bluuebunny/crossref_metadata_2025_split huggingface dataset:
The transcription factor OsWRKY10 inhibits phosphate uptake via suppressingOsPHT1;2expression under phosphate-replete conditions in rice
Authors: Wang Shichao , Xu Tingting , Chen Min , Geng Liyan , Huang Zhaoyang , Dai Xiaoli , Qu Hongye , Zhang Jun , Li Huanhuan , Gu Mian , Xu Guohua 
Published: November 2022

AbstractPlants have evolved delicate systems for stimulating or inhibiting inorganic phosphate (Pi) uptake in response to the fluctuating Pi availability in soil. However, the negative regulators inhibiting Pi uptake at the transcriptional level are largely unexplored. Here, we functionally characterized a transcription factor in rice (Oryza sativa), OsWRKY10. OsWRKY10 encodes a nucleus-localized protein and showed preferential tissue localization. Knockout of OsWRKY10 led to increased Pi uptake and accumulation under Pi-replete conditions. In accordance with this phenotype, OsWRKY10 was transcriptionally induced by Pi, and a subset of PHOSPHATE TRANSPORTER 1 (PHT1) genes were up-regulated upon its mutation, suggesting that OsWRKY10 is a transcriptional repressor of Pi uptake. Moreover, rice plants expressing the OsWRKY10–VP16 fusion protein (a dominant transcriptional activator) accumulated even more Pi than oswrky10. Several lines of biochemical evidence demonstrated that OsWRKY10 directly suppressed OsPHT1;2 expression. Genetic analysis showed that OsPHT1;2 was responsible for the increased Pi accumulation in oswrky10. Furthermore, during Pi starvation, OsWRKY10 protein was degraded through the 26S proteasome. Altogether, the OsWRKY10–OsPHT1;2 module represents a crucial loop in the Pi signaling network in rice, inhibiting Pi uptake when there is ample Pi in the environment.
Rubisco, the imperfect winner: it’s all about the base
Authors: Badger Murray R , Sharwood Robert E 
Published: November 2022

Abstract
Rubisco catalysis is complex and includes an activation step through the formation of a carbamate at the conserved active site lysine residue and the formation of a highly reactive enediol that is the key to its catalytic reaction. The formation of this enediol is both the basis of its success and its Achilles’ heel, creating imperfections to its catalytic efficiency. While Rubisco originally evolved in an atmosphere of high CO2, the earth’s multiple oxidation events provided challenges to Rubisco through the fixation of O2 that competes with CO2 at the active site. Numerous catalytic screens across the Rubisco superfamily have identified significant variation in catalytic properties that have been linked to large and small subunit sequences. Despite this, we still have a rudimentary understanding of Rubisco’s catalytic mechanism and how the evolution of kinetic properties has occurred. This review identifies the lysine base that functions both as an activator and a proton abstractor to create the enediol as a key to understanding how Rubisco may optimize its kinetic properties. The ways in which Rubisco and its partners have overcome catalytic and activation imperfections and thrived in a world of high O2, low CO2, and variable climatic regimes is remarkable.
Investigating the shift between externally and internally oriented cognition: a novel task-switching paradigm
Authors: Calzolari Sara , Boneva Svetla , Fernández-Espejo Davinia 
Published: November 2022

Abstract
Despite our constant need to flexibly balance internal and external information, research on cognitive flexibility has focused solely on shifts between externally oriented tasks. In contrast, switches across internally oriented processes (and self-referential cognition specifically) and between internal and external domains have never been investigated. Here, we report a novel task-switching paradigm developed to explore the behavioural signatures associated with cognitive flexibility when self-referential processes, as well as more traditional external processes, are involved. Two hundred healthy volunteers completed an online task. In each trial, participants performed one of four possible tasks on written words, as instructed by a pre-stimulus cue. These included two externally and two internally oriented tasks: assessing whether the third letter was a consonant or the penultimate letter was a vowel versus assessing whether the adjective applied to their personality or if it described a bodily sensation they were currently experiencing. In total, 40% of trials involved switches to another task, and these were equally distributed across within-external, within-internal, internal-to-external and external-to-internal switches. We found higher response times for switches compared to repetitions both in the external and internal domains, thus demonstrating the presence of switch costs in self-referential tasks for the first time. We also found higher response times for between-domain switches compared to switches within each domain. We propose that these effects originate from the goal-directed engagement of different domain-specific cognitive systems that flexibly communicate and share domain-general control features.
Phase I study of a novel glioblastoma radiation therapy schedule exploiting cell-state plasticity
Authors: Dean Jamie A , Tanguturi Shyam K , Cagney Daniel , Shin Kee-Young , Youssef Gilbert , Aizer Ayal , Rahman Rifaquat , Hammoudeh Lubna , Reardon David , Lee Eudocia , Dietrich Jorg , Tamura Kaoru , Aoyagi Masaru , Wickersham Lacey , Wen Patrick Y , Catalano Paul , Haas-Kogan Daphne , Alexander Brian M , Michor Franziska 
Published: November 2022

Abstract

Background
Glioblastomas comprise heterogeneous cell populations with dynamic, bidirectional plasticity between treatment-resistant stem-like and treatment-sensitive differentiated states, with treatment influencing this process. However, current treatment protocols do not account for this plasticity. Previously, we generated a mathematical model based on preclinical experiments to describe this process and optimize a radiation therapy fractionation schedule that substantially increased survival relative to standard fractionation in a murine glioblastoma model.

Methods
We developed statistical models to predict the survival benefit of interventions to glioblastoma patients based on the corresponding survival benefit in the mouse model used in our preclinical study. We applied our mathematical model of glioblastoma radiation response to optimize a radiation therapy fractionation schedule for patients undergoing re-irradiation for glioblastoma and developed a first-in-human trial (NCT03557372) to assess the feasibility and safety of administering our schedule.

Results
Our statistical modeling predicted that the hazard ratio when comparing our novel radiation schedule with a standard schedule would be 0.74. Our mathematical modeling suggested that a practical, near-optimal schedule for re-irradiation of recurrent glioblastoma patients was 3.96 Gy × 7 (1 fraction/day) followed by 1.0 Gy × 9 (3 fractions/day). Our optimized schedule was successfully administered to 14/14 (100%) patients.

Conclusions
A novel radiation therapy schedule based on mathematical modeling of cell-state plasticity is feasible and safe to administer to glioblastoma patients.
Upfront BRAF/MEK inhibitors for treatment of high-grade glioma: A case report and review of the literature
Authors: Arbour Gabrielle , Ellezam Benjamin , Weil Alexander G , Cayrol Romain , Vanan Magimairajan Issai , Coltin Hallie , Larouche Valérie , Erker Craig , Jabado Nada , Perreault Sébastien 
Published: November 2022

Abstract

Background
High-grade gliomas (HGG) with BRAFV600E mutation represent a unique subset of central nervous system tumors. Targeted therapies including BRAF and MEK inhibitors are now being explored as possible new treatment options.

Methods
We report an 18-year-old female with a grade 3 pleomorphic xanthoastrocytoma treated upfront with dabrafenib and trametinib. We also conducted a systematic literature review of patients with HGG and BRAFV600E mutations treated with BRAF inhibitors.

Results
Despite local recurrences resected surgically, the patient has been on dabrafenib and trametinib for more than 54 months. Thirty-two patients with HGG and BRAFV600E mutations treated with BRAF inhibitors were retrieved through our systematic review of the literature. Only 1 young patient with an anaplastic ganglioglioma was treated upfront with a BRAF inhibitor with a curative intent. Best response reported with radiation therapy and systemic therapy was a stable disease (SD) for 18 patients (56.3%) and progressive disease (PD) for 9 patients (28.1%). Responses to treatment regimens that included BRAF inhibitors were reported in 31 patients and included 4 complete responses (12.9%), 23 partial responses (74.2%), 2 SDs (6.5%), and 2 PDs (6.5%).

Conclusions
Our patient had durable disease control with dabrafenib and trametinib. Given favorable responses reported in patients with HGG treated with BRAF inhibitors, we believe that upfront targeted therapy is a possible treatment approach that should be studied in the context of a clinical trial.
Strong Neutralizing Antibody Responses to SARS-CoV-2 Variants Following a Single Vaccine Dose in Subjects With Previous SARS-CoV-2 Infection
Authors: Ekström Nina , Haveri Anu , Solastie Anna , Virta Camilla , Österlund Pamela , Nohynek Hanna , Nieminen Tuomo , Ivaska Lauri , Tähtinen Paula A , Lempainen Johanna , Jalkanen Pinja , Julkunen Ilkka , Palmu Arto A , Melin Merit 
Published: November 2022

Abstract

Background
Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primes the immune system; thus individuals who have recovered from infection have enhanced immune responses to subsequent vaccination (hybrid immunity). However, it remains unclear how well hybrid immunity induced by severe or mild infection can cross-neutralize emerging variants. We aimed to compare the strength and breadth of antibody responses in vaccinated recovered and uninfected subjects.

Methods
We measured spike-specific immunoglobulin (Ig)G and neutralizing antibodies (NAbs) from vaccinated subjects including 320 with hybrid immunity and 20 without previous infection. From 29 subjects with a previous severe or mild infection, we also measured NAb responses against Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529/BA.1) variants following vaccination.

Results
A single vaccine dose induced 2-fold higher anti-spike IgG concentrations and up to 4-fold higher neutralizing potency of antibodies in subjects with a previous infection compared with vaccinated subjects without a previous infection. Hybrid immunity was more enhanced after a severe than a mild infection, with sequentially decreasing NAb titers against Alpha, Beta, Delta, and Omicron variants. We found similar IgG concentrations in subjects with a previous infection after 1 or 2 vaccine doses.

Conclusions
Hybrid immunity induced strong IgG responses, particularly after severe infection. However, the NAb titers were low against heterologous variants, especially against Omicron.
Determinants of Antiretroviral Treatment Success and Adherence in People With Human Immunodeficiency Virus Treated for Tuberculosis
Authors: De Castro Nathalie , Chazallon Corine , N'takpe Jean-Baptiste , Timana Isabel , Escada Rodrigo , Wagner Sandra , Messou Eugène , Eholie Serge , Bhatt Nilesh , Khosa Celso , Laureillard Didier , Do Chau Giang , Veloso Valdilea G , Delaugerre Constance , Anglaret Xavier , Molina Jean-Michel , Grinsztejn Beatriz , Marcy Olivier ,   for the ANRS 12300 Reflate TB2 Study Group
Published: November 2022

Abstract

Background
In people with human immunodeficiency virus [HIV] presenting with advanced disease, rates of virologic success may be lower than expected. The Reflate TB2 trial did not show non-inferiority of raltegravir versus efavirenz in people with HIV (PWH) treated for tuberculosis. We aimed to identify factors associated with virologic success and higher adherence in the trial.

Methods
In this analysis, we included participants enrolled in the Reflate TB2 trial with adherence data available. The primary outcome was virologic success (HIV-1 ribonucleic acid [RNA] &lt;50 copies/mL) at week 48, and the secondary outcome was adherence as assessed by the pill count adherence ratio. We used logistic regression to study determinants of virologic success and optimal adherence in 2 separate analyses.

Results
Four hundred forty-four participants were included in the present analysis. Over the 48-week follow-up period, 290 of 444 (65%) participants had a pill count adherence ratio ≥95%. At week 48, 288 of 444 (65%) participants were in virologic success. In the multivariate analysis, female sex (adjusted odds ratio [aOR], 1.77; 95% confidence interval [CI], 1.16–2.72; P = .0084), lower baseline HIV-1 RNA levels (&lt;100 000; aOR, 2.29; 95% CI, 1.33–3.96; P = .0087), and pill count adherence ratio ≥95% (aOR, 2.38; 95% CI, 1.56–3.62; P &lt; .0001) were independently associated with virologic success. Antiretroviral pill burden was the only factor associated with pill count adherence ratio ≥95% (OR, 0.81; 95% CI, .71–.92; P = .0018).

Conclusions
In PWH with tuberculosis receiving raltegravir or efavirenz-based regimens, female sex, optimal adherence, and baseline HIV-1 RNA &lt;100 000 copies/mL were associated with virologic success, and the number of antiretroviral tablets taken daily was a strong predictor of adherence.
Pro-Inflammatory Alterations of Circulating Monocytes in Latent Tuberculosis Infection
Authors: Feria Manuel G , Chang Cecilia , Ticona Eduardo , Moussa Anissa , Zhang Bin , Ballena Isabel , Azañero Ruben , Ticona Cesar , De Cecco Carlo N , Fichtenbaum Carl J , O’Donnell Robert E , La Rosa Alberto , Sanchez Jorge , Andorf Sandra , Atehortua Laura , Katz Jonathan D , Chougnet Claire A , Deepe George S , Huaman Moises A 
Published: November 2022

AbstractBackgroundLatent tuberculosis infection (LTBI) has been associated with increased cardiovascular risk. We investigated the activation and pro-inflammatory profile of monocytes in individuals with LTBI and their association with coronary artery disease (CAD).MethodsIndividuals 40–70 years old in Lima, Peru, underwent QuantiFERON-TB testing to define LTBI, completed a coronary computed tomography angiography to evaluate CAD, and provided blood for monocyte profiling using flow cytometry. Cells were stimulated with lipopolysaccharide to assess interleukin-6 (IL-6) and tumor necrosis factor (TNF)–α responses.ResultsThe clinical characteristics of the LTBI (n = 28) and non-LTBI (n = 41) groups were similar. All monocyte subsets from LTBI individuals exhibited higher mean fluorescence intensity (MFI) of CX3CR1 and CD36 compared with non-LTBI individuals. LTBI individuals had an increased proportion of nonclassical monocytes expressing IL-6 (44.9 vs 26.9; P = .014), TNF-α (62.3 vs 35.1; P = .014), and TNF-α+IL-6+ (43.2 vs 36.6; P = .042). Among LTBI individuals, CAD was associated with lower CX3CR1 MFI on classical monocytes and lower CD36 MFI across all monocyte subsets. In multivariable analyses, lower CD36 MFI on total monocytes (b = −0.17; P = .002) and all subsets remained independently associated with CAD in LTBI.ConclusionsIndividuals with LTBI have distinct monocyte alterations suggestive of an exacerbated inflammatory response and tissue migration. Whether these alterations contribute to cardiovascular disease pathogenesis warrants further investigation.
Knowing behavior matters doesn’t hurt: the effect of individual climate behavior messaging on green policy support
Authors: Rakhimov Abdurakhim , Thulin Erik 
Published: November 2022

Abstract
Individual behavior change offers a large potential to curb greenhouse gas emissions. However, messaging promoting individual behavior change has been criticized as a strategy for addressing climate change due to its potential to diminish climate policy support. In a pre-registered study with a representative sample of American adults (n = 1069), we found that messages recommending the adoption of high-impact individual climate behaviors, such as flying less, eating less meat and reducing food waste, and highlighting their large impact do not affect support for a carbon tax. In an exploratory analysis, we found that this messaging results in a higher intention to adopt several climate behaviors. We recommend that interventions that advocate for individual climate action be best understood as complements, rather than undermining substitutes, to broad carbon regulatory policy.
Confirmation bias and vaccine-related beliefs in the time of COVID-19
Authors: Malthouse Eugene 
Published: November 2022

Abstract

Background
In recent history mass vaccination has proved essential to dealing with pandemics. However, the effectiveness of a vaccine depends on the number of people willing to take it. One approach to encouraging uptake is to publish information about safety and effectiveness. But confirmation bias research in other domains suggests that people may evaluate this information through the lens of their existing beliefs.

Methods
This study used a simple 2 × 2 design to investigate whether people’s (n = 3899) existing beliefs influenced their ability to correctly evaluate data from a fictional trial presented in a frequency table. Treatment groups saw different trial outcomes (intervention effective versus ineffective and trial related versus unrelated to vaccines).

Results
Results provided robust evidence for confirmation bias in the domain of vaccines: people made systematic errors (P &lt; 0.01) when evaluating evidence that was inconsistent with their prior beliefs. This pattern emerged among people with both pro-vaccination and anti-vaccination attitudes. Errors were attributed to confirmation bias because no such differences were detected when participants evaluated data unrelated to vaccines.

Conclusions
People are prone to misinterpreting evidence about vaccines in ways that reflect their underlying beliefs. Confirmation bias is an important consideration for vaccine communication.
NLP-based tools for localization of the Epileptogenic Zone in patients with drug-resistant focal epilepsy
Authors: Mora Sara , Turrisi Rosanna , Chiarella Lorenzo , Tassi Laura , Mai Roberto , Nobili Lino , Barla Annalisa , Arnulfo Gabriele 
Published: November 2022

AbstractBackgroundDrug-resistant focal epilepsy, defined by failure of two antiepileptic drugs, affects about 30% of patients with epilepsy. Epilepsy surgery may represent an alternative options for this population. However, defining the epileptogenic zone to be surgically removed requires highly specialised medical expertise as well as advanced technologies. The aim of this work is building a cost-effective support system based on text, in particular based on the semiological descriptions of the seizures (temporal vs extratemporal lobe; right vs left hemisphere), in order to predict the localization of seizure origin.MethodsAmong a population of 121 surgically treated and seizure-free drug-resistant patients suffering with focal epilepsy, recruited at the Niguarda Hospital in Milan, we extracted a total number of 509 descriptions of seizures. After a data pre-processing phase, we used natural language processing tools to build numerical representations of the seizures descriptions, both using embedding and countbased methods. We then used machine learning models performing a binary classification into right/left and temporal/extra-temporal.ResultsAll predictive models show a better performance when using the representations relying on embedding models respect to count-based ones. Between all the combinations of representations and classifiers, the best performance obtained in terms of F1-score is 84.7%±0.6.DiscussionThis preliminary work reached encouraging results considering both localization tasks. The main advantage is that no specific knowledge about epilepsy is used to build the models, rendering our pipeline applicable also in other scenarios. The major limitation lies in the fact that the text is highly specific to the writer.
Accurate Computational Design of 3D Protein Crystals
Authors: Li Zhe , Wang Shunzhi , Nattermann Una , Bera Asim K. , Borst Andrew J. , Bick Matthew J. , Yang Erin C. , Sheffler William , Lee Byeongdu , Seifert Soenke , Nguyen Hannah , Kang Alex , Dalal Radhika , Lubner Joshua M. , Hsia Yang , Haddox Hugh , Courbet Alexis , Dowling Quinton , Miranda Marcos , Favor Andrew , Etemadi Ali , Edman Natasha I. , Yang Wei , Sankaran Banumathi , Negahdari Babak , Baker David 
Published: November 2022

SummaryProtein crystallization plays a central role in structural biology1, with broad impact2in pharmaceutical formulation3, drug delivery4, biosensing5, and biocatalysis6,7. Despite this importance, the process of protein crystallization remains poorly understood and highly empirical8–10, with largely unpredictable crystal contacts, lattice packing arrangements, and space group preferences, and the programming of protein crystallization through precisely engineered sidechain-sidechain interactions across multiple protein-protein interfaces is an outstanding challenge. Here we develop a general computational approach to designing three-dimensional (3D) protein crystals with pre-specified lattice architectures at atomic accuracy that hierarchically constrains the overall degree of freedoms (DOFs) of the system. We use the approach to design three pairs of oligomers that can be individually purified, and upon mixing, spontaneously self-assemble into large 3D crystals (>100 μm). Small-angle X-ray scattering and X-ray crystallography show these crystals are nearly identical to the computational design models, with the design targetF4132 andI432 space groups and closely corresponding overall architectures and protein-protein interfaces. The crystal unit cell dimensions can be systematically redesigned while retaining space group symmetry and overall architecture, and the crystals are both extremely porous and highly stable, enabling the robust scaffolding of inorganic nanoparticle arrays. Our approach thus enables the computational design of protein crystals with high accuracy, and since both structure and assembly are encoded in the primary sequence, provides a powerful new platform for biological material engineering.
Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state
Authors: Barrett Thomas F. , Patel Bhuvic , Khan Saad M. , Yim Aldrin K.Y. , Pugazenthi Sangami , Mahlokozera Tatenda , Mullins Riley D.Z. , Zipfel Gregory J. , Herzog Jacques A. , Chicoine Michael R. , Wick Cameron C. , Durakovic Nedim , Osbun Joshua W. , Shew Matthew , Sweeney Alex D. , Patel Akash J. , Buchman Craig A. , Petti Allegra A. , Puram Sidharth V. , Kim Albert H. 
Published: November 2022

ABSTRACTVestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to the pathogenesis of these tumors remains poorly understood. We performed scRNA-seq on 15 VS samples, with paired scATAC-seq in six samples. We identified diverse Schwann cell (SC), stromal, and immune populations in the VS TME and found that repair-like and MHC-II antigen presenting subtype SCs are associated with increased myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors revealed Injury-like tumors are associated with larger tumor size, and scATAC-seq identified transcription factors associated with nerve repair among SCs from Injury-like tumors. Ligand-receptor analysis and functionalin vitroexperiments suggested that SCs recruit monocytes. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be targeted to prevent tumor progression.