bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surrogate Perception of Disability after Hospitalization for Traumatic Brain Injury
Authors: Maiga Amelia W , Cook Madison , Nordness Mina F , Gao Yue , Rakhit Shayan , Rivera Erika L , Harrell Frank E , Sharp Kenneth W , Patel Mayur B 
Published: January 2024

BACKGROUND:
The Glasgow Outcome Scale Extended (GOSE) is a measure of recovery after traumatic brain injury (TBI). Public surveys rate some GOSE states as worse than death. Direct family experience caring for patients with TBI may impact views of post-TBI disability.

STUDY DESIGN:
We conducted a national cross-sectional computer-adaptive survey of surrogates of TBI dependents incurring injury more than 1 year earlier. Using a standard gamble approach in randomized order, surrogates evaluated preferences for post-TBI GOSE states from GOSE 2 (bedridden, unaware) to GOSE 8 (good recovery). We calculated median (interquartile range [IQR]) health utilities for each post-TBI state, ranging from −1 to 1, with 0 as reference (death = GOSE 1), and assessed sociodemographic associations using proportional odds logistic regression modeling.

RESULTS:
Of 515 eligible surrogates, 298 (58%) completed scenarios. Surrogates were median aged 46 (IQR 35 to 60), 54% married, with Santa Clara strength of faith 14 (10 to 18). TBI dependents had a median GOSE5 (3 to 7). Median (IQR) health utility ratings for GOSE 2, GOSE 3, and GOSE 4 were −0.06 (−0.50 to −0.01), −0.01 (−0.30 to 0.45), and 0.30 (−0.01 to 0.80), rated worse than death by 91%, 65%, and 40%, respectively. Surrogates rated GOSE 4 (daily partial help) worse than the general population. Married surrogates rated GOSE 4 higher (p < 0.01). Higher strength of faith was associated with higher utility scores across GOSE states (p = 0.034).

CONCLUSIONS:
In this index study of surrogate perceptions about disability after TBI, poor neurologic outcomes—vegetative, needing all-day or partial daily assistance—were perceived as worse than death by at least 1 in 3 surrogates. Surrogate perceptions differed from the unexposed public. Long-term perceptions about post-TBI disability may inform earlier, tailored shared decision-making after neurotrauma.
Gating of Memory to Behavior by the Locus Coeruleus
Authors: Wang Tianyu , Zhang Xinyang , Duan Haoyu , Xia Dan , Li Tianxiang , Yan Rongzhen , Zhan Yang , Li Yulong , Gao Wen-Jun , Zhou Qiang 
Published: January 2024

AbstractAn essential function of memory is to guide behavior for survival and adaptation. While considerable knowledge has been accumulated on memory formation, much less is understood about how retrieved memories direct behavior/action. In the auditory Pavolovian threat conditioning paradigm, retrieval of conditioned threat memory activates dorsomedial prefrontal (dmPFC) neurons exhibiting transient responses (T-neurons), which activate both dmPFC neurons exhibiting sustained responses (S-neurons) and locus coeruleus (LC) neurons. Auditory inputs to S-neurons enable the conversion from transient to sustained responses so that the freezing durations match those of the auditory cues. Activation of LC neurons is required for the conversion by enhancing S-neuron responses, which, interestingly, opens a short time window during which non-conditioned cues also lead to freezing. The transition from memory to behavior thus hinges on the integration of retrieved memory, sensory inputs, and emotional/body state cues to generate a selective, adequate, and finely tuned behavior.Significance statementThis study provides new insights into the neural circuitry and mechanisms of how retrieved memories direct the execution of behavior in response to conditioned threatening stimuli. It reveals how different neuron types in the dmPFC interact with LC neurons to determine and modulate the duration and intensity of defensive responses. It also shows that activation of LC neurons can induce the generalization of freezing to non-threatening cues, which may have implications for understanding anxiety disorders. This study contributes to the field of neuroscience by advancing the understanding of memory-behavior conversion and role of the dmPFC and LC in conditioned threat/fear behavior.
Reduced Oxygen Extraction Fraction in Deep Cerebral Veins Associated with Cognitive Impairment in Multiple Sclerosis
Authors: Sawan Hasan , Li Chenyang , Buch Sagar , Bernitsas Evanthia , Haacke E. Mark , Ge Yulin , Chen Yongsheng 
Published: January 2024

ABSTRACTStudying the relationship between cerebral oxygen utilization and cognitive impairment is essential to understanding neuronal functional changes in the disease progression of multiple sclerosis (MS). This study explores the potential of using venous susceptibility in internal cerebral veins (ICVs) as an imaging biomarker for cognitive impairment in relapsing-remitting MS (RRMS) patients. Quantitative susceptibility mapping derived from fully flow-compensated MRI phase data was employed to directly measure venous blood oxygen saturation levels (SvO2) in the ICVs. Results revealed a significant reduction in the susceptibility of ICVs (212.4 ± 30.8 ppb vs 239.4 ± 25.9 ppb) and a significant increase of SvO2(74.5 ± 1.89 % vs 72.4 ± 2.23 %) in patients with RRMS compared with age- and sex-matched healthy controls. Both the susceptibility of ICVs (r= 0.646,p= 0.004) and the SvO2(r= −0.603,p= 0.008) exhibited a strong correlation with cognitive decline in these patients assessed by the Paced Auditory Serial Addition Test, while no significant correlation was observed with clinical disability measured by the Expanded Disability Status Scale. The findings suggest that venous susceptibility in ICVs has the potential to serve as a specific indicator of oxygen metabolism and cognitive function in RRMS.
Associations between Sympathetic Nerve Activity and Ischemia in Takotsubo Syndrome and Stable Ischemic Heart Disease
Authors: Borle Sanjana , Liu Xiao , Kote Anxhela , Rosenberg Carine , Reaso Jewel , Chen Peng-Sheng , Bairey Merz C. Noel , Wei Janet 
Published: January 2024

AbstractBackgroundPatients with stable ischemic heart disease (IHD) frequently experience ambulatory myocardial ischemia. Takotsubo Syndrome (TTS) often mimics IHD and is associated with heightened sympathetic activity. We hypothesized that skin sympathetic nerve activity (SKNA) differs between participants with prior TTS, stable IHD, and reference controls and that SKNA increases relative to electrocardiographic (ECG) evidence of ischemia.MethodsSimultaneous recordings of SKNA and ECG (neuECG) measured ST height and average SKNA (aSKNA) in ambulatory participants with a history of TTS (n=6), stable IHD (n=7), and reference controls (n=19). Ambulatory ischemia was defined as ischemic ST segment depression ≥0.5 mm. SKNA burst frequency, duration, amplitude, and total area above the threshold were calculated during ischemic and non-ischemic episodes.ResultsBaseline aSKNA was similar between TTS, IHD, and reference controls (0.980± 0.061 µV vs 0.916±0.050 µV vs 1.098±0.291 µV respectively, p=0.06). Ischemic episodes (n=15) were identified in 2 TTS and 4 IHD participants, while reference controls had none. Among the TTS and IHD groups, ischemic ST depression was associated with increased heart rate and elevated aSKNA from baseline. An analysis of SKNA burst patterns at similar heart rates revealed that SKNA total burst area was significantly higher during ischemic episodes than non-ischemic episodes (0.301±0.380 µV.s and 0.165±0.205 µV.s, p=0.023) in both the TTS and IHD participants.ConclusionsCompared with heart rate-matched non-ischemic episodes, ischemic episodes were associated with larger SKNA burst areas in the TTS and IHD groups. The neuECG may be a useful tool in studying the pathophysiology of sympathetic nervous system-related ischemia.Clinical PerspectiveAmbulatory monitoring with neuECG can assess sympathetic skin nerve activity (SKNA) and electrocardiography simultaneously.We found that ischemic episodes are present not only in patients with stable ischemic heart disease (SIHD) but also those with a history of Takotsubo Syndrome.SKNA burst activity was greater during ischemic episodes than nonischemic episodes in patients with SIHD and history of Takotsubo Syndrome.NeuECG may be a noninvasive tool in studying mechanisms of sympathetic nervous system-related ischemia.
NGN3 oscillatory expression controls the timing of human pancreatic endocrine differentiation
Authors: Miller Anzy , Biga Veronica , Rowntree Andrew , Chhatriwala Mariya , Woods Florence , Marinopoulou Elli , Kamath Anoushka , Vallier Ludovic , Papalopulu Nancy 
Published: January 2024

SummaryUnderstanding protein expression dynamics is crucial for the mechanistic understanding of cell differentiation. We investigate the dynamics of NGN3, a transcription factor critical for pancreatic endocrine development, including their function and decoding mechanisms. A knock-in endogenous reporter shows that the expression of NGN3 protein oscillates with a 13-hour periodicity in human iPS-derived endocrine progenitors and is switched off as cells differentiate to β-like and α-like cells. Increasing the stability of NGN3 protein results in one broad peak of expression instead of oscillations, with a larger peak to trough fold-change. This leads to precocious endocrine differentiation to both β-like and α-like cells and precocious expression of key NGN3 target genes. Single-cell analysis of dynamics, mathematical modelling and bioinformatics suggest that decoding of NGN3 oscillations occurs by fold-change detection via an incoherent feedforward motif that explains both normal and precocious differentiation. Our findings suggest that oscillatory NGN3 dynamics control the timing of differentiation, but not fate specification.
CD14 Blockade Does Not Improve Outcomes of Deep Vein Thrombosis Following Inferior Vena Cava Stenosis in Mice
Authors: Pandey Nilesh , Kaur Harpreet , Chandaluri Lakshmi , Anand Sumit Kumar , Chokhawala Himanshu , Magdy Tarek , Stokes Karen Y , Orr A Wayne , Rom Oren , Dhanesha Nirav 
Published: January 2024

ABSTRACTBackgroundNeutrophil-mediated persistent inflammation and neutrophil extracellular trap formation (NETosis) promote deep vein thrombosis (DVT). CD14, a co-receptor for toll-like receptor 4 (TLR4), is actively synthesized by neutrophils, and the CD14/TLR4 signaling pathway has been implicated in proinflammatory cytokine overproduction and several aspects of thromboinflammation. The role of CD14 in the pathogenesis of DVT remains unclear.ObjectiveTo determine whether CD14 blockade improves DVT outcomes.MethodsBulk RNA sequencing and proteomic analyses were performed using isolated neutrophils following inferior vena cava (IVC) stenosis in mice. DVT outcomes (IVC thrombus weight and length, thrombosis incidence, neutrophil recruitment, and NETosis) were evaluated following IVC stenosis in mice treated with a specific anti-CD14 antibody, 4C1, or control antibody.ResultsMice with IVC stenosis exhibited increased plasma levels of granulocyte colony-stimulating factor (G-CSF) along with a higher neutrophil-to-lymphocyte ratio and increased plasma levels of cell-free DNA, elastase, and myeloperoxidase. Quantitative measurement of total neutrophil mRNA and protein expression revealed distinct profiles in mice with IVC stenosis compared to mice with sham surgery. Neutrophils of mice with IVC stenosis exhibited increased inflammatory transcriptional and proteomic responses, along with increased expression of CD14. Treatment with a specific anti-CD14 antibody, 4C1, did not result in any significant changes in the IVC thrombus weight, thrombosis incidence, or neutrophil recruitment to the thrombus.ConclusionThe results of the current study are important for understanding the role of CD14 in the regulation of DVT and suggest that CD14 lacks an essential role in the pathogenesis of DVT following IVC stenosis.
Increased chromatin accessibility mediated by nuclear factor I drives transition to androgen receptor splice variant dependence in castration-resistant prostate cancer
Authors: Poluben Larysa , Nouri Mannan , Liang Jiaqian , Varkaris Andreas , Ersoy-Fazlioglu Betul , Voznesensky Olga , Lee Irene I. , Qiu Xintao , Cato Laura , Seo Ji-Heui , Freedman Matthew L. , Sowalsky Adam G. , Lack Nathan A. , Corey Eva , Nelson Peter S. , Brown Myles , Long Henry W. , Russo Joshua W. , Balk Steven P. 
Published: January 2024

ABSTRACTAndrogen receptor (AR) splice variants, of which ARv7 is the most common, are increased in prostate cancer (PC) that develops resistance to androgen signaling inhibitor drugs, but the extent to which these variants drive AR activity, and whether they have novel functions or dependencies, remain to be determined. We generated a subline of VCaP PC cells (VCaP16) that is resistant to the AR inhibitor enzalutamide (ENZ) and found that AR activity was independent of the full-length AR (ARfl), despite its continued high-level expression, and was instead driven by ARv7. The ARv7 cistrome and transcriptome in VCaP16 cells mirrored that of the ARfl in VCaP cells, although ARv7 chromatin binding was weaker, and strong ARv7 binding sites correlated with higher affinity ARfl binding sites across multiple models and clinical samples. Notably, although ARv7 expression in VCaP cells increased rapidly in response to ENZ, there was a long lag before it gained chromatin binding and transcriptional activity. This lag was associated with an increase in chromatin accessibility, with the AR and nuclear factor I (NFI) motifs being most enriched at these more accessible sites. Moreover, the transcriptional effects of combined NFIB and NFIX knockdown versus ARv7 knockdown were highly correlated. These findings indicate that ARv7 can drive the AR program, but that its activity is dependent on adaptations that increase chromatin accessibility to enhance its intrinsically weak chromatin binding.
Generative artificial intelligence performs rudimentary structural biology modeling
Authors: Ille Alexander M. , Markosian Christopher , Burley Stephen K. , Mathews Michael B. , Pasqualini Renata , Arap Wadih 
Published: January 2024

AbstractNatural language-based generative artificial intelligence (AI) has become increasingly prevalent in scientific research. Intriguingly, capabilities of generative pre-trained transformer (GPT) language models beyond the scope of natural language tasks have recently been identified. Here we explored how GPT-4 might be able to perform rudimentary structural biology modeling. We prompted GPT-4 to model 3D structures for the 20 standard amino acids and an α-helical polypeptide chain, with the latter incorporating Wolfram mathematical computation. We also used GPT-4 to perform structural interaction analysis between nirmatrelvir and its target, the SARS-CoV-2 main protease. Geometric parameters of the generated structures typically approximated close to experimental references. However, modeling was sporadically error-prone and molecular complexity was not well tolerated. Interaction analysis further revealed the ability of GPT-4 to identify specific amino acid residues involved in ligand binding along with corresponding bond distances. Despite current limitations, we show the capacity of natural language generative AI to perform basic structural biology modeling and interaction analysis with atomic-scale accuracy.
Genomic surveillance of SARS-CoV-2 and emergence of XBB.1.16 variant in Rajasthan
Authors: Sharma Pratibha , Gautam Swati , Sharma Abhaya , Parsoya Dinesh , Deeba Farah , Pal Nita , Singh Ruchi , Sharma Himanshu , Bhomia Neha , Sharma Ravi P. , Potdar Varsha , Malhotra Bharti 
Published: January 2024

AbstractBackground & objectivesGenomic surveillance of positive SARS-CoV-2 samples is important to monitor the genetic changes occurring in virus, this was enhanced after the WHO designation of XBB.1.16 as a variant under monitoring in March 2023. From 5thFebruary till 6thMay 2023 all positive SARS-CoV-2 samples were monitored for genetic changes.MethodsA total of 1757 samples having Ct value <25 (for E and ORF gene) from different districts of Rajasthan were processed for Next Generation sequencing (NGS). The FASTA files obtained on sequencing were used for lineage determination using Nextclade and phylogenetic tree construction.Results and discussionSequencing and lineage identification was done in 1624 samples. XBB.1.16 was the predominant lineage in 1413(87.0%) cases while rest was other XBB (207, 12.74%) and other lineages (4, 0.2%). Of the 1413 XBB.1.16 cases, 57.47% were males and 42.53% were females. Majority (66.53%) belonged to 19-59 year age. 84.15% of XBB.1.16 cases were infected for the first time. Hospitalization was required in only 2.2% cases and death was reported in 5 (0.35%) patients. Most of the cases were symptomatic and the commonest symptoms were fever, cough and rhinorrhoea. Co-morbidities were present in 414 (29.3%) cases. Enhanced genomic surveillance helped to rapidly identify the spread of XBB variant in Rajasthan. This in turn helped to take control measures to prevent spread of virus and estimate public health risks of the new variant relative to the previously circulating lineages. XBB variant was found to spread rapidly but produced milder disease.
A Multilevel Intervention to Reduce Chronic Disease Risk in Socioeconomically Disadvantaged Unemployed Populations: TheNorth Carolina Works 4 Health (NCW4H)Clinical Trial Protocol
Authors: Kneipp Shawn M. 
Published: January 2024

AbstractBackgroundThe overall goal of the North Carolina Works for Health (NCW4H) study is to adapt and test the effectiveness of a multilevel intervention to reduce chronic disease risk in socioeconomically disadvantaged, unemployed (SEDU) populations who rely on publicly-funded job placement programs to secure employment. Studies have shown an unemployment episode increases in psychological distress, health-compromising coping behavior, blood pressure, and weight gain – all of which increase chronic disease risk.MethodsA randomized, 2 x 2 factorial design will test an individual level (IL) and employer level (EL) intervention, and their joint effects, in SEDU adults receiving job placement services through publicly-funded programs. Interventions consist of a chronic disease prevention program adapted from the Diabetes Prevention Program at the IL, and an implicit bias-based supervisor support program for newly-hired SEDU adults at the EL. We will enroll 600 SEDU adults 18 to 64 years of age who have either received public assistance benefits in the prior two yearsorhave <4-year college degree, used publicly-funded job placement services during the most recent unemployment episode, and are not receiving disability income, not pregnant, and fluent in English; and 80-200 supervisors of our SEDU enrolled participants when hired by an employer. Primary outcomes include psychological distress, blood pressure, and weight gain, and will be collected at baseline and 3, 6, and 12 months post-enrollment. Secondary outcomes related to coping, health behavior, workplace support, and employment will also be collected. Main effects of the IL and EL interventions, and IL x EL interactions, will be analyzed using generalized multivariate models accounting for clustering effects.DiscussionThis multilevel intervention is novel in that it is designed to mitigate chronic disease risk during an unemployment episode, and includes an intervention at a level at the employer level, where social determinants of health operate. Despite the design challenges that multilevel intervention trials such as the NCW4H study present, they are needed to meaningfully address health inequities in the U.S. Findings from this study are expected to inform how approaches that incorporate public health and employment sectors could reduce chronic disease among socioeconomically disadvantaged populations.Ethics and disseminationThe trial is ongoing and has been approved by the University of North Carolina at Chapel Hill Institutional Review Board. Trial results will be published in a scientific journal and presented at scientific conferences.Trial registration numberNCT04815278, ClinicalTrials.gov
Binding domain mutations provide insight into CTCF’s relationship with chromatin and its contribution to gene regulation
Authors: Do Catherine , Jiang Guimei , Cova Giulia , Katsifis Christos C. , Narducci Domenic N. , Sakellaropoulos Theodore , Vidal Raphael , Lhoumaud Priscillia , Tsirigos Aristotelis , Regis Faye Fara D. , Kakabadze Nata , Nora Elphege P , Noyes Marcus , Hansen Anders S. , Skok Jane A 
Published: January 2024

SummaryHere we used a series of CTCF mutations to explore CTCF’s relationship with chromatin and its contribution to gene regulation. CTCF’s impact depends on the genomic context of bound sites and the unique binding properties of WT and mutant CTCF proteins. Specifically, CTCF’s signal strength is linked to changes in accessibility, and the ability to block cohesin is linked to its binding stability. Multivariate modelling reveals that both CTCF and accessibility contribute independently to cohesin binding and insulation, however CTCF signal strength has a stronger effect. CTCF and chromatin have a bidirectional relationship such that at CTCF sites, accessibility is reduced in a cohesin-dependent, mutant specific fashion. In addition, each mutant alters TF binding and accessibility in an indirect manner, changes which impart the most influence on rewiring transcriptional networks and the cell’s ability to differentiate. Collectively, the mutant perturbations provide a rich resource for determining CTCF’s site-specific effects.
A bibliometric analysis of trends in the relationship between innovation and food
Authors: Dzhunushalieva Gulnara Dzhenishevna , Teuber Ramona 
Published: January 2024

PurposeFood-related innovations might contribute to a qualitative leap in the transition to sustainable food systems. In this article, the authors map the existing literature on food and innovation in order to identify and systematise major research streams and relate them to current discussions on sustainability. The authors rely on a broad definition of innovation covering specific technological innovations as well as social, environmental and system innovations.Design/methodology/approachThe authors analysed the relationship between innovation and food through bibliometric and content analysis, augmented with visualisation based on data (N = 7,987) extracted from the Web of Science. The published volume, research areas and influential journals were investigated using descriptive analyses.FindingsThis review categorises the literature on innovation and food into six main clusters, showing that most of the studies are carried out at the macro-level related to the global sustainable food systems. Network visualisation allowed them to distribute recent keywords associated with innovation across the agri-food value chain. Moreover, the authors identified environmental, social and economic pillars of innovation, which not only relate to sustainability but also are associated with open innovation as well as social innovation and eco-innovation.Originality/valueThis bibliometric analysis is amongst the first to examine the holistic knowledge structure surrounding a triple concept of innovation, food and sustainability. In addition, the study identifies research gaps and indicates new research directions, which add further value.