bluuebunny/crossref_metadata_2025 huggingface dataset:
Boosting the Sensitivity of Quantitative Single-Cell Proteomics with Activated lon-Tandem Mass Tags (AI-TMT)
Authors: Peters-Clarke Trenton M. , Liang Yiran , Mertz Keaton L. , Lee Kenneth W. , Westphall Michael S. , Hinkle Joshua D. , McAlister Graeme C. , Syka John E. P. , Kelly Ryan T. , Coon Joshua J.
Published: February 2024

Single-cell proteomics is a powerful approach to precisely profile protein landscapes within individual cells toward a comprehensive understanding of proteomic functions and tissue and cellular states. The inherent challenges associated with limited starting material in single-cell analyses demands heightened analytical sensitivity. Just as advances in sample preparation maximize the amount of material that makes it from the cell to the mass spectrometer, we strive to maximize the number of ions that make it from ion source to the detector. In isobaric tagging experiments, limited reporter ion generation limits quantitative accuracy and precision. The combination of infrared photoactivation and ion parking circumvents them/zdependence inherent in HCD, maximizing reporter generation and avoiding unintended degradation of TMT reporter molecules in a method we term activated ion-tandem mass tags (AI-TMT). The method was applied to single-cell human proteomes using 18-plex TMTpro, resulting in a 4-5-fold increase in reporter ion signal on average compared to conventional SPS-MS3approaches. AI-TMT enables faster duty cycles, higher throughput, and increased peptide identification and quantification. Comparative experiments showcase 4-5-fold lower injection times for AI-TMT, providing superior sensitivity without compromising accuracy. In all, AI-TMT enhances the sensitivity and dynamic range of proteomic experiments and is compatible with other techniques, including gas-phase fractionation and real-time searching, promising increased gains in the study of cellular heterogeneity and disease mechanisms.
Stress pathway outputs are encoded by pH-dependent phase separation of its components
Authors: Didan Yuliia , Ghomlaghi Milad , Nguyen Lan K. , Ng Dominic C. H.
Published: February 2024

Signal processing by intracellular kinases control near all biological processes but how precise functions of signal pathways evolve with changed cellular contexts is poorly understood. Functional specificity of c-Jun N-terminal Kinases (JNK) activated in response to a broad range of pathological and physiological stimuli are partly encoded by signal strength. Here we reveal that intracellular pH (pHi) is a significant component of the JNK regulatory network and defines JNK signal response to precise stimuli. We showed that nuanced fluctuations in physiological pHi regulates JNK activity in response to cell stress. Interestingly, the relationship between pHi and JNK activity was dependent on specific stimuli and upstream kinases involved in pathway activation. Cytosolic alkalinisation promoted phase transition of upstream ASK1 to augment JNK activation. While increased pHi similarly induced JNK2 to form condensates, this led to attenuated JNK activity. Mathematical modelling of feedback signalling incorporating pHi and differential contribution by JNK2 and ASK1 condensates was sufficient to delineate the strength of JNK signal response to specific stimuli. This new knowledge of pHi regulation with consideration of JNK2 and ASK1 contribution to signal transduction may delineate oncogenic versus tumour suppressive functions of the JNK pathway and cancer cell drug responses.
Mechanistic dissection of theCHD4enhancers reveals cooperative functions among the homotypic ZNF410 clustered motifs
Authors: Xu Siyuan , Ren Ren , Peng Chuxuan , Lu Haowen , Ly Lana C. , Crossley Merlin , Xu Bin , Cheng Xiaodong , Blobel Gerd A. , Lan Xianjiang
Published: February 2024

Transcription factors often regulate numerous target genes. However, ZNF410 controls only a single gene,CHD4,in human erythroid cells by its highly restricted chromatin occupancy to theCHD4locus via two clusters of ZNF410 binding motifs. Here, we uncover that ZNF410 controls chromatin accessibility and activity of the twoCHD4enhancer regions. Combining CRISPR/Cas9 genomic deletion with CRISPRi approaches, we demonstrate that both enhancer regions additively contribute toCHD4gene expression. Mutations of the di-adenine nucleotides within the ZNF410 binding motif fully disrupt ZNF410-DNA interaction. Luciferase assays, ChIP-seq, and ATAC-seq studies reveal that the homotypic clustered motifs within theCHD4enhancers are recognized by ZNF410 in a collaborative fashion. Especially, the three ZNF410 motifs located in the 3’ end of the distal enhancer act as “switch motifs” to control the chromatin accessibility and activity of the whole distal enhancer region. Together, our findings expose a complex functional hierarchy of motifs, where clustered motifs bound by the same transcription factor cooperate to fine-tune the expression of target gene.

Highlights

ZNF410 maintains the accessibility of theCHD4enhancer regions

The two enhancer elements additively modulateCHD4gene expression

The dinucleotide “AA” is the key bases within ZNF410 binding motif

ZNF410 binds to homotypic clustered motifs in a cooperative manner
The role of viral interference in shaping RSV epidemics following the 2009 H1N1 influenza pandemic
Authors: Li Ke , Thindwa Deus , Weinberger Daniel M , Pitzer Virginia E
Published: February 2024

Background

Disruptions in respiratory syncytial virus (RSV) activity were observed in different countries following the 2009 influenza pandemic. Given the limited use of non-pharmaceutical interventions, these disruptions do provide an opportunity to probe viral interference due to the out-of-season epidemics. The objectives of the study are twofold: to characterize atypical RSV activity in the United States (US) and to explore the mechanisms underlying changes in RSV epidemics following the pandemic.

Methods

Laboratory-confirmed RSV cases across 10 US regions from June 2007 to July 2019 were analyzed. A dynamic time warping method was used to characterize RSV activity in different seasons. A two-pathogen model was constructed to explore viral interference mechanisms. A sampling-importance resampling method was applied to estimate the effects of viral interference.

Results

We found that RSV activity was reduced following the influenza pandemic in the 2009/10 season across all regions in the US. By contrast, we found an enhanced but delayed RSV epidemic across the US in the 2010/11 season. Using a mathematical model, we identified three potential viral interference mechanisms that could explain the change of RSV activity following the pandemic. The pandemic influenza may interfere with RSV to reduce susceptibility to RSV coinfection, or shorten the RSV infectious period, or decrease RSV infectivity in co-infections.

Conclusions

This study provides statistical evidence for atypical RSV seasons following the influenza pandemic in the US and sheds light on viral interference mechanisms affecting RSV epidemics, offering a model-fitting framework for analyzing surveillance data at the population level.
Investigating brain dynamics and their association with cognitive control in opioid use disorder using naturalistic and drug cue paradigms
Authors: Ye Jean , Mehta Saloni , Peterson Hannah , Ibrahim Ahmad , Saeed Gul , Linsky Sarah , Kreinin Iouri , Tsang Sui , Nwanaji-Enwerem Uzoji , Raso Anthony , Arora Jagriti , Tokoglu Fuyuze , Yip Sarah W. , Hahn C. Alice , Lacadie Cheryl , Greene Abigail S. , Constable R. Todd , Barry Declan T. , Redeker Nancy S. , Yaggi Henry , Scheinost Dustin
Published: February 2024

Objectives

Opioid use disorder (OUD) impacts millions of people worldwide. The prevalence and debilitating effects of OUD present a pressing need to understand its neural mechanisms to provide more targeted interventions. Prior studies have linked altered functioning in large-scale brain networks with clinical symptoms and outcomes in OUD. However, these investigations often do not consider how brain responses change over time. Time-varying brain network engagement can convey clinically relevant information not captured by static brain measures.

Methods

We investigated brain dynamic alterations in individuals with OUD by applying a new multivariate computational framework to movie-watching (i.e., naturalistic; N=76) and task-based (N=70) fMRI. We further probed the associations between cognitive control and brain dynamics during a separate drug cue paradigm in individuals with OUD.

Results

Compared to healthy controls (N=97), individuals with OUD showed decreased variability in the engagement of recurring brain states during movie-watching. We also found that worse cognitive control was linked to decreased variability during the rest period when no opioid-related stimuli were present.

Conclusions

These findings suggest that individuals with OUD may experience greater difficulty in effectively engaging brain networks in response to evolving internal or external demands. Such inflexibility may contribute to aberrant response inhibition and biased attention toward opioid-related stimuli, two hallmark characteristics of OUD. By incorporating temporal information, the current study introduces novel information about how brain dynamics are altered in individuals with OUD and their behavioral implications.
School children’s oral health status, behaviours, and dental care utilization: the case of a northern Thailand elementary school
Authors: Pattanaporn Komkham , Kawong Warathaya , Wongwanichwattana Wassana , Chomphrom Kulnan , Chakkathamanukul Natchaphon , Kamsiriphiman Nalinporn , Prasomphon Panithi , Saksurasap Pitchaya , Nilniyom Pansuk , Brondani Mario
Published: February 2024

Background

Although preventable, dental caries remain a serious global public health threat. There are a number of risk factors for the development of dental caries in the general population, and in elementary school children in Thailand in particular, especially if they are from suburban areas.

Objective

To identify the prevalence of dental caries in the form of decayed-missing-filled teeth for the permanent (DMFT) and primary (dmft) dentition, and their risk factors among children between 6 and 12 years of age attending a public school in Chiang Rai in northern Thailand.

Methods

A cross-sectional study was conducted among 6–12-year-old children attending public education at Thesaban 1 School, Chiang Saen District, Chiang Rai Province in Thailand. All school children from grades 1 to 6 were examined by trained dental students from Mae Fah Luang University’s School of Dentistry in December 2023. Children were clinically examined for DMFT/dmft while demographic information about the children was collected from school records. Children also responded to a standardized 17-item survey about their oral health care behaviours. Descriptive and inferential statistics were used. All tests were set at 95% CI andp>0.05.

Results

A total of 232 children (100% of eligible participants) were examined and 96 (40%) responded to the survey. Most children were Buddhists (n=186, 80.1%), and had at least one permanent tooth with sealant (n=198, 85.3%); 82.5% of the 232 children exhibited dental caries/extraction/fillings in primary teeth. The average dmft was 4.1 (1.8–8.8) and the average DMFT was 1.6 (0.1–3.3). Fifty children (21.5%) had their grandparents as their main caregiver. Children who brushed their teeth without fluoridated toothpaste were 1.99 times more likely to have at least 1 permanent tooth with dental decay than children who used fluoridated toothpaste (p=0.065).

Conclusion

In this study, a high percentage of dental caries was observed among children from suburban areas in the northernmost province of Thailand. Public health intervention and oral health promotion remain an immediate need among these children.
Factors associated with Low birth weight in Cambodia: A secondary analysis of Cambodia Demographic and Health Survey, 2021-2022
Authors: Um Samnang , Sok Sakha , Leng Dany
Published: February 2024

Low birth weight (LBW) is a serious global health concern, including in Cambodia. It is associated with a higher risk of neonatal, infant, and under-five mortality and morbidity. We examined the prevalence of LBW across provinces and factors associated with LBW among newborns in Cambodia. We analyzed the most recent children’s data from the Cambodia Demographic and Health Survey (CDHS) 2021-2022. There were 4,565 weighted newborns included in this study. The provincial variation in the prevalence of LBW was done using ArcGIS. Multiple logistic regression analyses were conducted to assess factors independently associated with LBW. The prevalence of LBW was 5.9% (95% CI: 5.2–6.8), which was highest in Ratanak Kiri (13.9%), Kratie (12.8%), Pailin (12.7%), and Svay Rieng (10.2%). Factors were independently associated with LBW, including mothers with primary education (AOR = 1.82; 95% CI: 1.09–3.04), unemployed (AOR = 1.62; 95% CI: 1.03–2.55), being a first-born child (AOR = 1.74; 95% CI: 1.24–2.45), born to mothers in rural areas (AOR = 1.42; 95% CI: 1.00–2.01). However, mothers who attended at least 4 ANC visits had lower odds of LBW (AOR = 0.65; 95% CI: 0.47–0.91). The prevalence of LBW among newborns in Cambodia is lower than in Southsea Asia and worldwide. However, provincial variations in the prevalence of LBW were high in remote areas. Public Health programs should target provinces where LBW prevalence remains high. Cambodia policy continues to recommend four or more ANC visits to pregnant women, particularly those who have limited education and live in rural areas.
EmbB and EmbC Regulate the Sensitivity ofMycobacterium abscessusto Echinomycin
Authors: He Jing , Gao Yamin , Wang Jingyun , Hameed H.M. Adnan , Wang Shuai , Fang Cuiting , Tian Xirong , Zhang Jingran , Han Xingli , Ju Yanan , Tan Yaoju , Ma Junying , Ju Jianhua , Hu Jinxing , Liu Jianxiong , Zhang Tianyu
Published: February 2024

Treatment ofMycobacterium abscessus(Mab) infection is a major challenge due to its intrinsic resistance to most available drugs. It is thus imperative to find new anti-Mab drugs. In this study, we investigated the activity and intrinsic resistance mechanism of echinomycin (ECH) against Mab. ECH is active against Mab (MIC: 2 µg/mL). TheembCgene knockout strain (MabΔembC) showed hyper-sensitive to ECH (MIC: 0.0078-0.0156 µg/mL). The MICs of ECH-resistant strains screened based on the MabΔembCstrain were 0.25-1 µg/mL. Mutations were found in the EmbB, including Asp306Ala, Asp306Asn, Arg350Gly, Val555Ile, and Gly581Ser, which led to increased resistance to ECH when overexpressed in MabΔembCindividually (0.25-0.5 µg/mL). The EmbB mutants edited by the CRISPR/Cpf1 system became more resistant to ECH (MIC: 0.25-0.5 µg/mL). The permeability of gene-edited and overexpressed Mab strains was reduced, as shown by the ethidium bromide accumulation assay, but it was still significantly higher than that of the parent Mab. To summarize, our study demonstrates that ECH has a strong anti-Mab activity and confirms that EmbB and EmbC are related to the sensitivity of Mab to ECH. EmbB mutation may partially compensate for the function of EmbC.

Impact Statement

Mycobacterium abscessus(Mab) is a rapidly growing, intrinsic multidrug-resistant Mycobacterium. This study demonstrated that echinomycin (ECH) has potent antibacterial activity against Mab, and the mechanism of ECH resistance to Mab is related to EmbB and EmbC. EmbB and EmbC can alter the sensitivity of Mab to ECH by altering the permeability of its cell wall. In addition, there is a functional complementary evolution between EmbB and EmbC to regulate sensitivity to ECH. Overall, our study provides a novel anti-Mab drug candidate ECH and a scientific foundation for developing effective strategies to prevent and control Mab.
The sea urchin intestinal microbiome responds dynamically to food intake and contains nitrogen-fixing symbionts
Authors: Bengtsson Mia M. , Helgesen Marita , Wang Haitao , Fredriksen Stein , Norderhaug Kjell Magnus
Published: February 2024

Kelp deforestation by sea urchin grazing is a widespread phenomenon globally, with vast consequences for coastal ecosystems. The ability of sea urchins to survive on a kelp diet of poor nutritional quality is not well understood and bacterial communities in the sea urchin intestine may play an important role in digestion. A no-choice feeding experiment was conducted with the sea urchinStrongylocentrotus droebachiensis, offering three different seaweeds as diet, including the kelpSaccharina latissima. Starved sea urchins served as experimental control. Amplicons of the 16S rRNA gene were analyzed from fecal pellets. One dominant symbiont (Psychromonas marina) accounted for 44 % of all sequence reads and was especially abundant in the sea urchins fed seaweed diets. The starved and field captured sea urchins consistently displayed higher diversity than the seaweed-fed sea urchins and displayed a higher predicted abundance of genes involved in nitrogen fixation. Cloning and sequencing of the NifH gene revealed diverse nitrogen fixers. We demonstrate that the sea urchin intestinal microbiome is dynamic, responds to diet and has the capacity for nitrogen fixation. The microbiome thereby reflects the dietary flexibility of these sea urchins, and could be a key component in understanding catastrophic kelp forest grazing events.
High performance TadA-8e derived cytosine and dual base editors with undetectable off-target effects in plants
Authors: Fan Tingting , Cheng Yanhao , Wu Yuechao , Liu Shishi , Tang Xu , He Yao , Liao Shanyue , Zheng Xuelian , Zhang Tao , Qi Yiping , Zhang Yong
Published: February 2024

Cytosine base editors (CBEs) and adenine base editors (ABEs) are powerful tools to install precise C-to-T and A-to-G base edits in living organisms. In recently years, a highly efficient ABE based on engineered TadA-8e, known as ABE8e, has been developed to confer highly efficient A-to-G editing in mammalian cells and plants. Interestingly, TadA-8e can be further evolved and engineered to confer cytosine base editing. In this study, we compare in rice and tomato cells a serial of engineered CBEs derived from TadA-8e and identify TadCBEa, TadCBEd, and TadCBEd_V106W as efficient CBEs with high editing purity, while maintaining the relatively narrow editing window of ABE8e. Excitingly, we show TadDE is a new class of dual base editor where a single deaminase domain promotes simultaneous C-to-T and A-to-G base editing in plant cells. Multiplexed base editing is demonstrated in transgenic rice plants with TadCBEa and TadDE. Furthermore, no off-target effects of TadCBEa and TadDE can be detected by whole genome and transcriptome sequencing of the transgenic lines, suggesting high editing specificity. Finally, we demonstrate two gain-of-function crop engineering applications in rice by using the efficient dual base editor, TadDE. In the first case, herbicide resistance alleles ofOsALSare introduced by TadDE. In the second case, synonymous mutations are generated inOsSPL14, making its transcript resistant toOsMIR156-mediated degradation. Together, this study reports TadA-8e derived CBEs and a dual base editor with high editing activity, purity, and specificity. They are valuable additions to the expanding plant base editing toolbox.
Predictive and error coding for vocal communication signals in the songbird auditory forebrain
Authors: Rudraraju Srihita , Turvey Michael E. , Theilman Bradley H. , Gentner Timothy Q.
Published: February 2024

Predictive coding posits that sensory signals are compared to internal models, with resulting prediction-error carried in the spiking responses of single neurons. Despite its proposal as a general cortical mechanism, including for speech processing, whether or how predictive coding functions in single-neuron responses to vocal communication signals is unknown. As a proxy internal model, we developed a neural network that uses current sensory context to predict future spectrotemporal features of a vocal communication signal, birdsong. We then represent birdsong as either weighted sets of latent predictive features evolving in time, or as time-varying prediction-errors that reflect the difference between ongoing network-predicted and actual song. Using these spectrotemporal, predictive, and prediction-error song representations, we fit linear/non-linear receptive fields to single neuron responses recorded from caudomedial nidopallium (NCM), caudal mesopallium (CMM) and Field L, analogs of mammalian auditory cortices, in anesthetized European starlings,Sturnus vulgaris, listening to conspecific songs. In all three regions, the predictive features of song yield the single best model of song-evoked spiking responses, but unique information about all three representations (signal, prediction, and error) is carried in the spiking responses to song. The relative weighting of this information varies across regions, but in contrast to many computational predictive coding models neither predictive nor error responses are segregated in separate neurons. The continuous interplay between prediction and prediction-error is consistent with the relevance of predictive coding for cortical processing of temporally patterned vocal communication signals, but new models for how prediction and error are integrated in single neurons are required.
KoRV-related retroviruses in diverse Australian and African rodent species
Authors: Hayward Joshua A. , Tachedjian Gilda
Published: February 2024

The koala retrovirus (KoRV) is a key contributor to the ongoing decline of Australia’s koala population. KoRV has only been found in koalas and its enigmatic origins, as well as that of its close relative, the gibbon ape leukemia virus (GALV), have been a source of enduring debate. Bats and rodents are each proposed as major reservoirs of interspecies transmission with ongoing efforts to identify additional animal hosts of KoRV-related retroviruses. In this study we identified nine rodent species as novel hosts of KoRV-related retroviruses. Included among these hosts are two African rodents, revealing the first appearance of this clade beyond the Australian and Southeast Asian region. One of these African rodents,Mastomys natalensis, carries an endogenous KoRV-related retrovirus that is fully intact and potentially still infectious. Our findings suggest that rodents are the major carriers of KoRV-related retroviruses, with a potential point of origin in Southeast Asia.
Centromedian thalamic deep brain stimulation for idiopathic generalized epilepsy – case series and target analysis
Authors: Park Sihyeong , Agashe Shruti , Osman Gamaleldin , Simpson Hugh D. , Miller Kai J. , Van Gompel Jamie J. , Starnes Keith , Lundstrom Brian N. , Worrell Gregory A. , Gregg Nicholas M.
Published: February 2024

Introduction

There is a lack of treatment options for individuals with drug resistant idiopathic generalized epilepsy (IGE). Small, limited case series suggest that centromedian thalamus deep brain stimulation (CM-DBS) may be an effective treatment option. The optimal CM-DBS target for IGE is underexamined. Here, we present a retrospective analysis of CM-DBS targeting and efficacy for five patients with drug-resistant IGE.

Methods

This single-center case series study included all patients with drug resistant IGE treated with CM-DBS to date. Seizure outcomes were measured with patient-reported seizure frequency. Baseline frequency was taken from the visit immediately before implantation, and it was compared with the seizure frequency from the most recent visit. Stimulation parameters from last clinic visit were used to determine the volume of tissue activated (VTA) by DBS. Lead proximity to target, and VTA overlap with CM nucleus was performed using an open-source toolbox (Lead-DBS 3.0, SimBio/FieldTrip). Associations between the intersection of the VTA and CM nucleus, and seizure outcomes were measured using Spearman’s rank correlation.

Results

Five patients were identified and included in the study. Median age was 31 (22-45). Median baseline frequency of convulsive seizure was 1.5 per month (0-3.5). Median follow-up time was 13 months (3-23). Median convulsive seizure frequency reduction was 60% (−200-100%). One patient had only absence seizures, with >99% absence seizure frequency reduction. Four out of five subjects had electrode contacts positioned within the CM nucleus target, all of whom had >50% reduction in primary semiology seizure frequency (3 subjects with convulsive seizures, 1 patient with absence seizures). Spearman’s rho was 0.90 (P=0.025). Volumetric “sweet-spot” mapping revealed best outcomes were correlated with stimulation of the middle ventral CM nucleus.

Conclusion

Our findings suggest that CM-DBS can be an effective treatment for patients with IGE. The extent of overlap between the VTA by DBS and CM nucleus is correlated with the degree of seizure reduction, highlighting the importance of accurate targeting and volumetric targeting analysis.
Proteomics data in vitiligo: a scoping review
Authors: Berrevoet Danique , Van Nieuwerburgh Filip , Deforce Dieter , Speeckaert Reinhart
Published: February 2024

An unbiased screening of which proteins are deregulated in vitiligo using proteomics can offer an enormous value. It could not only reveal robust biomarkers for detecting disease activity but can also identify which patients are most likely to respond to treatments. We performed a scoping review searching for all articles using proteomics in vitiligo. Eight manuscripts could be identified. Unfortunately, very limited overlap was found in the differentially expressed proteins between studies (15 out of 272; 5,51%) with variable degrees of the type of proteins and a substantial variety in the prevalence of acute phase proteins (range: 6-65%). Proteomics research has therefore brought little corroborating evidence on which proteins are differentially regulated between vitiligo patients and healthy controls or between active and stable vitiligo patients. While a limited patient size is an obvious weakness for several studies, an incomplete description of patient characteristics is an unfortunate and avoidable shortcoming. Additionally, the variations in the used methodology and analyses may further contribute to the overall observed variability. Nonetheless, more recent studies investigating the response to treatment seem to be more robust, as more differentially expressed proteins that have previously been confirmed to be involved in vitiligo were found. The further inclusion of proteomics analyses in clinical trials is recommended to increase insights into the pathogenic mechanisms in vitiligo and identify reliable biomarkers or promising drug targets. A harmonization in the study design, reporting and proteomics methodology could vastly improve the value of vitiligo proteomics research.
Patterns of blunt and cigar use in the United States, 2015-2019
Authors: Jensen Jessica K , Ganz Ollie , Tomaino Marisa , Glasser Allison M , Sterling Kymberle , Delnevo Cristine D , Bover Manderski Michelle T
Published: February 2024

Background

The use of cigars for blunts (i.e., cannabis rolled in cigar paper) is well-documented; proportions of cigar and blunt use and associated characteristics are less studied.

Methods

Pooled data from the 2015-2019 National Survey on Drug Use and Health (NSDUH) were analyzed in 2023. Respondents aged 12+ who reported past 30-day cigar use were categorized into three mutually exclusive use categories: (1) exclusively cigars, (2) exclusively blunts, and (3) both cigars and blunts. We examined associations between cigar-blunt use category and sociodemographic characteristics.

Results

Among people 12 and older who reported past 30-day cigar use, 48.6% (95% CI=47.6-49.6) reported exclusive cigar use; 44.3% (95% CI=43.3-45.3) reported exclusive blunt use; and 7.2% (95% CI=6.8-7.6) reported cigars and blunts. The prevalence differed by age, with exclusively blunts most prevalent among youth (72.5% [95% CI=70.7-74.3]) and young adults (62.4% [95% CI=61.4-63.5]), and exclusively cigars most prevalent among adults 26+ (61.2% [95% CI=59.8-62.5]). Exclusive blunt users smoked more days in the past month (17.5; 95% CI=16.8-18.2), compared to 13.8 days (95% CI=13.2-14.4) for cigar and blunt users, and 7.7 days (95% CI=7.5-8.0) for exclusive cigar users. There were significant differences in characteristics, with exclusive blunt use more prevalent among female (41.6%; 95% CI=40.3-42.9) and Hispanic (18.2%; 95% CI=17.3-19.2) participants.

Conclusions

Exclusive blunt use was the most prevalent pattern of past-30-day cigar use among youth and young adults. Those who use cigars as blunts smoke more cigars per month, suggesting this may be an important group for additional education and policy efforts.
Global Assessment of Palliative Care Need: Serious Health-Related Suffering Measurement Methodology
Authors: Kwete Xiaoxiao J , Bhadelia Afsan , Arreola-Ornelas Héctor , Mendez Oscar , Rosa William E. , Connor Stephen , Downing Julia , Jamison Dean , Watkins David , Calderon Renzo , Cleary Jim , Friedman Joe , De Lima Liliana , Ntizimira Christian , Pastrana Tania , Pérez-Cruz Pedro E. , Spence Dingle , Rajagopal M.R. , Enciso Valentina Vargas , Krakauer Eric L. , Radbruch Lukas , Knaul Felicia Marie
Published: February 2024

Inequities and gaps in palliative care access are a serious impediment to health systems especially low- and middle-income countries and the accurate measurement of need across health conditions is a critical step to understanding and addressing the issue. Serious Health-related Suffering (SHS) is a novel methodology to measure the palliative care need and was originally developed by The Lancet Commission on Global Access to Palliative Care and Pain Relief. In 2015, the first iteration – SHS 1.0 – was estimated at over 61 million people worldwide experiencing at least 6 billion days of SHS annually as a result of life-limiting and life-threatening conditions. In this paper, an updated methodology - SHS2.0 - is presented building on the work of the Lancet Commission and detailing calculations, data requirements, limitations, and assumptions. The updates to the original methodology focus on measuring the number of people who die with (decedents) or live with (non-decedents) SHS in a given year to assess the number of people in need of palliative care across health conditions and populations. Detail on the methodology for measuring the number of days of SHS that was pioneered by the Lancet Commission, is also shared, as this second measure is essential for determining the health system responses that are necessary to address palliative care need and must be a priority for future methodological work on SHS. The discussion encompasses opportunities for applying SHS to future policy making assessment of future research priorities particularly in light of the dearth of data from low- and middle-income countries, and sharing of directions for future work to develop SHS 3.0.
Zebrafish and cellular models ofSELENON-Related Myopathy exhibit novel embryonic and metabolic phenotypes
Authors: Barraza-Flores Pamela , Moghadaszadeh Behzad , Lee Won , Isaac Biju , Sun Liang , Troiano Emily C. , Rockowitz Shira , Sliz Piotr , Beggs Alan H.
Published: February 2024

SELENON-Related Myopathy (SELENON-RM) is a rare congenital myopathy caused by mutations of theSELENONgene characterized by axial muscle weakness and progressive respiratory insufficiency. Muscle histopathology commonly includes multiminicores or a dystrophic pattern but is often non-specific. TheSELENONgene encodes selenoprotein N (SelN), a selenocysteine-containing redox enzyme located in the endo/sarcoplasmic reticulum membrane where it colocalizes with mitochondria-associated membranes. However, the molecular mechanism(s) by which SelN deficiency causesSELENON-RM are undetermined. A hurdle is the lack of cellular and animal models that show assayable phenotypes. Here we report deep-phenotyping of SelN-deficient zebrafish and muscle cells. SelN-deficient zebrafish exhibit changes in embryonic muscle function and swimming activity in larvae. Analysis of single cell RNAseq data in a zebrafish embryo-atlas revealed coexpression betweenselenonand genes involved in glutathione redox pathway. SelN-deficient zebrafish and mouse myoblasts exhibit changes in glutathione and redox homeostasis, suggesting a direct relationship with SelN function. We report changes in metabolic function abnormalities in SelN-null myotubes when compared to WT. These results suggest that SelN has functional roles during zebrafish early development and myoblast metabolism.
Prioritizing Maize Metabolic Gene Regulators through Multi-Omic Network Integration
Authors: Gomez-Cano Fabio , Rodriguez Jonas , Zhou Peng , Chu Yi-Hsuan , Magnusson Erika , Gomez-Cano Lina , Krishnan Arjun , Springer Nathan M , de Leon Natalia , Grotewold Erich
Published: February 2024

Elucidating gene regulatory networks is a major area of study within plant systems biology. Phenotypic traits are intricately linked to specific gene expression profiles. These expression patterns arise primarily from regulatory connections between sets of transcription factors (TFs) and their target genes. Here, we integrated 46 co-expression networks, 283 protein-DNA interaction (PDI) assays, and 16 million SNPs used to identify expression quantitative trait loci (eQTL) to construct TF-target networks. In total, we analyzed ∼4.6M interactions to generate four distinct types of TF-target networks: co-expression, PDI,trans-eQTL, andcis-eQTL combined with PDIs. To functionally annotate TFs based on their target genes, we implemented three different network integration strategies. We evaluated the effectiveness of each strategy through TF loss-of function mutant inspection and random network analyses. The multi-network integration allowed us to identify transcriptional regulators of several biological processes. Using the topological properties of the fully integrated network, we identified potential functionally redundant TF paralogs. Our findings retrieved functions previously documented for numerous TFs and revealed novel functions that are crucial for informing the design of future experiments. The approach here-described lays the foundation for the integration of multi-omic datasets in maize and other plant systems.

GRAPHICAL ABSTRACT
Temporal Analysis of Pituitary Transcriptional Dynamics in Mice Models of Hypopituitarism During Postnatal Development
Authors: Marques Juliana Moreira , Chang Claudia Veiga , Souza Trigueiro Nicholas Silvestre , Araujo Ricardo Vieira , dos Santos Cerqueira Cinthya , Russo Lilian Cristina , Azevedo Bruna Viscardi , de Mendonca Berenice Bilharinho , Hoch Nicolas , de Carvalho Luciani Renata Silveira
Published: February 2024

Congenital hypopituitarism is characterized by deficient pituitary hormone production, affecting growth and development. The molecular mechanisms underlying pituitary development and dysfunction in hypopituitarism remain incompletely understood. We investigated the expression of key pituitary development markers in three mouse models of congenital hypopituitarism, with molecular alterations in theProp1, Pou1f1, andαGSUgenes across critical postnatal developmental stages: neonatal (P0), early postnatal (P7), pubertal (4 weeks), and adult (8 weeks). We assessed mRNA and protein levels of the pituitary stem cell markers (SOX2), proliferation marker (Ki67) and pituitary hormones, correlating these with pituitary function and disease.Prop1deficiency led to significant upregulation ofSox2andHesx1during early postnatal development and in adulthood, diverging from the relatively stable expression patterns observed inPou1f1andαGSUmutants. Despite some variations, overallSox2andKi67expression profiles were similar betweenProp1andPou1f1mutants.Prop1mutants exhibited altered pituitary morphology, with increased SOX2-positive cells suggesting disrupted stem cell migration. During the pubertal period, a subset of hormone-producing cells inProp1mutants co-expressed SOX2, indicating differentiation without restoring normal pituitary function. Hormone analysis revealed transient gonadotropin production and secretion during sexual maturation inProp1mutants, without recovery of the hypogonadal phenotype. Our study elucidates the complex transcriptional dynamics of pituitary development markers in mouse models of congenital hypopituitarism, highlighting the pivotal role ofProp1in regulating stem cell marker expression. The distinct transcriptional responses inProp1mutants during key developmental windows shed light on the mechanisms of pituitary dysgenesis and the persistent inability to fully recover pituitary function, despite transient hormonal changes during puberty. These insights contribute to a better understanding of pituitary development and dysfunction in congenital hypopituitarism.
The spatiotemporal dynamics of bottom-up and top-down processing during at-a-glance reading
Authors: Flower Nigel , Pylkkänen Liina
Published: February 2024

Like all domains of cognition, language processing is affected by top-down knowledge. Classic evidence for this is missing blatant errors in the signal. In sentence comprehension, one instance of this is failing to notice word order errors, such as transposed words in the middle of a sentence:you that read wrong(Mirault et al., 2018). Our brains seem to fix such errors, since they are incompatible with our grammatical knowledge. But how do our brains do this? Following behavioral work on inner transpositions, we flashed four-word sentences for 300ms using rapid parallel visual presentation (RPVP, Snell and Grainger, 2017). We compared their magnetoencephalography responses to fully grammatical and reversed sentences. Left lateral language cortex robustly distinguished grammatical and reversed sentences starting at 213ms. Thus, the influence of grammatical knowledge begun rapidly after visual word form recognition (Tarkiainen et al., 1999). At the earliest stage of this neural “sentence superiority effect,” inner transpositions patterned between grammatical and reversed sentences, showing evidence that the brain initially “noticed” the error. However, a hundred millisecond later, the inner transpositions became indistinguishable from the grammatical sentences, suggesting that at this point, the brain had “fixed” the error. These results show that after a single glance at a sentence, syntax impacts our neural activity almost as quickly as higher-level object recognition is assumed to take place (Cichy et al., 2014). The earliest stage involves a detailed comparison between the bottom-up input and grammatical knowledge, while shortly afterwards, knowledge can override an error in the stimulus.
Novel transcriptional activator TAC3 regulates age-dependent floral transition in Chinese fir (Cunninghamia lanceolata)
Authors: Wu Qiyao , Li Jian , Zhu Tengfei , Chang Huang , Wang Xu , Su Jun
Published: February 2024

Plant undergo juvenile-to-adult transition to become competent for age-dependent floral induction and reproductive transition, which is of great significance for improving the seed quality and maintaining desirable genetic traits of Chinese fir, but the underlying molecular mechanize still remains unknown. Here, we investigated the function of our newly identified spermatophyte specific transcriptional co-activator TAC3 (Transcriptional Activator in Chinese fir 3) and its homologues (TAL1) in the model plant Arabidopsis. Both TAC3 and TAL1 can negatively regulate flowering, and activate miR156 expression to delay the phase transition. Moreover, we found that HDA9 and its its homologues in Chinese fir, ClHDA9, can directly binding to the promoter region of MIR156A and ClMIR156A, respectively. Directly interaction with ClHDA9 and HDA9 are necessary for the transcriptional activation of TAC3 and TAL1 on miR156, respectively. TAC3 and TAL1 also involve in the chromatin remodeling, shown as up-regulated H3K27ac level within the promoter region of ClMIR156A and MIR156A. Together, this work shows that TAC3 and its homologues are a new group of transcriptional co-activator that involving in aging-dependent flowering signal pathway of both angiosperms and gymnosperms.
Z′
mediated right-handed neutrinos from meson decays at the FASER
Authors: Li Jiale , Liu Wei , Sun Hao
Published: February 2024

We investigate the pair production of right-handed neutrinos mediated by a Z′ mainly from the meson decays at the FASER detector of the HL-LHC. The Z′ can be the additional gauge boson in either the U(1)B−L or sterile ν-specific U(1)s model. Taking the gauge coupling or the kinetic mixing at the current limits, we analyze the sensitivity to the masses of the heavy neutrinos, MN, and active-sterile mixing, |VlN|2, of FASER2. In a background-free scenario, for the U(1)B−L case, FASER2 is able to probe |VlN|2≈10−8 when MN∼0.3  GeV, which is comparable to the current limits from the beam dump experiments. When comes to the U(1)s model, FASER2 can probe |VlN|2≈10−10, which is better than the current limits for at least one magnitude, in all three flavors. A proposed long-lived particle detector, FACET, is also studied, but no significant difference from FASER2 is derived.

Published by the American Physical Society
2024
Thermal behavior of effective
UA(1)
anomaly couplings in reflection of higher topological sectors
Authors: Fejős G. , Patkós A.
Published: February 2024

Thermal behavior of effective, chiral condensate-dependent UA(1) anomaly couplings is investigated using the functional renormalization group approach in the Nf=3 flavor meson model. We derive flow equations for anomaly couplings that arise from instantons of higher topological charge, dependent also on the chiral condensate. These flow equations are solved numerically for the |Q|=1, 2 topological sectors at finite temperature. Assuming that the anomaly couplings at the ultraviolet scale may also exhibit explicit temperature dependence, we calculate the thermal behavior of the effective potential. In accordance with our earlier study, [G. Fejos and A. Patkos, ], we find that for increasing temperatures, the anomalous breaking of chiral symmetry tends to strengthen toward the pseudocritical temperature (TC) of chiral symmetry breaking. It is revealed that below TC, around ∼10% of the UA(1) breaking arises from the |Q|=2 topological sector. Correspondingly, a detailed analysis on the thermal behavior of the mass spectrum is also presented.

Published by the American Physical Society
2024
Spectral and Krylov complexity in billiard systems
Authors: Camargo Hugo A. , Jahnke Viktor , Jeong Hyun-Sik , Kim Keun-Young , Nishida Mitsuhiro
Published: February 2024

In this work, we investigate spectral complexity and Krylov complexity in quantum billiard systems at finite temperature. We study both circle and stadium billiards as paradigmatic examples of integrable and nonintegrable quantum-mechanical systems, respectively. We show that the saturation value and timescale of spectral complexity may be used to probe the nonintegrability of the system since we find that when computed for the circle billiard, it saturates at a later timescale compared to the stadium billiards. This observation is verified for different temperatures. Furthermore, we study the Krylov complexity of the position operator and its associated Lanczos coefficients at finite temperature using the Wightman inner product. We find that the growth rate of the Lanczos coefficients saturates the conjectured universal bound at low temperatures. Additionally, we also find that even a subset of the Lanczos coefficients can potentially serve as an indicator of integrability, as they demonstrate erratic behavior specifically in the circle billiard case, in contrast to the stadium billiard. Finally, we also study Krylov entropy and verify its early-time logarithmic relation with Krylov complexity in both types of billiard systems.

Published by the American Physical Society
2024
Quantum Monte Carlo for gauge fields and matter without the fermion determinant
Authors: Banerjee Debasish , Huffman Emilie
Published: February 2024

Monte Carlo simulations of strongly interacting fermionic systems are plagued by the fermion sign problem, making the nonperturbative study of many interesting regimes of dense quantum matter, or of theories of odd numbers of fermion flavors, challenging. Moreover, typical fermion algorithms require the computation (or sampling) of the fermion determinant. We focus instead on the meron cluster algorithm, which can solve the fermion sign problem in a class of models without involving the determinant. We develop and benchmark new meron algorithms to simulate fermions coupled to Z2 and U(1) gauge fields in the presence of appropriate four-fermi interactions. Such algorithms can be used to uncover potential exotic properties of matter, particularly relevant for quantum simulator experiments. We demonstrate the emergence of the Gauss’ law at low temperatures for a U(1) model in (1+1)D.

Published by the American Physical Society
2024
Quantum limits of parameter estimation in long-baseline imaging
Authors: Sajjad Aqil , Grace Michael R. , Guha Saikat
Published: February 2024

Telescope systems with distributed apertures are a well-established approach for boosting resolution in astronomical imaging. However, theoretical limits on quantitative imaging precision, and the fundamentally best possible mode-sorting, beam-combining, and detection schemes to use with such arrays, remain largely unexplored. Using mathematical tools of the quantum and classical Crámer-Rao bounds, we perform analyses showing the fundamental origins of the enhancement provided by distributed imaging systems, over and above a single monolithic telescope, and consider the precision with which one can estimate any desired parameter embedded in a scene's incoherent radiation with a multi-aperture imaging system. We show how quantum-optimal measurements can be realized via beam-combination strategies of two classes: (1) , where light from different apertures is directed to a common focal plane, e.g., of a segmented-aperture telescope; and (2) , where light collected at each aperture, e.g., telescope sites of a long-baseline array, is routed to an optical interferometer. As an example, we show an explicit calculation of the quantum Fisher information (QFI) for estimating the angular separation between two-point emitters using two identical apertures separated by a baseline distance. We show that this QFI splits instructively into additive contributions from the single apertures and from the baseline. We quantify the relative benefits of intratelescope (e.g., spatial-mode) optical processing and intertelescope beam combination. We show how both receiver designs can be used to capture both sources of information and discuss how similar methods could be extended to more general imaging tasks. We discuss translating QFI-attaining measurements to explicit receiver designs, and the use of preshared entanglement to achieve the QFI when it is impractical to colocate and combine light collected by the apertures.

Published by the American Physical Society
2024
‘Young crystallographers’ rejuvenate crystallography in Germany
Authors: Meurer Florian , Möbs Jakob , Nentwich Melanie , Weigel Tina , Wöhrle Jan-Philipp
Published: February 2024

Since its founding in 2013, the Young Crystallographers (YC) have become one of the most active working groups not only within their parent organization, the German Crystallographic Society (DGK), but also among other young crystallographers' groups in Europe and the world. The aim of the YC is and always has been to support early-career researchers in the diverse fields of crystallography and the rejuvenation of the field on a national scale. Over the past decade, we have curated events, platforms, and educational content tailored to foster collaboration and knowledge transfer among young crystallographers. In this article, we introduce our group and show how this active and diverse community has shaped the rejuvenation of crystallography in Germany, strengthened by the support of our national society.