bluuebunny/crossref_metadata_2025 huggingface dataset:
Approach to Stereotactic Body Radiotherapy for the Treatment of Advanced Hepatocellular Carcinoma in Patients with Child-Pugh B-7 Cirrhosis
Authors: Daniell Kayla M. , Banson Kara Micah , Diamond Brett H. , Sioshansi Shirin
Published: November 2022

Opinion statement

Patients with hepatocellular carcinoma (HCC) with underlying Child-Pugh B-7 cirrhosis benefit from management from an experienced, multidisciplinary team. In patients with localized disease who meet criteria for liver transplant, establishing care at a liver transplant center is crucial. For those awaiting transplant, local bridge therapies have emerged as a strategy to maintain priority status and eligibility. Multiple liver-directed therapies exist to provide locoregional tumor control. The careful selection of locoregional therapy is a multidisciplinary endeavor that takes into account patient factors including tumor resectability, underlying liver function, performance status, previous treatment, tumor location/size, and vascular anatomy to determine the optimal management strategy. Technological advances in external beam radiation therapy have allowed stereotactic body radiation therapy (SBRT) to emerge in recent years as a versatile and highly effective bridge therapy consisting of typically between 3 and 5 high dose, highly focused, and non-invasive radiation treatments. When treating cirrhotic patients with HCC, preserving liver function is of utmost importance to prevent clinical decline and decompensation. SBRT has been shown to be both safe and effective in carefully selected patients with Child-Pugh B cirrhosis; however, care must be taken to prevent radiation-induced liver disease. This review summarizes the evolving role of SBRT in the treatment of HCC in patients with Child-Pugh B-7 cirrhosis.
Crosstalk between ROCK1 and PYROXD1 regulates CAFs activation and promotes laryngeal squamous cell carcinoma metastasis
Authors: Yang Liyun , Qiao Peipei , Zhang Jianwei , Chen Xiaoping , Hu An , Huang Shuixian
Published: November 2022

We previously found that the Rho-associated kinase 1 (ROCK1) activated Cancer-associated fibroblasts (CAFs) to promote LSCC metastasis. Accumulating evidence indicates that pyridine nucleotide-disulfide oxidoreductase domain 1 (PYROXD1) is an oncogene; however, the crosstalk between ROCK1 and PYROXD1 in LSCC metastasis remains largely unknown. Here, we found that ROCK1 could target PYROXD1. The knockdown of ROCK1 expression reduces the expression of PYROXD1, while the knockdown of PYROXD1 expression did not alter the expression of ROCK1 indicating that ROCK1 is upstream of PYROXD1. Further, LSCC cells cocultured with PYROXD1 knocked-down CAFs exhibited lower proliferation, migration, invasion and metastasis abilities. Conversely, LSCC cells cocultured with PYROXD1-overexpressing CAFs showed opposite results. In conclusion, the crosstalk between ROCK1 and PYROXD1 regulated CAFs activation and promoted LSCC metastasis.
Rigorous numerical inclusion of the blow-up time for the Fujita-type equation
Authors: Mizuguchi Makoto , Sekine Kouta , Hashimoto Kouji , Nakao Mitsuhiro T. , Oishi Shin’ichi
Published: November 2022

Multiple studies have addressed the blow-up time of the Fujita-type equation. However, an explicit and sharp inclusion method that tackles this problem is still missing due to several challenging issues. In this paper, we propose a method for obtaining a computable and mathematically rigorous inclusion of the $$L^2(\varOmega )$$

L
2

(
Ω
)

blow-up time of a solution to the Fujita-type equation subject to initial and Dirichlet boundary conditions using a numerical verification method. More specifically, we develop a computer-assisted method, by using the numerically verified solution for nonlinear parabolic equations and its estimation of the energy functional, which proves that the concerned solution blows up in the $$L^2(\varOmega )$$

L
2

(
Ω
)

sense in finite time with a rigorous estimation of this time. To illustrate how our method actually works, we consider the Fujita-type equation with Dirichlet boundary conditions and the initial function $$u(0,x)=\frac{192}{5}x(x-1)(x^2-x-1)$$

u

(
0
,
x
)

=

192
5

x

(
x
-
1
)

(

x
2

-
x
-
1
)

in a one-dimensional domain $$\varOmega$$
Ω
and demonstrate its efficiency in predicting $$L^2(\varOmega )$$

L
2

(
Ω
)

blow-up time. The existing theory cannot prove that the solution of the equation blows up in $$L^2(\varOmega )$$

L
2

(
Ω
)

. However, our proposed method shows that the solution is the $$L^2(\varOmega )$$

L
2

(
Ω
)

blow-up solution and the $$L^2(\varOmega )$$

L
2

(
Ω
)

blow-up time is in the interval (0.3068, 0.317713].
The role of identity in digital consumer behavior: A conceptual model and research propositions based on gender
Authors: Rogova Natalia , Matta Shashi
Published: November 2022

Nowadays consumers can express their identities not only through their possessions and buying behavior, but also using social media and digital networks. This article aims to understand these digital consumer behaviors by focusing on identity strength and the identity signaling phenomenon. We develop a conceptual model that combines internal and external factors to explain the intensity and content of digital identity-related behaviors. We use the example of gender identity to build our research propositions, as gender is one of the most frequently and intensely debated identities in online consumer discussions. Further, we propose how digital and offline identity signaling behaviors are intertwined, and discuss the online behaviors of trans consumers. In doing so, our conceptual work highlights the unique features of digital identity signaling behaviors as well as the complexity of identities, including gender, and provides useful insights for researchers and marketers.
Influence of Resistance Training Proximity-to-Failure on Skeletal Muscle Hypertrophy: A Systematic Review with Meta-analysis
Authors: Refalo Martin C. , Helms Eric R. , Trexler Eric. T. , Hamilton D. Lee , Fyfe Jackson J.
Published: November 2022

Background and Objective

This systematic review with meta-analysis investigated the influence of resistance training proximity-to-failure on muscle hypertrophy.

Methods

Literature searches in the PubMed, SCOPUS and SPORTDiscus databases identified a total of 15 studies that measured muscle hypertrophy (in healthy adults of any age and resistance training experience) and compared resistance training performed to: (A) momentary muscular failure versus non-failure; (B) set failure (defined as anything other than momentary muscular failure) versus non-failure; or (C) different velocity loss thresholds.

Results

There was a trivial advantage for resistance training performed to set failure versus non-failure for muscle hypertrophy in studies applying any definition of set failure [effect size=0.19 (95% confidence interval 0.00, 0.37), p=0.045], with no moderating effect of volume load (p=0.884) or relative load (p=0.525). Given the variability in set failure definitions applied across studies, sub-group analyses were conducted and found no advantage for either resistance training performed to momentary muscular failure versus non-failure for muscle hypertrophy [effect size=0.12 (95% confidence interval −0.13, 0.37), p=0.343], or for resistance training performed to high (>25%) versus moderate (20–25%) velocity loss thresholds [effect size=0.08 (95% confidence interval −0.16, 0.32), p=0.529].

Conclusion

Overall, our main findings suggest that (i) there is no evidence to support that resistance training performed to momentary muscular failure is superior to non-failure resistance training for muscle hypertrophy and (ii) higher velocity loss thresholds, and theoretically closer proximities-to-failure do not always elicit greater muscle hypertrophy. As such, these results provide evidence for a potential non-linear relationship between proximity-to-failure and muscle hypertrophy.
A new approach to construct 3-D crustal shear-wave velocity models: method description and application to the Central Alps
Authors: Colavitti Leonardo , Hetényi György ,   the AlpArray Working Group
Published: November 2022

We develop a new inversion approach to construct a 3-D structural and shear-wave velocity model of the crust based on teleseismic P-to-S converted waves. The proposed approach does not require local earthquakes such as body wave tomography, nor a large aperture seismic network such as ambient noise tomography, but a three-component station network with spacing similar to the expected crustal thickness. The main features of the new method are: (1) a novel model parametrization with 3-D mesh nodes that are fixed in the horizontal directions but can flexibly vary vertically; (2) the implementation of both sharp velocity changes across discontinuities and smooth gradients; (3) an accurate ray propagator that respects Snell’s law in 3-D at any interface geometry. Model parameters are inverted using a stochastic method composed of simulated annealing followed by a pattern search algorithm. The first application is carried out over the Central Alps, where long-standing permanent and the temporary AlpArray Seismic Network stations provide an ideal coverage. For this study we invert 4 independent parameters, which are the Moho discontinuity depth, the Conrad discontinuity depth, the P-velocity change at the Conrad and the average Vp/Vs of the crust. The 3-D inversion results clearly image the roots of the Alpine orogen, including the Ivrea Geophysical Body. The lower crust's thickness appears fairly constant. Average crustal Vp/Vs ratios are relatively higher beneath the orogen, and a low-Vp/Vs area in the northern foreland seems to correlate with lower crustal earthquakes, which can be related to mechanical differences in rock properties, probably inherited. Our results are in agreement with those found by 3-D ambient noise tomography, though our method inherently performs better at localizing discontinuities. Future developments of this technique can incorporate joint inversions, as well as more efficient parameter space exploration.
Attuali applicazioni della determinazione dei livelli plasmatici di copeptina in contesti non-endocrinologici
Authors: Berton Alessandro Maria , Varaldo Emanuele , Prencipe Nunzia , Rumbolo Francesca , Settanni Fabio , Benso Andrea , Grottoli Silvia
Published: November 2022

Sommario

Copeptina (CT-proAVP) rappresenta l’affidabile marker di secrezione dell’arginin-vasopressina (AVP) e nella pratica clinica endocrinologica viene impiegata per la diagnosi differenziale della sindrome poliurica-polidipsica. Negli ultimi anni, tuttavia, sono state indagate applicazioni alternative di tale glicopeptide in setting differenti. In questa rassegna sono esaminate, in particolare, le sue più interessanti proposte di utilizzo in ambito cardiovascolare, infettivologico e nefrologico.
Development of a Hybrid Adaptive Neuro-fuzzy Inference System with Coulomb-Counting State-of-Charge Estimator for Lithium–Sulphur Battery
Authors: Valencia Nicolas , Fotouhi Abbas , Shateri Neda , Auger Daniel
Published: November 2022

This study presents the development of an improved state of charge (SOC) estimation technique for lithium–sulphur (Li–S) batteries. This is a promising technology with advantages in comparison with the existing lithium-ion (Li-ion) batteries such as lower production cost and higher energy density. In this study, a state-of-the-art Li–S prototype cell is subjected to experimental tests, which are carried out to replicate real-life duty cycles. A system identification technique is then used on the experimental test results to parameterize an equivalent circuit model for the Li–S cell. The identification results demonstrate unique features of the cell’s voltage-SOC and ohmic resistance-SOC curves, in which a large flat region is observed in the middle SOC range. Due to this, voltage and resistance parameters are not sufficient to accurately estimate SOC under various initial conditions. To solve this problem, a forgetting factor recursive least squares (FFRLS) identification technique is used, yielding four parameters which are then used to train an adaptive neuro-fuzzy inference system (ANFIS). The Sugeno-type fuzzy system features four inputs and one output (SOC), totalling 375 rules. Each of the inputs features Gaussian-type membership functions while the output is of a linear type. This network is then combined with the coulomb-counting method to obtain a hybrid estimator that can accurately estimate SOC for a Li–S cell under various conditions with a maximum error of 1.64%, which outperforms the existing methods of Li–S battery SOC estimation.
Oxygen Functionalization-Induced Charging Effect on Boron Active Sites for High-Yield Electrocatalytic NH3 Production
Authors: Biswas Ashmita , Kapse Samadhan , Thapa Ranjit , Dey Ramendra Sundar
Published: November 2022

Ammonia has been recognized as the future renewable energy fuel because of its wide-ranging applications in H2 storage and transportation sector. In order to avoid the environmentally hazardous Haber–Bosch process, recently, the third-generation ambient ammonia synthesis has drawn phenomenal attention and thus tremendous efforts are devoted to developing efficient electrocatalysts that would circumvent the bottlenecks of the electrochemical nitrogen reduction reaction (NRR) like competitive hydrogen evolution reaction, poor selectivity of N2 on catalyst surface. Herein, we report the synthesis of an oxygen-functionalized boron carbonitride matrix via a two-step pyrolysis technique. The conductive BNCO(1000) architecture, the compatibility of B-2pz orbital with the N-2pz orbital and the charging effect over B due to the C and O edge-atoms in a pentagon altogether facilitate N2 adsorption on the B edge-active sites. The optimum electrolyte acidity with 0.1 M HCl and the lowered anion crowding effect aid the protonation steps of NRR via an associative alternating pathway, which gives a sufficiently high yield of ammonia (211.5 μg h−1 mgcat−1) on the optimized BNCO(1000) catalyst with a Faradaic efficiency of 34.7% at − 0.1 V vs RHE. This work thus offers a cost-effective electrode material and provides a contemporary idea about reinforcing the charging effect over the secured active sites for NRR by selectively choosing the electrolyte anions and functionalizing the active edges of the BNCO(1000) catalyst.
Cross disciplinary teaching: A pedagogical model to support teachers in the development and implementation of outdoor learning opportunities
Authors: Neville Ian A. , Petrass Lauren A. , Ben Francis
Published: November 2022

There is a growing body of empirical evidence documenting the positive effects associated with participation in environmental education and outdoor learning for students, teachers and the wider community. Despite this, there has been a substantial reduction in outdoor learning opportunities for school students, possibly due to the focus on evidenced-based outcomes, high-stakes standardised testing programs, and a lack of teacher knowledge, confidence and expertise in teaching and learning outdoors. Accordingly, this study presents an evidenced based model to support teaching practice. The model will assist teachers in the development and implementation of outdoor learning opportunities and offers applied examples that address curriculum outcomes. A comprehensive literature review methodology was implemented to identify peer-reviewed literature on teaching and learning outdoors and outdoor pedagogies. A thematic synthesis and constant comparative technique enabled development of themes, from which three themes emerged: the environment; the learner; and the educator, which inform the proposed model offered by the authors. The three interrelated components (the environment, the learner and the educator) require consideration for students to gain maximum benefit from outdoor learning experiences. The model, coupled with the applied examples, supports teachers to plan and facilitate immersive outdoor experiences that promote learning.
The effects of selenium supplementation on inflammatory markers in critically ill patients
Authors: Mahmoodpoor Ata , Faramarzi Elnaz , Reyhanifard Anita , Shamekh Ali , Nikanfar Saba , Azizi-Zeinalhajlou Akbar , Sanaie Sarvin
Published: November 2022

Low serum selenium (Se) levels have been shown in critical illness, which is associated with poor clinical outcomes and a higher mortality rate. Se plays an important role in inflammation and oxidative stress. Since the overproduction of inflammatory cytokines and increased oxidative stress is a major component of critical illnesses, its supplementation has been demonstrated to have promising effects on critically ill patients. This study aims to review the evidence regarding the effects of Se supplementation on inflammatory and oxidative markers in critically ill patients. The literature review highlights alterations of inflammatory markers, including procalcitonin, leukocyte count, albumin, prealbumin, C-reactive protein (CRP), inflammatory cytokines, and cholesterol following Se supplementation in critically ill patients. Besides, the antioxidant properties of Se due to its presence in the structure of several selenoenzymes have been reported.

Article highlights

Low serum Se level have been shown in critical illness, which is associated with poor clinical outcome and higher mortality rate.

Se plays an important role in inflammation and oxidative stress.

Se supplementation can have promising effects by alterations of inflammatory markers and its antioxidant properties for critically ill patients.
Frequentist Conditional Variance for Nonlinear Mixed-Effects Models
Authors: Zheng Nan , Cadigan Noel
Published: November 2022

Nonlinear mixed-effects models are commonly used in fisheries and ecological studies to account for complex relationships and dependencies in data. These models involve both fixed parameters to estimate and random-effects (REs) to predict. This paper addresses the inferential setting involving repeated sampling of the data but conditional on the unknown REs. This setting is more appropriate when the focus is on statistical inferences based on the specific values of REs that generated the data. Assuming the Laplace approximation is appropriate to derive the marginal likelihood and following a frequentist framework, this work derives RE-conditional bias approximations of maximum likelihood parameter estimators and empirical Bayes RE predictors, as well as the conditional covariance and mean squared error (MSE) among parameter estimators and RE predictors. It is shown that the RE-conditional MSE can be approximated with the unconditional MSE. Simulation studies demonstrate that the variance and MSE approximations are reasonably accurate for relevant sample sizes. Considering the finite-sample RE-conditional biases in the parameter estimates and RE predictions, the MSE is more appropriate for constructing confidence intervals (CIs), and the CI coverage of REs should be interpreted as the average coverage over a range of REs or over repeated generation of REs.
In Vitro Collagenase Degradation of Grafts Used Clinically for Anterior Cruciate Ligament Reconstruction: Human Tendon Data
Authors: Ventura Ben , Ashton Dylan M. , Clarke Elizabeth C. , Hartnell Nicholas , Haubruck Patrick , Hefferan Samantha A. , Little Christopher B. , Blaker Carina L.
Published: November 2022

Increasing anterior cruciate ligament (ACL) rupture rates are driving the need for new graft materials which undergo testing to characterize material properties and function. The in vitro collagenase assay is routinely used to determine the degradation rate of collagenous materials. At times, it is used to screen new biomaterials on the basis that results reflect breakdown rates in vivo. However, its predictive potential is inconclusive with no guidelines for acceptable in vitro rates of degradation. Reference data from target tissue/s or existing clinical materials are needed to determine appropriate thresholds. From a summary of reported protocols, the most common bench conditions (bacterial collagenase; unloaded samples) were used to evaluate the in vitro degradation of human tendons used as ACL allografts: patellar, semitendinosus, gracilis, Achilles, tibialis anterior and posterior. Tendons were sectioned in equal volumes and exposed to 100 U collagenase for 1, 2, 4 or 8 h. The change in dry weight was analysed using mixed linear regression. All tendon samples demonstrated a significant reduction in mass over time but the patellar tendon degraded significantly faster than all other tendons (P ≤ 0.004). As all tendons used in this study are clinically accepted, this study provides a range of human tendon reference data for comparative assessment of new tendon and ligament biomaterials. However, the more rapid degradation of the patellar tendon, one of the most successful ACL graft materials, also highlights the limitations of common collagenase assay conditions for predicting in vivo performance, particularly in the absence of suitable comparative controls.
Effects of ICTs on the Terms of Trade of Sub-Saharan African Economies
Authors: Nzepang Fabrice , Nguenda Anya Saturnin Bertrand
Published: November 2022

This paper argues that the increasing adoption of information and communication technologies (ICTs) is a factor that improves the terms of trade of sub-Saharan African (SSA) economies. According to new theories of international trade, ICTs can change the terms of trade by increasing productivity, reducing costs, and increasing human capital endowment and specialization. Here, we use World Development Indicators (WDI) and United Nations Conference on Trade and Development (UNCTAD) data over the period from 2005 to 2017 and a vector autoregression (VAR) model on a panel of 39 SSA countries to illustrate the importance of ICTs in this regard. Our results show that the change in the terms-of-trade index is positively affected by the change in the number of internet users as a percentage of mobile phone subscribers in SSA. Furthermore, an impulse response function shows that a shock that would increase the number of internet users by 10 percent of mobile phone subscribers would result in the terms-of-trade index gains of more than 5% within about a year.
Electron Scattering for Nuclear and Nucleon Structure
Authors: Walecka John Dirk
Published: November 2022

The scattering of high-energy electrons from nuclear and nucleon targets provides a microscope for examining the structure of these tiny objects. The best evidence we have on what nuclei and nucleons actually look like comes from electron scattering. This 2001 book examines the motivation for electron scattering and develops the theoretical analysis of the process. It discusses our theoretical understanding of the underlying structure of nuclei and nucleons at appropriate levels of resolution and sophistication, and summarizes experimental electron scattering capabilities. Only a working knowledge of quantum mechanics and special relativity is assumed, making this a suitable textbook for graduate and advanced undergraduate courses. It will also provide a valuable summary and reference for researchers already working in electron scattering and other areas of nuclear and particle physics. This text has been reissued as an Open Access publication on Cambridge Core.
Salt consumption and mortality risk in cirrhotic patients: results from a cohort study
Authors: Pashayee-Khamene Fereshteh , Hajimohammadebrahim-Ketabforoush Melika , Saber-Firoozi Mahdi , Hatami Behzad , Naseri Kaveh , Karimi Sara , Ahmadzadeh Saleheh , Kord Hamed , Saadati Saeede , Hekmatdoost Azita
Published: November 2022

Since conducting a long-term randomised clinical trial is not logical and feasible to find the optimum dosage of salt intake in patients with cirrhosis, cohort studies are the best design to assess the long-term effects of dietary salt on the survival of cirrhotic patients. This cohort study aimed to evaluate the association between dietary intake of salt and mortality risk in cirrhotic patients. The present study was designed as a cohort in three referral hospitals in Iran in 2018. One hundred and twenty-one patients aged between 20 and 70 years with established cirrhosis were recruited. Dietary intakes, demographic data and disease severity were evaluated at the baseline. Participants were followed up annually. Crude survival was greater in patients with low-to-moderate salt consumption rather than in those with high consumption, and in non-consumers [34⋅26 (95 % CI 33⋅04, 35⋅49) v. 30⋅41 (95 % CI 27⋅13, 33⋅69) v. 32⋅72 (95 % CI 30⋅63, 34⋅80), P = 0⋅028; log-rank test]. Using the Cox proportional hazard model, it was shown that the risk of mortality in the high-salt consumption category was approximately 126 % higher than that of the reference category (non-consumers) [HR value 2⋅26, (95 % CI 0⋅91, 5⋅63)], while this risk for the low-to-moderate consumption group was about 28 % lower than the reference category [HR value 0⋅72, (95 % CI 0⋅26, 1⋅99), P-trend = 0⋅04]. In conclusion, a high daily dietary intake of salt might increase the rate of mortality and moderate salt restriction (instead of elimination of salt) decreases the risk of death.
MCADAM: A Continuous Paleomagnetic Dipole Moment Model for at Least 3.7 Billion Years
Authors: Bono Richard K. , Paterson Greig A. , Biggin Andrew J.
Published: November 2022

Understanding the evolution of Earth's magnetic field can provide insights into core processes and can constrain plate tectonics and atmospheric shielding. The absolute paleointensity database PINT provides a curated repository of site mean (i.e., cooling unit), estimates of the strength of the magnetic field. We present a minor update to the PINT database to version 8.1.1 by adding 295 records from 34 studies. The PINT database is used to define a continuous model of the dipole field, using an approach combining non‐parametric and Monte Carlo (MC) resampling termed Monte Carlo Axial Dipole Average Model (MCADAM). Three dipole field strength models spanning 50 ka to 3.7–4.2 Ga (MCADAM.1a‐c) are presented, reflecting three tiers of increasingly more stringent data selection. The MCADAM models allow for the estimation of the magnetic standoff distance, constraining the shielding of Earth's atmosphere against solar wind erosion provided by the geodynamo.
Evaluating cognitive disturbances as treatment target and predictor of antidepressant action in major depressive disorder: A NeuroPharm study
Authors: Dam Vibeke Høyrup , Stenbæk Dea Siggaard , Köhler-Forsberg Kristin , Cheng Ip  , Ozenne Brice , Sahakian Barbara Jacquelyn , Knudsen Gitte Moos , Jørgensen Martin Balslev , Frokjaer Vibe Gedsoe
Published: November 2022

Cognitive disturbances in major depressive disorder (MDD) constitute a critical treatment target and hold promise as an early predictor of antidepressant treatment response; yet their clinical relevance is not fully established. Therefore, we here investigate if (1) cognitive performance improves over the course of antidepressant treatment and (2) cognitive performance at baseline is predictive of antidepressant treatment response. In the NeuroPharm study (clinical trial id: NCT02869035), 92 antidepressant-free patients with a moderate to severe depressive episode were assessed with a comprehensive cognitive test battery including both cold (emotion-independent) and hot (emotion-dependent) tasks. Patients were tested before and after 12 weeks of standard antidepressant treatment with escitalopram in flexible doses of 10–20 mg. Performance improved across most cognitive domains over the course of antidepressant treatment. Notably, these improvements were independent of improvement in mood symptoms, emphasizing that cognitive disturbances are a distinct symptom and therefore treatment target in MDD. Results did not suggest that performance on any single cognitive measure at baseline was associated with later clinical response to antidepressant treatment. However, a small cluster of patients (N = 28) with globally disturbed cognition at baseline exhibited poorer clinical response after 8 but not 12 weeks of antidepressant treatment, suggesting that severe cognitive disturbances may delay treatment response. Thus, while pretreatment cognitive performance on individual tests may not be useful as clinical markers of treatment response, profiles capturing performance across different cognitive domains may be useful for stratification of patients with MDD and could be helpful in future intervention trials.
Ferroptosis: a double-edged sword mediating immune tolerance of cancer
Authors: Dang Qin , Sun Ziqi , Wang Yang , Wang Libo , Liu Zaoqu , Han Xinwei
Published: November 2022

The term ferroptosis was put forward in 2012 and has been researched exponentially over the past few years. Ferroptosis is an unconventional pattern of iron-dependent programmed cell death, which belongs to a type of necrosis and is distinguished from apoptosis and autophagy. Actuated by iron-dependent phospholipid peroxidation, ferroptosis is modulated by various cellular metabolic and signaling pathways, including amino acid, lipid, iron, and mitochondrial metabolism. Notably, ferroptosis is associated with numerous diseases and plays a double-edged sword role. Particularly, metastasis-prone or highly-mutated tumor cells are sensitive to ferroptosis. Hence, inducing or prohibiting ferroptosis in tumor cells has vastly promising potential in treating drug-resistant cancers. Immunotolerant cancer cells are not sensitive to the traditional cell death pathway such as apoptosis and necroptosis, while ferroptosis plays a crucial role in mediating tumor and immune cells to antagonize immune tolerance, which has broad prospects in the clinical setting. Herein, we summarized the mechanisms and delineated the regulatory network of ferroptosis, emphasized its dual role in mediating immune tolerance, proposed its significant clinical benefits in the tumor immune microenvironment, and ultimately presented some provocative doubts. This review aims to provide practical guidelines and research directions for the clinical practice of ferroptosis in treating immune-resistant tumors.
Associations of hurricane exposure and forecasting with impaired birth outcomes
Authors: Hochard Jacob , Li Yuanhao , Abashidze Nino
Published: November 2022

Early forecasts give people in a storm’s path time to prepare. Less is known about the cost to society when forecasts are incorrect. In this observational study, we examine over 700,000 births in the path of Hurricane Irene and find exposure was associated with impaired birth outcomes. Additional warning time was associated with decreased preterm birth rates for women who experienced intense storm exposures documenting a benefit of avoiding a type II forecasting error. A larger share of this at-risk population experienced a type I forecasting error where severe physical storm impacts were anticipated but not experienced. Disaster anticipation disrupted healthcare services by delaying and canceling prenatal care, which may contribute to storm-impacted birth outcomes. Recognizing storm damages depend on human responses to predicted storm paths is critical to supporting the next generation’s developmental potential with judicious forecasts that ensure public warning systems mitigate rather than exacerbate climate damages.
Learning the histone codes with large genomic windows and three-dimensional chromatin interactions using transformer
Authors: Lee Dohoon , Yang Jeewon , Kim Sun
Published: November 2022

The quantitative characterization of the transcriptional control by histone modifications has been challenged by many computational studies, but most of them only focus on narrow and linear genomic regions around promoters, leaving a room for improvement. We present Chromoformer, a transformer-based, three-dimensional chromatin conformation-aware deep learning architecture that achieves the state-of-the-art performance in the quantitative deciphering of the histone codes in gene regulation. The core essence of Chromoformer architecture lies in the three variants of attention operation, each specialized to model individual hierarchy of transcriptional regulation involving from core promoters to distal elements in contact with promoters through three-dimensional chromatin interactions. In-depth interpretation of Chromoformer reveals that it adaptively utilizes the long-range dependencies between histone modifications associated with transcription initiation and elongation. We also show that the quantitative kinetics of transcription factories and Polycomb group bodies can be captured by Chromoformer. Together, our study highlights the great advantage of attention-based deep modeling of complex interactions in epigenomes.
Active boundary layers in confined active nematics
Authors: Hardoüin Jerôme , Doré Claire , Laurent Justine , Lopez-Leon Teresa , Ignés-Mullol Jordi , Sagués Francesc
Published: November 2022

The role of boundary layers in conventional liquid crystals is commonly related to the mesogen anchoring on confining walls. In the classical view, anchoring enslaves the orientational field of the passive material under equilibrium conditions. In this work, we show that an active nematic can develop active boundary layers that topologically polarize the confining walls. We find that negatively-charged defects accumulate in the boundary layer, regardless of the wall curvature, and they influence the overall dynamics of the system to the point of fully controlling the behavior of the active nematic in situations of strong confinement. Further, we show that wall defects exhibit behaviors that are essentially different from those of their bulk counterparts, such as high motility or the ability to recombine with another defect of like-sign topological charge. These exotic behaviors result from a change of symmetry induced by the wall in the director field around the defect. Finally, we suggest that the collective dynamics of wall defects might be described in terms of a model equation for one-dimensional spatio-temporal chaos.
Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR
Authors: Sempou Emily , Kostiuk Valentyna , Zhu Jie , Cecilia Guerra M. , Tyan Leonid , Hwang Woong , Camacho-Aguilar Elena , Caplan Michael J. , Zenisek David , Warmflash Aryeh , Owens Nick D. L. , Khokha Mustafa K.
Published: November 2022

Transitioning from pluripotency to differentiated cell fates is fundamental to both embryonic development and adult tissue homeostasis. Improving our understanding of this transition would facilitate our ability to manipulate pluripotent cells into tissues for therapeutic use. Here, we show that membrane voltage (Vm) regulates the exit from pluripotency and the onset of germ layer differentiation in the embryo, a process that affects both gastrulation and left-right patterning. By examining candidate genes of congenital heart disease and heterotaxy, we identifyKCNH6, a member of the ether-a-go-go class of potassium channels that hyperpolarizes the Vmand thus limits the activation of voltage gated calcium channels, lowering intracellular calcium. In pluripotent embryonic cells, depletion ofkcnh6leads to membrane depolarization, elevation of intracellular calcium levels, and the maintenance of a pluripotent state at the expense of differentiation into ectodermal and myogenic lineages. Using high-resolution temporal transcriptome analysis, we identify the gene regulatory networks downstream of membrane depolarization and calcium signaling and discover that inhibition of the mTOR pathway transitions the pluripotent cell to a differentiated fate. By manipulating Vmusing a suite of tools, we establish a bioelectric pathway that regulates pluripotency in vertebrates, including human embryonic stem cells.
Ion rectification based on gel polymer electrolyte ionic diode
Authors: Jiang Fan , Poh Wei Church , Chen Juntong , Gao Dace , Jiang Feng , Guo Xiaoyu , Chen Jian , Lee Pooi See
Published: November 2022

Biological ion channels rely on ions as charge carriers and unidirectional ion flow to produce and transmit signals. To realize artificial biological inspired circuitry and seamless human-machine communication, ion-transport-based rectification devices should be developed. In this research, poly(methyl methacrylate) (PMMA) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) gel polymer electrolytes (GPEs) are assembled to construct a novel ionic diode, enabling ion rectification through ion-diffusion/migration that emulates biological systems. This ion rectification results from the different diffusion/migration behaviors of mobile ions transporting in the GPE heterojunction. The electrical tests of the GPE heterojunction reveal outstanding rectifying ratio of 23.11. The GPE ionic diode operates in wide temperature window, from −20 °C (anti-freezing) to 125 °C (thermal tolerance). The absence of redox reactions is verified in the cyclic voltammogram. The GPE ionic diodes are used to construct ionic logic gates for signal communication. Furthermore, rectification of a triboelectric nanogenerator and potential for synaptic devices are demonstrated.
Systematic tissue annotations of genomics samples by modeling unstructured metadata
Authors: Hawkins Nathaniel T. , Maldaver Marc , Yannakopoulos Anna , Guare Lindsay A. , Krishnan Arjun
Published: November 2022

There are currently >1.3 million human –omics samples that are publicly available. This valuable resource remains acutely underused because discovering particular samples from this ever-growing data collection remains a significant challenge. The major impediment is that sample attributes are routinely described using varied terminologies written in unstructured natural language. We propose a natural-language-processing-based machine learning approach (NLP-ML) to infer tissue and cell-type annotations for genomics samples based only on their free-text metadata. NLP-ML works by creating numerical representations of sample descriptions and using these representations as features in a supervised learning classifier that predicts tissue/cell-type terms. Our approach significantly outperforms an advanced graph-based reasoning annotation method (MetaSRA) and a baseline exact string matching method (TAGGER). Model similarities between related tissues demonstrate that NLP-ML models capture biologically-meaningful signals in text. Additionally, these models correctly classify tissue-associated biological processes and diseases based on their text descriptions alone. NLP-ML models are nearly as accurate as models based on gene-expression profiles in predicting sample tissue annotations but have the distinct capability to classify samples irrespective of the genomics experiment type based on their text metadata. Python NLP-ML prediction code and trained tissue models are available athttps://github.com/krishnanlab/txt2onto.
Hippocampal convergence during anticipatory midbrain activation promotes subsequent memory formation
Authors: Poh Jia-Hou , Vu Mai-Anh T. , Stanek Jessica K. , Hsiung Abigail , Egner Tobias , Adcock R. Alison
Published: November 2022

The hippocampus has been a focus of memory research since H.M’s surgery abolished his ability to form new memories, yet its mechanistic role in memory remains debated. Here, we identify a candidate memory mechanism: an anticipatory hippocampal “convergence state”, observed while awaiting valuable information, and which predicts subsequent learning. During fMRI, participants viewed trivia questions eliciting high or low curiosity, followed seconds later by its answer. We reasoned that encoding success requires a confluence of conditions, so that hippocampal states more conducive to memory formation should converge in state space. To operationalize convergence of neural states, we quantified the typicality of multivoxel patterns in the medial temporal lobes during anticipation and encoding of trivia answers. We found that the typicality of anticipatory hippocampal patterns increased during high curiosity. Crucially, anticipatory hippocampal pattern typicality increased with dopaminergic midbrain activation and uniquely accounted for the association between midbrain activation and subsequent recall. We propose that hippocampal convergence states may complete a cascade from motivation and midbrain activation to memory enhancement, and may be a general predictor of memory formation.
GZMKhigh CD8+ T effector memory cells are associated with CD15high neutrophil abundance in non-metastatic colorectal tumors and predict poor clinical outcome
Authors: Tiberti Silvia , Catozzi Carlotta , Croci Ottavio , Ballerini Mattia , Cagnina Danilo , Soriani Chiara , Scirgolea Caterina , Gong Zheng , He Jiatai , Macandog Angeli D. , Nabinejad Amir , Nava Lauson Carina B. , Quinte’ Arianna , Bertalot Giovanni , Petz Wanda L. , Ravenda Simona P. , Licursi Valerio , Paci Paola , Rasponi Marco , Rotta Luca , Fazio Nicola , Ren Guangwen , Fumagalli-Romario Uberto , Schaefer Martin H. , Campaner Stefano , Lugli Enrico , Nezi Luigi , Manzo Teresa
Published: November 2022

CD8+T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune cells impacts on clinical outcome is still in its infancy. Here, we describe that the interaction of tumor infiltrating neutrophils expressing high levels of CD15 with CD8+T effector memory cells (TEM) correlates with tumor progression. Mechanistically, stromal cell-derived factor-1 (CXCL12/SDF-1) promotes the retention of neutrophils within tumors, increasing the crosstalk with CD8+T cells. As a consequence of the contact-mediated interaction with neutrophils, CD8+T cells are skewed to produce high levels of GZMK, which in turn decreases E-cadherin on the intestinal epithelium and favors tumor progression. Overall, our results highlight the emergence of GZMKhighCD8+TEMin non-metastatic CRC tumors as a hallmark driven by the interaction with neutrophils, which could implement current patient stratification and be targeted by novel therapeutics.
Economic interests cloud hazard reductions in the European regulation of substances of very high concern
Authors: Coria Jessica , Kristiansson Erik , Gustavsson Mikael
Published: November 2022

Here we investigate how the conflicts between hazard reduction and economic interests have shaped the regulation of substances of very high concern (SVHCs) under the Authorization program of the European chemical regulation Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH). Since regulation starts with listing SVHCs on the Candidate List, we analyze the relative importance of toxicological properties, economic motivations, and available scientific knowledge on the probability of inclusion on the Candidate List. We find that the most important factor in whether a substance is listed is whether it is being produced in, or imported into, the European Economic Area (EEA), with the regulators less likely to place a substance on the list if it is currently being produced or imported in the EEA. This evidence suggests that regulators have listed chemicals of secondary importance leading to lesser than anticipated hazard reductions, either because production and imports had already ceased before the listing, or because the compound has never been produced or imported in the EEA at all.
Peptide-enhanced tough, resilient and adhesive eutectogels for highly reliable strain/pressure sensing under extreme conditions
Authors: Zhang Yan , Wang Yafei , Guan Ying , Zhang Yongjun
Published: November 2022

Natural gels and biomimetic hydrogel materials have been able to achieve outstanding integrated mechanical properties due to the gain of natural biological structures. However, nearly every natural biological structure relies on water as solvents or carriers, which limits the possibility in extreme conditions, such as sub-zero temperatures and long-term application. Here, peptide-enhanced eutectic gels were synthesized by introducing α-helical “molecular spring” structure into deep eutectic solvent. The gel takes full advantage of the α-helical structure, achieving high tensile/compression, good resilience, superior fracture toughness, excellent fatigue resistance and strong adhesion, while it also inherits the benefits of the deep eutectic solvent and solves the problems of solvent volatilization and freezing. This enables unprecedentedly long and stable sensing of human motion or mechanical movement. The electrical signal shows almost no drift even after 10,000 deformations for 29 hours or in the −20 °C to 80 °C temperature range.
Analysis of matched primary and recurrent BRCA1/2 mutation-associated tumors identifies recurrence-specific drivers
Authors: Shah Jennifer B. , Pueschl Dana , Wubbenhorst Bradley , Fan Mengyao , Pluta John , D’Andrea Kurt , Hubert Anna P. , Shilan Jake S. , Zhou Wenting , Kraya Adam A. , Llop Guevara Alba , Ruan Catherine , Serra Violeta , Balmaña Judith , Feldman Michael , Morin Pat J. , Nayak Anupma , Maxwell Kara N. , Domchek Susan M. , Nathanson Katherine L.
Published: November 2022

Recurrence is a major cause of death amongBRCA1/2mutation carriers with breast (BrCa) and ovarian cancers (OvCa). Herein we perform multi-omic sequencing on 67 paired primary and recurrent BrCa and OvCa from 27BRCA1/2mutation carriers to identify potential recurrence-specific drivers.PARP1amplifications are identified in recurrences (False Discovery Rate q = 0.05), andPARP1is significantly overexpressed across primary BrCa and recurrent BrCa and OvCa, independent of amplification status. RNA sequencing analysis finds twoBRCA2isoforms,BRCA2-201/LongandBRCA2-001/Short, respectively predicted to be sensitive and insensitive to nonsense-mediated decay.BRCA2-001/Shortis expressed more frequently in recurrences and associated with reduced overall survival in breast cancer (87 vs. 121 months; Hazard Ratio = 2.5 [1.18–5.5]). Loss of heterozygosity (LOH) status is discordant in 25% of patient’s primary and recurrent tumors, with switching between both LOH and lack of LOH found. Our study reveals multiple potential drivers of recurrent disease inBRCA1/2mutation-associated cancer, improving our understanding of tumor evolution and suggesting potential biomarkers.
Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice
Authors: Gul Seref , Akyel Yasemin Kubra , Gul Zeynep Melis , Isin Safak , Ozcan Onur , Korkmaz Tuba , Selvi Saba , Danis Ibrahim , Ipek Ozgecan Savlug , Aygenli Fatih , Taskin Ali Cihan , Akarlar Büşra Aytül , Ozlu Nurhan , Ozturk Nuri , Ozturk Narin , Ünal Durişehvar Özer , Guzel Mustafa , Turkay Metin , Okyar Alper , Kavakli Ibrahim Halil
Published: November 2022

Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis. Here, we discovered a molecule (M47) that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The M47 selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and resulted in increasing the circadian period length of U2OSBmal1-dLuccells. In addition, subcellular fractionation studies from mice liver indicated that M47 increased degradation of the CRY1 in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced oxaliplatin-induced apoptosis in Ras-transformedp53null fibroblast cells. Systemic repetitive administration of M47 increased the median lifespan ofp53−/−mice by ~25%. Collectively our data suggest that M47 is a promising molecule to treat forms of cancer depending on thep53mutation.