateral thalamic and rostral midbrain involvement. At 12 months, 50% of patients had global mental state scores 2 SD below the population mean (z-score mean ± SD, −2.17 ± 0.4). Most of the prefrontal cortex cognitive processes including executive functions such as planning and cognitive control (z-score mean ± SD, −3.92 ± 0.3), processing speed (−4.42 ± 0.5), working memory (−3.97 ± 0.3) were severely impaired at stroke onset. Especially in patients with thalamic and rostral midbrain involvement, deficiencies in executive function (z-score mean ± SD, −2.60 ± 0.4), processing speed (−2.22 ± 0.5), working (−3.76 ± 0.4), and episodic memory (−2.23 ± 0.3) continued 12 months after stroke.

Conclusions:

The occlusion of the artery of Percheron results in severe behavioral and cognitive disorders in the short and long term after stroke.
Frequency–time analysis, low-rank reconstruction and denoising of turbulent flows using SPOD
Authors: Nekkanti Akhil , Schmidt Oliver T.
Published: September 2021

Four different applications of spectral proper orthogonal decomposition (SPOD) are demonstrated on large-eddy simulation data of a turbulent jet. These are: low-rank reconstruction, denoising, frequency–time analysis and prewhitening. We demonstrate SPOD-based flow-field reconstruction using direct inversion of the SPOD algorithm (frequency-domain approach) and propose an alternative approach based on projection of the time series data onto the modes (time-domain approach). We further present a SPOD-based denoising strategy that is based on hard thresholding of the SPOD eigenvalues. The proposed strategy achieves significant noise reduction while facilitating drastic data compression. In contrast to standard methods of frequency–time analysis such as wavelet transform, a proposed SPOD-based approach yields a spectrogram that characterises the temporal evolution of spatially coherent flow structures. A convolution-based strategy is proposed to compute the time-continuous expansion coefficients. When applied to the turbulent jet data, SPOD-based frequency–time analysis reveals that the intermittent occurrence of large-scale coherent structures is directly associated with high-energy events. This work suggests that the time-domain approach is preferable for low-rank reconstruction of individual snapshots, and the frequency-domain approach for denoising and frequency–time analysis.
Scale-invariant spins and tumbles in turbulence
Authors: Mathai Varghese
Published: September 2021

A Lagrangian perspective has yielded many new insights in our quest to reveal the intricacies of turbulent flows. Much of this progress has been possible by following the trajectories of idealised, inertialess objects (tracers) traversing through the flow. Their spins and tumbles provide a glimpse into the underlying local velocity gradients of the turbulent field. While it is known that the spinning and tumbling rates of anisotropic particles are modified in turbulence – compared with those in a random flow field – a quantitative explanation for this has remained elusive. Now, Pujara et al. (J. Fluid Mech., vol. 922, 2021, R6) have made an attempt to predict the split between spinning and tumbling rates by accessing the particle's alignment with the local vorticity. Their analysis of filtered turbulent fields reveals a Lagrangian scale invariance, whereby key quantities relating to the particle's rotational statistics are preserved from the dissipative to the integral scale.
The possible role of increased consumption of ultra-processed food products in the development of frailty: a threat for healthy ageing?
Authors: Mariath Aline Brandão , Machado Alisson Diego , Ferreira Letícia do Nascimento Maximiano , Ribeiro Sandra Maria Lima
Published: September 2021

Frailty, a multifactorial ageing-related syndrome characterised by reduced resistance to stressors and possibly associated with low-grade systemic inflammation, results in negative health outcomes and compromises healthy ageing. There is a growing body of evidence on the relationship between dietary habits, low-grade systemic inflammation and the risk of frailty. Consumption of dietary ultra-processed products (UPP) could negatively contribute to these conditions. In this article, we intend to (i) discuss the role that UPP might have on the development of frailty considering the inflammatory potential of this type of food and (ii) to raise awareness on deleterious effects of excess UPP intake in the development of adverse health outcomes, in particular, frailty and compromised healthy ageing. UPP are industrial formulations whose nutrient profile has been associated with inflammation and altered gut microbiota. Besides, diets with a greater presence of unprocessed foods and antioxidants have been linked to the reduction of oxidative stress and the expression of inflammatory biomarkers. Because inflammation is believed to be a contributing factor in the development of frailty, it is possible that UPP would contribute to the onset or increase of this condition. Importantly, the increasing consumption of UPP in younger populations might pose a greater risk to the development of compromised healthy ageing in the long term.
Riceberry rice (Oryza sativa L.) slows gastric emptying and improves the postprandial glycaemic response
Authors: Muangchan Nipaporn , Khiewvan Benjapa , Chatree Saimai , Pongwattanapakin Kitchaya , Kunlaket Nattinee , Dokmai Traiphop , Chaikomin Reawika
Published: September 2021

Postprandial glycaemia is a key determinant of overall glycaemic control. One mechanism by which dietary strategies can reduce postprandial glycaemic excursions is by slowing gastric emptying. This study aimed to evaluate the acute effect of ingesting riceberry rice (RR) compared with that of ingesting white rice (WR) on gastric emptying rate (GER), plasma glucose and glucose-regulating hormones, including insulin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), in healthy subjects. A randomised, open-label, within-subject, crossover study was performed in six healthy men. GER was measured by scintigraphy over 240 min, and plasma concentrations of glucose, insulin, GLP-1 and GIP were measured at multiple time points over 180 min. This study revealed that RR slows GER with a reduction in postprandial plasma glucose concentrations compared with WR. Plasma insulin and GLP-1 concentrations did not differ between RR and WR. However, plasma GIP concentrations were markedly increased after WR ingesting v. after RR ingestion. We conclude that RR attenuates postprandial glycaemia by slowing GER without altering plasma insulin or GLP-1. Plasma GIP concentrations are likely related to differences in GER and carbohydrate absorption. We propose that dietary fibre-enriched foods, including RR, could contribute to improvement in postprandial glycaemia via delayed gastric emptying.
Cognitive reserve as a moderator of outcomes in five clusters of first episode psychosis patients: a 10-year follow-up study of the PAFIP cohort
Authors: Ayesa-Arriola Rosa , de la Foz Victor Ortiz-García , Murillo-García Nancy , Vázquez-Bourgon Javier , Juncal-Ruiz María , Gómez-Revuelta Marcos , Suárez-Pinilla Paula , Setién-Suero Esther , Crespo-Facorro Benedicto
Published: September 2021

Background

Cognitive reserve (CR) has been associated with the development and prognosis of psychosis. Different proxies have been used to estimate CR among individuals. A composite score of these proxies could elucidate the role of CR at illness onset on the variability of clinical and neurocognitive outcomes.

Methods

Premorbid intelligence quotient (IQ), years of education and premorbid adjustment were explored as proxies of CR in a large sample (N = 424) of first-episode psychosis (FEP) non-affective patients. Clusters of patients were identified and compared based on premorbid, clinical and neurocognitive variables at baseline. Additionally, the clusters were compared at 3-year (N = 362) and 10-year (N = 150) follow-ups.

Results

The FEP patients were grouped into five CR clusters: C1 (low premorbid IQ, low education and poor premorbid) 14%; C2 (low premorbid IQ, low education and good premorbid adjustment) 29%; C3 (normal premorbid IQ, low education and poor premorbid adjustment) 17%; C4 (normal premorbid IQ, medium education and good premorbid adjustment) 25%; and C5 (normal premorbid IQ, higher education and good premorbid adjustment) 15%. In general, positive and negative symptoms were more severe in the FEP patients with the lowest CR at baseline and follow-up assessments, while those with high CR presented and maintained higher levels of cognitive functioning.

Conclusions

CR could be considered a key factor at illness onset and a moderator of outcomes in FEP patients. A high CR could function as a protective factor against cognitive impairment and severe symptomatology. Clinical interventions focused on increasing CR and documenting long-term benefits are interesting and desirable.
Assistive Technology Use among Older Adults with Vision Loss: A Critical Discourse Analysis of Canadian Newspapers
Authors: Fuchigami Katharine , McGrath Colleen , Bengall Jordana , Kim Stephanie , Rudman Debbie Laliberte
Published: September 2021

Low vision assistive devices are often positioned as enabling continued social participation and engagement by older adults in everyday activities; however, previous research suggests that the use of such technologies is restricted by various environmental factors. With little attention previously paid to the discursive environment, this critical discourse analysis critically examined how aging persons with vision loss and assistive technology (AT) were constructed and the occupational possibilities promoted and marginalized through technology use in six Canadian newspapers. In total, 7,289 articles were screened, 1,867 articles underwent a full-text review, and 51 articles were selected for data analysis. Results highlight four key discursive threads related to the framing of disability and AT, positioning of seniors with vision loss, and the ideals and occupations to be attained through AT, and point to the importance of re-configuring discourses addressing AT for seniors with vision loss to expand occupational possibilities and embrace collaborative design approaches.
Public Service Announcements and Promoting Face Masks During the COVID-19 Pandemic
Authors: Greene Steven , Hetherington Marc , Maxwell Rahsaan , Ryan Timothy J.
Published: September 2021

Wearing face masks to combat the spread of COVID-19 became a politicized and contested practice in the United States, largely due to misinformation and partisan cues from masking opponents. This article examines whether Public Service Announcements (PSAs) can encourage the use of face masks. We designed two PSAs: one describes the benefits of using face masks; the other uses a novel messenger (i.e., a retired US general) to advocate for them. We conducted two studies. First, we aired our PSAs on television and surveyed residents of the media market to determine if they saw the PSA and how they felt about wearing face masks. Second, we conducted a randomized experiment on a diverse national sample. Both studies suggest that exposure to our PSAs increased support for face masks and induced greater compliance with public health advice. These findings have implications for how governments might fight pandemics.
Translation and validation of the Child Three-Factor Eating Questionnaire (CTFEQr17) in French-speaking Canadian children and adolescents
Authors: Frappier Isabelle , Jacob Raphaëlle , Panahi Shirin , Larose David , Bryant Eleanor J , Chaput Jean-Philippe , Thivel David , Drapeau Vicky
Published: September 2021

Objective:

To translate and validate the Child Three-Factor Eating Questionnaire (CTFEQr17), assessing cognitive restraint (CR), uncontrolled eating (UE) and emotional eating (EE), among French-speaking Canadian young individuals.

Design:

Phase 1 comprised a translation and the evaluation of the comprehension of the questionnaire. Phase 2 comprised a confirmatory factor analysis (CFA), the evaluation of internal consistency (Cronbach’s α), test–retest reliability (intra-class correlation coefficients (ICC)) and construct validity, including correlations among the CTFEQr17 and Eating Attitudes Test (EAT-26), anthropometrics, dietary intake and diet quality.

Setting:

Primary and secondary schools, Québec City, Canada.

Participants:

Phases 1 and 2 included 20 (40 % boys, mean age 11·5 (sd 2·4) years) and 145 (48 % boys, mean age 11·0 (sd 1·9) years) participants, respectively.

Results:

Phase 1 resulted in the questionnaire to be used in Phase 2. In Phase 2, the CFA revealed that the seventeen item, three-factor model (CTFEQr17) provided an excellent fit. Internal consistency was good (Cronbach’s α: 0·81–0·90). Test–retest reliability was moderate to good (ICC = 0·59, (95 % CI 0·48, 0·70), ICC = 0·78, (95 % CI 0·70, 0·84), ICC = 0·50, (95 % CI 0·38, 0·62) for CR, UE and EE, respectively). CR correlated with EAT-26 score (r = 0·43, P < 0·0001). UE and EE correlated negatively with BMI Z-scores (r = −0;·26, P = 0·003; r = −0;·19, P = 0·03, respectively). CR correlated with the proportion of energy intake from protein and diet quality (r = 0·18, P = 0·04; r = 0·20, P = 0·02, respectively).

Conclusion:

The CTFEQr17 is suitable to use among French-speaking Canadian young individuals.
Effects of maternal controlled exercise on offspring adiposity and glucose tolerance
Authors: Platt Kristen M. , Przybylowski Jenna , Charnigo Richard J. , Ngo Tenlep Sara Y. , Reynolds Leryn J. , Pearson Kevin J.
Published: September 2021

While metabolic disorders such as obesity and diabetes are costly and deadly to the current population, they are also extremely detrimental to the next generation. Much of the current literature focuses on the negative impact of poor maternal choices on offspring disease, while there is little work examining maternal behaviors that may improve offspring health. Research has shown that voluntary maternal exercise in mouse models improves metabolic function in offspring. In this study, we hypothesized that controlled maternal exercise in a mouse model will effect positive change on offspring obesity and glucose homeostasis. Female mice were separated into three groups: home cage, sedentary, and exercise. The sedentary home cage group was not removed from the home cage, while the sedentary wheel group was removed from the cage and placed in an immobile wheel apparatus. The exercise group was removed from the home cage and run on the same wheel apparatus but with the motor activated at 5–10 m/min for 1 h/d prior to and during pregnancy. Offspring were subjected to oral glucose tolerance testing and body composition analysis. There was no significant difference in offspring glucose tolerance or body composition as a consequence of the maternal exercise intervention compared to the sedentary wheel group. There were no marked negative consequences of the maternal controlled exercise intervention. Further research should clarify the potential advantages of the controlled exercise model and improve experimental techniques to facilitate translation of this research to human applications.
A Quantitative Scaling Theory for Meridional Heat Transport in Planetary Atmospheres and Oceans
Authors: Gallet Basile , Ferrari Raffaele
Published: September 2021

The meridional temperature profile of the upper layers of planetary atmospheres is set through a balance between differential radiative heating by a nearby star, or by intrinsic heat fluxes emanating from the deep interior, and the redistribution of that heat across latitudes by turbulent flows. These flows spontaneously arise through baroclinic instability of the meridional temperature gradients maintained by the forcing. When planetary curvature is neglected, this turbulence takes the form of coherent vortices that mix the meridional temperature profiles. However, the curvature of the planet favors the emergence of Rossby waves and zonal jets that restrict the meridional wandering of the fluid columns, thereby reducing the mixing efficiency across latitudes. A similar situation arises in the ocean, where the baroclinic instability of zonal currents leads to enhanced meridional heat transport by a turbulent flow consisting of vortices and zonal jets. A recent scaling theory for the turbulent heat transport by vortices is extended to include the impact of planetary curvature, in the framework of the two‐layer quasi‐geostrophic beta‐plane model. This leads to a quantitative parameterization providing the meridional temperature profile in terms of the externally imposed heat flux in an idealized model of planetary atmospheres and oceans. In addition, it provides a quantitative prediction for the emergent criticality, that is, the degree of instability in a canonical model of planetary atmosphere or ocean.
Stress Field Estimation From S‐Wave Anisotropy Observed in Multi‐Azimuth Seismic Survey With Cabled Seafloor Seismometers Above the Nankai Trough Megathrust Zone, Japan
Authors: Kimura T. , Mikada H. , Araki E. , Kodaira S. , Miura S. , Takahashi N.
Published: September 2021

The spatial variation of azimuthal S‐wave phase velocity anisotropies caused by differential horizontal stress along the Nankai Trough was analyzed to understand the stress state of the overhung block of the forearc region, off Kii Peninsula, Japan. We conducted controlled‐source seismic surveys along the circumference of a 3 km radius circle centered at each seismometer of a cabled seafloor observatory installed in the Nankai subduction zone. We applied an anisotropy semblance method to estimate the orientation of fast and slow S‐wave velocities of shallow sediments and deep accretionary prism using the multi‐azimuth seismic dataset acquired at each seismometer location. The estimated orientations of fast S‐wave velocity are parallel to the convergent direction of the subducting place beneath the Kumano basin in the deeper accretionary prism while perpendicular to the convergent direction in the shallow sediments inside the Kumano basin. These fast S‐wave polarization orientations in shallow sediments show good agreement with horizontal maximum stress orientations estimated in situ borehole measurements in the observation area. We estimated the differential horizontal stress field in the Nankai Trough region from obtained S‐wave anisotropy using a simple crack model. Using this method, we first suggest the convergent‐parallel horizontal maximum compression in the deeper part of the accretionary prism above the locked portion. Assuming obtained S‐wave anisotropy is attributed to the tectonic loading by the subducting plate, these results suggest that the S‐wave azimuthal anisotropy measurements can be used to monitor the subsurface stress field as a function of time.
Impoundment‐Associated Hydro‐Mechanical Changes and Regional Seismicity Near the Xiluodu Reservoir, Southwestern China
Authors: Zhang Man , Ge Shemin , Yang Qiang , Ma Xiaodong
Published: September 2021

Four large hydropower stations have recently been built downstream the Jinsha River in Southwestern China with a strong regional tectonic activity background. There is widely felt seismicity since the impoundment of the Xiluodu and Xiangjiaba reservoirs, increasing the public concern in this region. We begin with a criticality analysis of the faults near these reservoirs to quantify their susceptibility to triggered seismicity. Then we focus on the Xiluodu reservoir to investigate the correlation between the impoundment and seismicity nearby. We analyze the spatio‐temporal distribution of seismicity near the Xiluodu reservoir, and identify the plausible rapid and delayed seismic response due to the impoundment. According to the impoundment record, we explicitly model the hydro‐mechanical changes due to diffusion and reservoir water load, that is, pore pressure, elastic stress, and the resulting Coulomb stress. Our results show that the pore pressure changes can reach a level that may trigger fault reactivation and consequently, seismicity nearby. The water load can also induce the positive Coulomb stress changes on faults, depending on the fault orientation, which is especially important for understanding the earthquakes that occurred shortly after the impoundment and at more than 10 km distance from the reservoir. The combination of these two effects can induce positive Coulomb stress change over a larger area, which overlaps the majority of the events after the impoundment, including two M5+ events. While the causal relationship between the impoundment and seismicity warrants further analysis, we hope to inform the regional seismic impact of impoundment with this timely study.
Seasonality of DOC Export From a Russian Subarctic Catchment Underlain by Discontinuous Permafrost, Highlighted by High‐Frequency Monitoring
Authors: Gandois L. , Tananaev N. I. , Prokushkin A. , Solnyshkin I. , Teisserenc R.
Published: September 2021

Intense climate change and permafrost degradation impact northern watersheds and ultimately organic carbon transfer from terrestrial to aquatic ecosystems. We investigated the contemporary dissolved organic carbon (DOC) dynamics in a northern catchment underlain by discontinuous permafrost (Graviyka River, northern Siberia), where historical meteorological and hydrological data are available since 1936. Mean annual air temperature (MAAT), in contrast to precipitation and discharge was found to show a significant increasing trend since 1950. Using in situ sensing of fluorescent dissolved organic matter (fDOM), we estimated DOC concentrations at a high temporal frequency (1h) during 3 years (2015–2018), and calculated annual specific fluxes of 5.2–5.5 g C m2 yr−1. High DOC concentrations (above 10 mg L−1) are sustained all year, exhibiting nearly chemostatic behavior. Nevertheless, the high‐frequency survey of DOC and other water parameters revealed the seasonality of DOC origin and pathways in the watershed. The spring freshet dominates the annual export (up to 80%), but summer and autumn floods can also contribute up to 9% and 8% respectively. The high‐frequency sampling was able to capture the specific dynamic of DOC concentration during spring flood (DOC peak preceding discharge, dilution during the spring freshet) and summer and autumn floods (contribution of DOC‐rich, low conductivity water). These observations suggest a significant contribution of organic‐rich water originating in peatlands, potentially from degrading palsas. The study demonstrates both that high‐frequency sampling is essential to capture key events for DOC export, and that more long‐term monitoring is urgently needed in these rapidly evolving watersheds.
Cascading Effects of Extreme Geohazards on Tenerife (Canary Islands)
Authors: López‐Saavedra Marta , Martí Joan , Rubio Jose Luis , Kelfoun Karim
Published: September 2021

Extreme geohazards (volcanic eruptions, earthquakes, landslides, and tsunamis) have the potential to inflict cascading effects whose associated risks are difficult to predict and prepare for. Thus, these events are generally not taken into account in hazard assessment. Anticipating the occurrence of such extreme events is thus key if our life‐styles are to remain safe and sustainable. Volcanic islands are often the source of complex successions of disastrous events, as is evident from any examination, for instance, of the geological record of regions such as Hawaii, the Canary Islands, Reunion and Indonesia. The island of Tenerife in the Canary Archipelago is an excellent example of where cascading extreme hazards have occurred several times in the past and could occur again in the future. A cascading sequence involving a caldera‐forming eruption, high‐magnitude seismicity, mega‐landslides and tsunamis occurred at least twice during the construction of this island. In order to understand the possible consequences of such processes if they were to reoccur, we simulated the extent and potential impact of a multiple, extreme geohazard episode similar to the last recorded one that took place on the island of Tenerife around 180 ka. The implications of such a disastrous succession of events are analyzed at local, regional and global scales, and the results obtained are discussed within the framework of disaster risk‐reduction policies.
A combination of PARP and CHK1 inhibitors efficiently antagonizes MYCN-driven tumors
Authors: Di Giulio Stefano , Colicchia Valeria , Pastorino Fabio , Pedretti Flaminia , Fabretti Francesca , Nicolis di Robilant Vittoria , Ramponi Valentina , Scafetta Giorgia , Moretti Marta , Licursi Valerio , Belardinilli Francesca , Peruzzi Giovanna , Infante Paola , Goffredo Bianca Maria , Coppa Anna , Canettieri Gianluca , Bartolazzi Armando , Ponzoni Mirco , Giannini Giuseppe , Petroni Marialaura
Published: September 2021

MYCN drives aggressive behavior and refractoriness to chemotherapy, in several tumors. Since MYCN inactivation in clinical settings is not achievable, alternative vulnerabilities of MYCN-driven tumors need to be explored to identify more effective and less toxic therapies. We previously demonstrated that PARP inhibitors enhance MYCN-induced replication stress and promote mitotic catastrophe, counteracted by CHK1. Here, we showed that PARP and CHK1 inhibitors synergized to induce death in neuroblastoma cells and in primary cultures of SHH-dependent medulloblastoma, their combination being more effective in MYCN amplified and MYCN overexpressing cells compared to MYCN non-amplified cells. Although the MYCN amplified IMR-32 cell line carrying the p.Val2716Ala ATM mutation showed the highest sensitivity to the drug combination, this was not related to ATM status, as indicated by CRISPR/Cas9-based correction of the mutation. Suboptimal doses of the CHK1 inhibitor MK-8776 plus the PARP inhibitor olaparib led to a MYCN-dependent accumulation of DNA damage and cell death in vitro and significantly reduced the growth of four in vivo models of MYCN-driven tumors, without major toxicities. Our data highlight the combination of PARP and CHK1 inhibitors as a new potential chemo-free strategy to treat MYCN-driven tumors, which might be promptly translated into clinical trials.
Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer
Authors: Ye Runyi , AiErken NiJiati , Kuang Xiaying , Zeng Huijuan , Shao Nan , Lin Ying , Liu Pian , Wang Shenming
Published: September 2021

Tamoxifen resistance remains a clinical problem in estrogen receptor (ER)-positive breast cancer. SUMOylation of ERα enhances ERα-induced transcription activity. Tripartite motif-containing (TRIM) proteins are a new class of SUMO E3 ligases, which regulate the SUMOylation of proteins. However, the precise molecular mechanism and function of TRIM3 in SUMOylation and the response to tamoxifen remain unclear. In the present study, we observed that TRIM3 was dramatically overexpressed in breast cancer, which correlated with tamoxifen resistance. Furthermore, TRIM3 overexpression significantly correlated with poor survival of patients with ER+ breast cancer treated with tamoxifen. TRIM3 overexpression conferred cell survival and tumorigenesis, whereas knocking down of TRIM3 reduced these capabilities. Moreover, TRIM3, as a ubiquitin carrier protein 9 (UBC9) binding protein, promoted SUMO modification of estrogen receptor 1 (ESR1) and activated the ER pathway. Silencing UBC9 abolished the function of TRIM3 in regulating tamoxifen resistance. These results suggest TRIM3 as a novel biomarker for breast cancer therapy, indicating that inhibiting TRIM3 combined with tamoxifen might provide a potential treatment for breast cancer.
Cellular senescence in musculoskeletal homeostasis, diseases, and regeneration
Authors: Wan Mei , Gray-Gaillard Elise F. , Elisseeff Jennifer H.
Published: September 2021

Emerging insights into cellular senescence highlight the relevance of senescence in musculoskeletal disorders, which represent the leading global cause of disability. Cellular senescence was initially described by Hayflick et al. in 1961 as an irreversible nondividing state in in vitro cell culture studies. We now know that cellular senescence can occur in vivo in response to various stressors as a heterogeneous and tissue-specific cell state with a secretome phenotype acquired after the initial growth arrest. In the past two decades, compelling evidence from preclinical models and human data show an accumulation of senescent cells in many components of the musculoskeletal system. Cellular senescence is therefore a defining feature of age-related musculoskeletal disorders, and targeted elimination of these cells has emerged recently as a promising therapeutic approach to ameliorate tissue damage and promote repair and regeneration of the skeleton and skeletal muscles. In this review, we summarize evidence of the role of senescent cells in the maintenance of bone homeostasis during childhood and their contribution to the pathogenesis of chronic musculoskeletal disorders, including osteoporosis, osteoarthritis, and sarcopenia. We highlight the diversity of the senescent cells in the microenvironment of bone, joint, and skeletal muscle tissue, as well as the mechanisms by which these senescent cells are involved in musculoskeletal diseases. In addition, we discuss how identifying and targeting senescent cells might positively affect pathologic progression and musculoskeletal system regeneration.
Predictable bonding of adhesive indirect restorations: factors for success
Authors: O´Connor Christopher , Gavriil Dimitrios
Published: September 2021

Adhesive indirect restorations are a popular restorative treatment option. This article discusses the many factors that contribute to their successful adhesive cementation, including a review of how to surface treat and manage contaminants across the wide range of indirect materials available.
A saccharide-based binder for efficient polysulfide regulations in Li-S batteries
Authors: Huang Yingyi , Shaibani Mahdokht , Gamot Tanesh D. , Wang Mingchao , Jovanović Petar , Dilusha Cooray M. C. , Mirshekarloo Meysam Sharifzadeh , Mulder Roger J. , Medhekar Nikhil V. , Hill Matthew R. , Majumder Mainak
Published: September 2021

The viability of lithium-sulfur batteries as an energy storage technology depends on unlocking long-term cycle stability. Most instability stems from the release and transport of polysulfides from the cathode, which causes mossy growth on the lithium anode, leading to continuous consumption of electrolyte. Therefore, development of a durable cathode with minimal polysulfide escape is critical. Here, we present a saccharide-based binder system that has a capacity for the regulation of polysulfides due to its reducing properties. Furthermore, the binder promotes the formation of viscoelastic filaments during casting which endows the sulfur cathode with a desirable web-like microstructure. Taken together this leads to 97% sulfur utilisation with a cycle life of 1000 cycles (9 months) and capacity retention (around 700 mAh g−1after 1000 cycles). A pouch cell prototype with a specific energy of up to 206 Wh kg−1is produced, demonstrating the promising potential for practical applications.
The RAD51 recombinase protects mitotic chromatin in human cells
Authors: Wassing Isabel E. , Graham Emily , Saayman Xanita , Rampazzo Lucia , Ralf Christine , Bassett Andrew , Esashi Fumiko
Published: September 2021

The RAD51 recombinase plays critical roles in safeguarding genome integrity, which is fundamentally important for all living cells. While interphase functions of RAD51 in maintaining genome stability are well-characterised, its role in mitosis remains contentious. In this study, we show that RAD51 protects under-replicated DNA in mitotic human cells and, in this way, promotes mitotic DNA synthesis (MiDAS) and successful chromosome segregation. In cells experiencing mild replication stress, MiDAS was detected irrespective of mitotically generated DNA damage. MiDAS broadly required de novo RAD51 recruitment to single-stranded DNA, which was supported by the phosphorylation of RAD51 by the key mitotic regulator Polo-like kinase 1. Importantly, acute inhibition of MiDAS delayed anaphase onset and induced centromere fragility, suggesting a mechanism that prevents the satisfaction of the spindle assembly checkpoint while chromosomal replication remains incomplete. This study hence identifies an unexpected function of RAD51 in promoting genomic stability in mitosis.
Mammary-specific expression of Trim24 establishes a mouse model of human metaplastic breast cancer
Authors: Shah Vrutant V. , Duncan Aundrietta D. , Jiang Shiming , Stratton Sabrina A. , Allton Kendra L. , Yam Clinton , Jain Abhinav , Krause Patrick M. , Lu Yue , Cai Shirong , Tu Yizheng , Zhou Xinhui , Zhang Xiaomei , Jiang Yan , Carroll Christopher L. , Kang Zhijun , Liu Bin , Shen Jianjun , Gagea Mihai , Manu Sebastian M. , Huo Lei , Gilcrease Michael , Powell Reid T. , Guo Lei , Stephan Clifford , Davies Peter J. , Parker-Thornburg Jan , Lozano Guillermina , Behringer Richard R. , Piwnica-Worms Helen , Chang Jeffrey T. , Moulder Stacy L. , Barton Michelle Craig
Published: September 2021

Conditional overexpression of histone readerTripartitemotif containing protein 24 (TRIM24) in mouse mammary epithelia (Trim24COE) drives spontaneous development of mammary carcinosarcoma tumors, lacking ER, PR and HER2. Human carcinosarcomas or metaplastic breast cancers (MpBC) are a rare, chemorefractory subclass of triple-negative breast cancers (TNBC). Comparison ofTrim24COEmetaplastic carcinosarcoma morphology, TRIM24 protein levels and a derivedTrim24COEgene signature reveals strong correlation with human MpBC tumors and MpBC patient-derived xenograft (PDX) models. Global and single-cell tumor profiling revealMetas a direct oncogenic target of TRIM24, leading to aberrant PI3K/mTOR activation. Here, we find that pharmacological inhibition of these pathways in primaryTrim24COEtumor cells and TRIM24-PROTAC treatment of MpBC TNBC PDX tumorspheres decreased cellular viability, suggesting potential in therapeutically targeting TRIM24 and its regulated pathways in TRIM24-expressing TNBC.
Twenty-year trends in antimicrobial resistance from aquaculture and fisheries in Asia
Authors: Schar Daniel , Zhao Cheng , Wang Yu , Larsson D. G. Joakim , Gilbert Marius , Van Boeckel Thomas P.
Published: September 2021

Antimicrobial resistance (AMR) is a growing threat to human and animal health. However, in aquatic animals—the fastest growing food animal sector globally—AMR trends are seldom documented, particularly in Asia, which contributes two-thirds of global food fish production. Here, we present a systematic review and meta-analysis of 749 point prevalence surveys reporting antibiotic-resistant bacteria from aquatic food animals in Asia, extracted from 343 articles published in 2000–2019. We find concerning levels of resistance to medically important antimicrobials in foodborne pathogens. In aquaculture, the percentage of antimicrobial compounds per survey with resistance exceeding 50% (P50) plateaued at 33% [95% confidence interval (CI) 28 to 37%] between 2000 and 2018. In fisheries, P50 decreased from 52% [95% CI 39 to 65%] to 22% [95% CI 14 to 30%]. We map AMR at 10-kilometer resolution, finding resistance hotspots along Asia’s major river systems and coastal waters of China and India. Regions benefitting most from future surveillance efforts are eastern China and India. Scaling up surveillance to strengthen epidemiological evidence on AMR and inform aquaculture and fisheries interventions is needed to mitigate the impact of AMR globally.
A randomized controlled trial of pharmacist-led therapeutic carbohydrate and energy restriction in type 2 diabetes
Authors: Durrer Cody , McKelvey Sean , Singer Joel , Batterham Alan M. , Johnson James D. , Gudmundson Kelsey , Wortman Jay , Little Jonathan P.
Published: September 2021

Type 2 diabetes can be treated, and sometimes reversed, with dietary interventions; however, strategies to implement these interventions while addressing medication changes are lacking. We conducted a 12-week pragmatic, community-based parallel-group randomized controlled trial (ClinicalTrials.gov: NCT03181165) evaluating the effect of a low-carbohydrate (<50 g), energy-restricted diet (~850-1100 kcal/day; Pharm-TCR; n = 98) compared to treatment-as-usual (TAU; n = 90), delivered by community pharmacists, on glucose-lowering medication use, cardiometabolic health, and health-related quality of life. The Pharm-TCR intervention was effective in reducing the need for glucose-lowering medications through complete discontinuation of medications (35.7%; n = 35 vs. 0%; n = 0 in TAU; p < 0.0001) and reduced medication effect score compared to TAU. These reductions occurred concurrently with clinically meaningful improvements in hemoglobin A1C, anthropometrics, blood pressure, and triglycerides (all p < 0.0001). These data indicate community pharmacists are a viable and innovative option for implementing short-term nutritional interventions for people with type 2 diabetes, particularly when medication management is a safety concern.
Geometric and biomechanical modeling aided by machine learning improves the prediction of growth and rupture of small abdominal aortic aneurysms
Authors: Lindquist Liljeqvist Moritz , Bogdanovic Marko , Siika Antti , Gasser T. Christian , Hultgren Rebecka , Roy Joy
Published: September 2021

It remains difficult to predict when which patients with abdominal aortic aneurysm (AAA) will require surgery. The aim was to study the accuracy of geometric and biomechanical analysis of small AAAs to predict reaching the threshold for surgery, diameter growth rate and rupture or symptomatic aneurysm. 189 patients with AAAs of diameters 40–50 mm were included, 161 had undergone two CTAs. Geometric and biomechanical variables were used in prediction modelling. Classifications were evaluated with area under receiver operating characteristic curve (AUC) and regressions with correlation between observed and predicted growth rates. Compared with the baseline clinical diameter, geometric-biomechanical analysis improved prediction of reaching surgical threshold within four years (AUC 0.80 vs 0.85, p = 0.031) and prediction of diameter growth rate (r = 0.17 vs r = 0.38, p = 0.0031), mainly due to the addition of semiautomatic diameter measurements. There was a trend towards increased precision of volume growth rate prediction (r = 0.37 vs r = 0.45, p = 0.081). Lumen diameter and biomechanical indices were the only variables that could predict future rupture or symptomatic AAA (AUCs 0.65–0.67). Enhanced precision of diameter measurements improves the prediction of reaching the surgical threshold and diameter growth rate, while lumen diameter and biomechanical analysis predicts rupture or symptomatic AAA.
Numerical model of the spatio-temporal dynamics in a water strider group
Authors: Kovalev Alexander , Filippov Alexander E. , Gorb Stanislav N.
Published: September 2021

The water strider group demonstrates a very complex dynamics consisting of competition for the food items, territoriality and aggression to the conspecific individuals, escaping from the predators, etc. The situation is even more complex due to the presence of different instars, which in most water strider species live in the same habitat and occupy the same niche. The presented swarm model of water striders demonstrates the realistic population dynamics. For the swarm formation in the model, attraction and repulsion forces were used. Animal motion in the model takes into account inertia and kinetic energy dissipation effects. The model includes three different rates related to the growth of individuals: food appearance rate, food assimilation rate, and stored energy loss rate. The results of our modeling show that the size distribution of individuals seems to be an adequate measure for population status, and it has a characteristic shape for different model parameter combinations. Distribution of the distances between nearest neighbors is other important measure of the population density and its dynamics. Parameters of the model can be tuned in such a way, that the shape of both distributions in a steady phase coincides with that shape observed in a natural population, which helps to understand the factors leading to particular momentary distribution of both parameters (size and distance) in the population. From this point of view, the model can predict how both distributions can further develop from certain state depending on particular combination of factors.
Linear analysis of Atwood number effects on shear instability in the elastic–plastic solids
Authors: Wang Xi , Hu Xiao-Mian , Wang Sheng-Tao , Pan Hao , Yin Jian-Wei
Published: September 2021

The evolution of shear instability between elastic–plastic solid and ideal fluid which is concerned in oblique impact is studied by developing an approximate linear theoretical model. With the velocities expressed by the velocity potentials from the incompressible and irrotational continuity equations and the pressures obtained by integrating momentum equations with arbitrary densities, the motion equations of the interface amplitude are deduced by considering the continuity of normal velocities and the force equilibrium with the perfectly elastic–plastic properties of solid at interface. The completely analytical formulas of the growth rate and the amplitude evolution are achieved by solving the motion equations. Consistent results are performed by the model and 2D Lagrange simulations. The characteristics of the amplitude development and Atwood number effects on the growth are discussed. The growth of the amplitude is suppressed by elastic–plastic properties of solids in purely elastic stage or after elastic–plastic transition, and the amplitude oscillates if the interface is stable. The system varies from stable to unstable state as Atwood number decreasing. For large Atwood number, elastic–plastic properties play a dominant role on the interface evolution which may influence the formation of the wavy morphology of the interface while metallic plates are suffering obliquely impact.
Self-care tooling innovation in a disabled kea (Nestor notabilis)
Authors: Bastos Amalia P. M. , Horváth Kata , Webb Jonathan L. , Wood Patrick M. , Taylor Alex H.
Published: September 2021

Tooling is associated with complex cognitive abilities, occurring most regularly in large-brained mammals and birds. Among birds, self-care tooling is seemingly rare in the wild, despite several anecdotal reports of this behaviour in captive parrots. Here, we show that Bruce, a disabled parrot lacking his top mandible, deliberately uses pebbles to preen himself. Evidence for this behaviour comes from five lines of evidence: (i) in over 90% of instances where Bruce picked up a pebble, he then used it to preen; (ii) in 95% of instances where Bruce dropped a pebble, he retrieved this pebble, or replaced it, in order to resume preening; (iii) Bruce selected pebbles of a specific size for preening rather than randomly sampling available pebbles in his environment; (iv) no other kea in his environment used pebbles for preening; and (v) when other individuals did interact with stones, they used stones of different sizes to those Bruce preened with. Our study provides novel and empirical evidence for deliberate self-care tooling in a bird species where tooling is not a species-specific behaviour. It also supports claims that tooling can be innovated based on ecological necessity by species with sufficiently domain-general cognition.
Temperature dependence of the microwave dielectric properties of $$\gamma$$-aminobutyric acid
Authors: Hou Jie , Abie Sisay Mebre , Strand-Amundsen Runar , Galperin Yuri M. , Bergli Joakim , Schuelke Christin , Hashemizadeh Sina , Martinsen Ørjan Grøttem
Published: September 2021

The GABA molecule is the major inhibitory neurotransmitter in the mammalian central nervous system. Through binding to post-synaptic neurons, GABA reduces the neuronal excitability by hyperpolarization. Correct binding between the GABA molecules and its receptors relies on molecular recognition. Earlier studies suggest that recognition is determined by the geometries of the molecule and its receptor. We employed dielectric relaxation spectroscopy (DRS) to study the conformation and dielectric properties of the GABA molecule under physiologically relevant laboratory conditions. The dielectric properties of GABA investigated have given us new insights about the GABA molecule, such as how they interact with each other and with water molecules at different temperatures (22°C and 37.5°C). Higher temperature leads to lower viscosity, thus lower relaxation time. The change in the GABA relaxation time due to concentration change is more associated with the solution viscosity than with the GABA dipole moment. A resonance behavior was observed with high GABA concentrations at physiological temperature, where there might be a phase transition at a certain temperature for a given GABA concentration that leads to a sudden change of the dielectric properties.
Phosphopantetheinyl transferase binding and inhibition by amidino-urea and hydroxypyrimidinethione compounds
Authors: Carivenc Coralie , Maveyraud Laurent , Blanger Claire , Ballereau Stéphanie , Roy-Camille Coralie , Nguyen Minh Chau , Génisson Yves , Guilhot Christophe , Chalut Christian , Pedelacq Jean-Denis , Mourey Lionel
Published: September 2021

Owing to their role in activating enzymes essential for bacterial viability and pathogenicity, phosphopantetheinyl transferases represent novel and attractive drug targets. In this work, we examined the inhibitory effect of the aminido-urea 8918 compound against the phosphopantetheinyl transferases PptAb fromMycobacterium abscessusand PcpS fromPseudomonas aeruginosa,two pathogenic bacteria associated with cystic fibrosis and bronchiectasis, respectively. Compound 8918 exhibits inhibitory activity against PptAb but displays no activity against PcpS in vitro, while no antimicrobial activity againstMycobacterium abscessusorPseudomonas aeruginosacould be detected. X-ray crystallographic analysis of 8918 bound to PptAb-CoA alone and in complex with an acyl carrier protein domain in addition to the crystal structure of PcpS in complex with CoA revealed the structural basis for the inhibition mechanism of PptAb by 8918 and its ineffectiveness against PcpS. Finally,in crystalloscreening of potent inhibitors from the National Cancer Institute library identified a hydroxypyrimidinethione derivative that binds PptAb. Both compounds could serve as scaffolds for the future development of phosphopantetheinyl transferases inhibitors.