bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogeny-linked occurrence of ribosome stalling on the mRNAs of Arabidopsis unfolded protein response factor bZIP60 orthologs in divergent plant species
Authors: Imamichi Tomoya , Kusumoto Nao , Aoyama Haruka , Takamatsu Seidai , Honda Yugo , Muraoka Shiori , Hagiwara-Komoda Yuka , Chiba Yukako , Onouchi Hitoshi , Yamashita Yui , Naito Satoshi 
Published: February 2024

Abstract
The bZIP60, XBP1 and HAC1 mRNAs encode transcription factors that mediate the unfolded protein response (UPR) in plants, animals and yeasts, respectively. Upon UPR, these mRNAs undergo unconventional cytoplasmic splicing on the endoplasmic reticulum (ER) to produce active transcription factors. Although cytoplasmic splicing is conserved, the ER targeting mechanism differs between XBP1 and HAC1. The ER targeting of HAC1 mRNA occurs before translation, whereas that of XBP1 mRNA involves a ribosome-nascent chain complex that is stalled when a hydrophobic peptide emerges from the ribosome; the corresponding mechanism is unknown for bZIP60. Here, we analyzed ribosome stalling on bZIP60 orthologs of plants. Using a cell-free translation system, we detected nascent peptide-mediated ribosome stalling during the translation elongation of the mRNAs of Arabidopsis, rice and Physcomitrium (moss) orthologs, and the termination-step stalling in the Selaginella (lycopod) ortholog, all of which occurred ∼50 amino acids downstream of a hydrophobic region. Transfection experiments showed that ribosome stalling contributes to cytoplasmic splicing in bZIP60u orthologs of Arabidopsis and Selaginella. In contrast, ribosome stalling was undetectable for liverwort, Klebsormidium (basal land plant), and green algae orthologs. This study highlights the evolutionary diversity of ribosome stalling and its contribution to ER targeting in plants.
Unfilled gaps by polβ lead to aberrant ligation by LIG1 at the downstream steps of base excision repair pathway
Authors: Gulkis Mitchell , Martinez Ernesto , Almohdar Danah , Çağlayan Melike 
Published: February 2024

Abstract
Base excision repair (BER) involves the tightly coordinated function of DNA polymerase β (polβ) and DNA ligase I (LIG1) at the downstream steps. Our previous studies emphasize that defective substrate-product channeling, from gap filling by polβ to nick sealing by LIG1, can lead to interruptions in repair pathway coordination. Yet, the molecular determinants that dictate accurate BER remains largely unknown. Here, we demonstrate that a lack of gap filling by polβ leads to faulty repair events and the formation of deleterious DNA intermediates. We dissect how ribonucleotide challenge and cancer-associated mutations could adversely impact the ability of polβ to efficiently fill the one nucleotide gap repair intermediate which subsequently results in gap ligation by LIG1, leading to the formation of single-nucleotide deletion products. Moreover, we demonstrate that LIG1 is not capable of discriminating against nick DNA containing a 3′-ribonucleotide, regardless of base-pairing potential or damage. Finally, AP-Endonuclease 1 (APE1) shows distinct substrate specificity for the exonuclease removal of 3′-mismatched bases and ribonucleotides from nick repair intermediate. Overall, our results reveal that unfilled gaps result in impaired coordination between polβ and LIG1, defining a possible type of mutagenic event at the downstream steps where APE1 could provide a proofreading role to maintain BER efficiency.
Site-specific incorporation of a fluorescent nucleobase analog enhances i-motif stability and allows monitoring of i-motif folding inside cells
Authors: Mir Bartomeu , Serrano-Chacón Israel , Medina Pedro , Macaluso Veronica , Terrazas Montserrat , Gandioso Albert , Garavís Miguel , Orozco Modesto , Escaja Núria , González Carlos 
Published: February 2024

Abstract
The i-motif is an intriguing non-canonical DNA structure, whose role in the cell is still controversial. Development of methods to study i-motif formation under physiological conditions in living cells is necessary to study its potential biological functions. The cytosine analog 1,3-diaza-2-oxophenoxazine (tCO) is a fluorescent nucleobase able to form either hemiprotonated base pairs with cytosine residues, or neutral base pairs with guanines. We show here that when tCO is incorporated in the proximity of a G:C:G:C minor groove tetrad, it induces a strong thermal and pH stabilization, resulting in i-motifs with Tm of 39ºC at neutral pH. The structural determination by NMR methods reveals that the enhanced stability is due to a large stacking interaction between the guanines of the tetrad with the tCO nucleobase, which forms a tCO:C+ in the folded structure at unusually-high pHs, leading to an increased quenching in its fluorescence at neutral conditions. This quenching is much lower when tCO is base-paired to guanines and totally disappears when the oligonucleotide is unfolded. By taking profit of this property, we have been able to monitor i-motif folding in cells.
Cryo-EM structure of SRP68/72 reveals an extended dimerization domain with RNA-binding activity
Authors: Zhong Yichen , Feng Junjie , Koh Adrian F , Kotecha Abhay , Greber Basil J , Ataide Sandro F 
Published: February 2024

Abstract
The signal recognition particle (SRP) is a critical component in protein sorting pathways in all domains of life. Human SRP contains six proteins bound to the 7S RNA and their structures and functions have been mostly elucidated. The SRP68/72 dimer is the largest SRP component and is essential for SRP function. Although the structures of the SRP68/72 RNA binding and dimerization domains have been previously reported, the structure and function of large portions of the SRP68/72 dimer remain unknown. Here, we analyse full-length SRP68/72 using cryo-EM and report that SRP68/72 depend on each other for stability and form an extended dimerization domain. This newly observed dimerization domain is both a protein- and RNA-binding domain. Comparative analysis with current structural models suggests that this dimerization domain undergoes dramatic translocation upon SRP docking onto SRP receptor and eventually comes close to the Alu domain. We propose that the SRP68/72 dimerization domain functions by binding and detaching the Alu domain and SRP9/14 from the ribosomal surface, thus releasing elongation arrest upon docking onto the ER membrane.
A European Renal Association (ERA) synopsis for nephrology practice of the 2023 European Society of Hypertension (ESH) Guidelines for the Management of Arterial Hypertension
Authors: Sarafidis Pantelis , Schmieder Roland , Burnier Michel , Persu Alexandre , Januszewicz Andrzej , Halimi Jean-Michel , Arici Mustafa , Ortiz Alberto , Wanner Christoph , Mancia Giuseppe , Kreutz Reinhold 
Published: February 2024

ABSTRACT
In June 2023, the European Society of Hypertension (ESH) presented and published the new 2023 ESH Guidelines for the Management of Arterial Hypertension, a document that was endorsed by the European Renal Association (ERA). Following the evolution of evidence in recent years, several novel recommendations relevant to the management of hypertension in patients with chronic kidney disease (CKD) appeared in these Guidelines. These include recommendations for target office blood pressure (BP) &lt;130/80 mmHg in most and against target office BP &lt;120/70 mmHg in all patients with CKD; recommendations for use of spironolactone or chlorthalidone for patients with resistant hypertension with estimated glomerular filtration rate (eGFR) higher or lower than 30 mL/min/1.73 m2, respectively; use of a sodium-glucose cotransporter 2 inhibitor for patients with CKD and estimated eGFR ≥20 mL/min/1.73 m2; use of finerenone for patients with CKD, type 2 diabetes mellitus, albuminuria, eGFR ≥25 mL/min/1.73 m2 and serum potassium &lt;5.0 mmol/L; and revascularization in patients with atherosclerotic renovascular disease and secondary hypertension or high-risk phenotypes if stenosis ≥70% is present. The present report is a synopsis of sections of the ESH Guidelines that are relevant to the daily clinical practice of nephrologists, prepared by experts from ESH and ERA. The sections summarized are those referring to the role of CKD in hypertension staging and cardiovascular risk stratification, the evaluation of hypertension-mediated kidney damage and the overall management of hypertension in patients with CKD.
Dual p38MAPK and MEK inhibition disrupts adaptive chemoresistance in mesenchymal glioblastoma to temozolomide
Authors: Cheng Hong Sheng , Chong Yuk Kien , Lim Eldeen Kai Yi , Lee Xin Yi , Pang Qing You , Novera Wisna , Marvalim Charlie , Lee Jeannie Xue Ting , Ang Beng Ti , Tang Carol , Tan Nguan Soon 
Published: February 2024

Abstract

Background
Precision treatment of glioblastoma is increasingly focused on molecular subtyping, with the mesenchymal subtype particularly resistant to temozolomide. Here, we aim to develop a targeted therapy for temozolomide resensitization in the mesenchymal subtype.

Methods
We integrated kinomic profiles and kinase inhibitor screens from patient-derived proneural and mesenchymal glioma-propagating cells and public clinical datasets to identify key protein kinases implicated in temozolomide resistance. RNAseq, apoptosis assays, and comet assays were used to examine the role of p38MAPK signaling and adaptive chemoresistance in mesenchymal cells. The efficacy of dual p38MAPK and MEK/ERK inhibition using ralimetinib (selective orally active p38MAPK inhibitor; phase I/II for glioblastoma) and binimetinib (approved MEK1/2 inhibitor for melanoma; phase II for high-grade glioma) in primary and recurrent mesenchymal tumors was evaluated using an intracranial patient-derived tumor xenograft model, focusing on survival analysis.

Results
Our transcriptomic-kinomic integrative analysis revealed p38MAPK as the prime target whose gene signature enables patient stratification based on their molecular subtypes and provides prognostic value. Repurposed p38MAPK inhibitors synergize favorably with temozolomide to promote intracellular retention of temozolomide and exacerbate DNA damage. Mesenchymal cells exhibit adaptive chemoresistance to p38MAPK inhibition through a pH-/calcium-mediated MEK/ERK pathway. Dual p38MAPK and MEK inhibition effectively maintain temozolomide sensitivity in primary and recurrent intracranial mesenchymal glioblastoma xenografts.

Conclusions
Temozolomide resistance in mesenchymal glioblastoma is associated with p38MAPK activation. Adaptive chemoresistance in p38MAPK-resistant cells is mediated by MEK/ERK signaling. Adjuvant therapy with dual p38MAPK and MEK inhibition prolongs temozolomide sensitivity, which can be developed into a precision therapy for the mesenchymal subtype.
What do carers of people with high-grade glioma perceive could improve their preparedness to care, and what additional support do they require?
Authors: Clarke James J , Halkett Georgia K B , McDougall Emma , Dhillon Haryana M , Lobb Elizabeth , Phillips Jane L , Hudson Peter , Nowak Anna K 
Published: February 2024

Abstract

Background
Concerning levels of stress, strain, and poorer mental health are observed in family carers of patients diagnosed with high-grade glioma (HGG). Understanding the reported unmet needs of these carers will enable future interventions to address such needs to improve their preparedness for care and well-being. In this secondary analysis, we aimed to explore: (i) what carers of people with HGG perceive could improve their preparedness to care; and (ii) what needs carers reported they required additional support with.

Methods
Responses from 188 carers of patients with HGG participating in a randomized controlled trial of the Care-IS intervention were analyzed to identify reported unmet needs. Of this larger sample, 92 participants answered a qualitative question seeking to identify perceived unmet needs in carer preparedness over 12 months. These responses comprised the data for the current secondary analysis. Content analysis was used to analyze the qualitative data and observe trends across participant responses.

Results
Five overarching themes were identified: carer needs, providing emotional and practical care, coping with uncertainty, coping with the consequences of illness progression, and processing and supporting end-of-life care. Notably, the content analysis identified differences in response numbers between groups in the Care-IS trial, particularly with the control group having more needs regarding illness progression and end-of-life care.

Conclusions
Future interventions aimed at improving the well-being and preparedness of carers of people with HGG should consider providing better support centered on carer needs, their changed circumstances, living with uncertainty, and care transition.
Young Adults’ Exposure to and Engagement With Tobacco-Related Social Media Content and Subsequent Tobacco Use
Authors: Vogel Erin A , Barrington-Trimis Jessica L , Vassey Julia , Soto Daniel , Unger Jennifer B 
Published: February 2024

Abstract

Introduction
Nicotine/tobacco social media content may increase young people’s risk for use. This study examined prospective associations between exposure to and engagement with nicotine/tobacco-related social media content and nicotine/tobacco use among young adults.

Aims and Methods
Young adults (N = 2080) originally recruited from Southern California high schools for a prospective cohort study reported frequency of viewing and posting nicotine/tobacco content on four social media platforms (Facebook, Instagram, Twitter, and YouTube). Participants also reported frequency of seeing nicotine/tobacco posts from friends, seeing nicotine/tobacco posts from influencers or celebrities, and liking nicotine/tobacco posts. Within subsamples of nicotine/tobacco never users (n = 794), past users (n = 897) and current users (n = 389), analyses examined associations of baseline (May–October 2020) social media content exposure and engagement with follow-up (January–June 2021) tobacco use initiation (among never users), resumption (among past users), and continuation (among current users), adjusting for sociodemographic and socioenvironmental characteristics.

Results
Never users who saw nicotine/tobacco posts from friends (Adjusted Odds Ratio [AOR] = 2.91 [95% Confidence Interval [CI]: 1.46, 5.82], p = .002) or from celebrities or influencers (AOR = 2.77 [1.32, 5.84], p = .007) were significantly more likely to initiate nicotine/tobacco use than their peers. Among past users, posting nicotine/tobacco content at baseline was associated with use resumption (AOR = 1.77 [1.12, 2.80], p = .014). Content exposure and engagement were not associated with nicotine/tobacco use continuation among current users (p-values &gt; .05).

Conclusions
Seeing nicotine/tobacco posts from friends, influencers, or celebrities was associated with greater odds of tobacco use initiation, but not resumption or continuation, 6 months later. Young adults with past nicotine/tobacco use who post about nicotine/tobacco may be at elevated risk for resuming use.

Implications
Young adults with exposure to nicotine/tobacco social media content were more likely than their peers to initiate nicotine/tobacco use 6 months later. Past nicotine/tobacco users who reported posting about nicotine/tobacco on social media at baseline were more likely than their peers to resume nicotine/tobacco use. Among young adults with current nicotine/tobacco use at baseline, social media activity did not predict odds of nicotine/tobacco use continuation at follow-up. Nicotine/tobacco content on social media should be restricted to reduce young people’s chances of nicotine/tobacco use initiation or resumption.
Factors Associated With Abstinence Among Young Adult Smokers Enrolled in a Real-world Social Media Smoking Cessation Program
Authors: Lyu Joanne Chen , Meacham Meredith C , Nguyen Nhung , Ramo Danielle , Ling Pamela M 
Published: February 2024

Abstract

Objective
Social media platforms are promising to provide smoking cessation support. This study aimed to identify baseline factors associated with cigarette smoking abstinence among young adult smokers enrolled in a real-world social media-based smoking cessation program.

Aims and Methods
We analyzed data from young adult smokers (aged 18–30 years) participating in a publicly available Facebook-based smoking cessation program serving the San Francisco Bay Area. The analytic sample consisted of 248 participants who completed both the baseline and follow-up surveys at 3 months. Multivariable logistic regression analysis determined baseline factors significantly associated with self-reported 7-day cigarette smoking abstinence at 3 months.

Results
Participants were race/ethnically diverse, well-educated, and 47.6% reported LGB + sexual identity. Those who reported dual use of cigarettes and e-cigarettes in the past 30 days (vs. cigarette use only), current alcohol users (vs. non-users), and those aged 25–30 years (vs. 18–24 years) were significantly less likely to report 7-day abstinence at 3 months. Non-daily smokers (vs. daily smokers) and those with high desire to quit smoking (vs. low to moderate desire) were more likely to report abstinence. Results also showed reduction in the percentage of e-cigarette and other tobacco product use among participants.

Conclusions
Social media interventions may be more effective for young adult non-daily smokers and those with high desire to quit smoking. Smoking cessation programs may help reduce use of other tobacco products among treatment-seeking smokers. Smoking cessation interventions for young adults need to explicitly address dual use of cigarettes and e-cigarettes and use of alcohol.

Implications
Findings of this study highlight the need for future interventions to address dual use of cigarettes and e-cigarettes and use of alcohol to improve cigarette smoking abstinence outcomes. The reduction in the use of other tobacco products among program participants indicates that social media smoking cessation programs may exert a broader positive influence on overall tobacco consumption. The large number of LGB+ smokers participating in the program suggests social media is a promising cessation channel for this hard-to-reach group, warranting further study.
Using Computer Vision to Detect E-cigarette Content in TikTok Videos
Authors: Murthy Dhiraj , Ouellette Rachel R , Anand Tanvi , Radhakrishnan Srijith , Mohan Nikhil C , Lee Juhan , Kong Grace 
Published: February 2024

Abstract

Introduction
Previous research has identified abundant e-cigarette content on social media using primarily text-based approaches. However, frequently used social media platforms among youth, such as TikTok, contain primarily visual content, requiring the ability to detect e-cigarette-related content across large sets of videos and images. This study aims to use a computer vision technique to detect e-cigarette-related objects in TikTok videos.

Aims and Methods
We searched 13 hashtags related to vaping on TikTok (eg, #vape) in November 2022 and obtained 826 still images extracted from a random selection of 254 posts. We annotated images for the presence of vaping devices, hands, and/or vapor clouds. We developed a YOLOv7-based computer vision model to detect these objects using 85% of extracted images (N = 705) for training and 15% (N = 121) for testing.

Results
Our model’s recall value was 0.77 for all three classes: vape devices, hands, and vapor. Our model correctly classified vape devices 92.9% of the time, with an average F1 score of 0.81.

Conclusions
The findings highlight the importance of having accurate and efficient methods to identify e-cigarette content on popular video-based social media platforms like TikTok. Our findings indicate that automated computer vision methods can successfully detect a range of e-cigarette-related content, including devices and vapor clouds, across images from TikTok posts. These approaches can be used to guide research and regulatory efforts.

Implications
Object detection, a computer vision machine learning model, can accurately and efficiently identify e-cigarette content on a primarily visual-based social media platform by identifying the presence of vaping devices and evidence of e-cigarette use (eg, hands and vapor clouds). The methods used in this study can inform computational surveillance systems for detecting e-cigarette content on video- and image-based social media platforms to inform and enforce regulations of e-cigarette content on social media.
Evaluating The Real Cost Digital and Social Media Campaign: Longitudinal Effects of Campaign Exposure on E-cigarette Beliefs
Authors: MacMonegle Anna , Bennett Morgane , Speer Jessica L , O’Brien Erin Keely , Pitzer Lindsay , Jaarsma Allie , Nguyen Zarndt Anh , Duke Jennifer 
Published: February 2024

Abstract

Introduction
Over the past decade, youth e-cigarette use has risen exponentially. At the same time, digital media use increased markedly while the use of traditional broadcast TV declined. In response, the U.S. Food and Drug Administration’s The Real Cost public education campaign shifted to communicating the harms of e-cigarette via primarily digital and social platforms. This study evaluated longitudinal associations between exposure to campaign advertisements and changes in campaign-specific beliefs among US youth.

Methods
A nationally representative longitudinal cohort of youth (aged 11–16 years at baseline) was surveyed five times. Building on earlier work, we analyzed data from the last three waves (April–July 2020; January–April 2021; and August–October 2021; N = 2625). We assessed self-reported exposure to six ads and agreement with 11 beliefs that were each targeted by one or more ads. Eleven weighted panel regression models assessed whether ad exposure predicted changes in campaign-specific beliefs over time.

Results
We observed significant associations between ad exposure and increases in at least one campaign-specific belief for five of the six ads. Across the 11 beliefs, we observed associations between increased exposure and increases in 6 beliefs related to e-cigarettes and toxic metals, lung damage, dangerous ingredients, anxiety, cigarette use, and disappointing important people.

Conclusions
We found evidence that self-reported exposure to this digital and social media campaign was successful at influencing youth, providing support for the effectiveness of the campaign’s adaption to address youth’s changes in tobacco and media use habits.

Implications
The Food and Drug Administration’s The Real Cost public education campaign educates youth about the dangers of e-cigarette use. This study evaluates longitudinal associations between exposure to The Real Cost’s advertisements and changes in campaign-specific beliefs among youth. Considering evolving trends in youth media consumption, the campaign adapted its media approach to increase delivery across digital and social media platforms. Our findings indicate that the campaign reached its intended audience and increased youth beliefs around the harm of e-cigarettes and the consequences of e-cigarette use, offering evidence for the effectiveness of digital and social media youth prevention efforts within a fragmented digital environment.