bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of human CD8+ T cell senescence on89Zr radiolabelling and homing properties
Authors: Bystrom Jonas , Carrascal-Miniño Amaia , Keeling George P , Pham Truc , Ketchley Conor Garrod- , Schroth Johannes , De Rosales Rafael T. M. , Terry Samantha YA , Henson Sian M. 
Published: February 2023

AbstractThe ability of CD8+ T cells to protect against infection and malignant transformation diminishes with age. Novel means to assess cellular functional deficitsin vivoare being made available such as total-body positron emission tomography (PET) and radiotracers with long half-lives. Here, we determined radiolabeled human CD8+ T cells isolated from young and old individuals with zirconium-89 (89Zr) and assessed their biological statusin vitroand distributionin vivo.MethodsFresh and cryopreserved CD8+ T cells from young and old individuals were labelled with varying activities of [89Zr]Zr-oxine and assessed for DNA damage and survival, subsequent toin vitroculture in the presence or absence of antioxidants.89Zr-labelled CD8+ T cells were injected intravenously in NSG mice and whole-body cell migration assessed using PET imaging.ResultsFresh and cryopreserved CD8+ T cells showed no difference in ability to be labelled with89Zr, radionuclide retention, or CD8+ T cell phenotype.89Zr induced partial cell death and DNA damage, which was no longer detectable visible after four days. The level of DNA repair observed in old samples was highly variable.89Zr efflux from cells, seenin vitro, did not occurin vivo. Longitudinal PET imaging indicated that CD8+ T cells from old individuals accumulated in tissues at a slower rate than those isolated from young individuals.ConclusionWe have established a strategy to label and track the biodistribution of cryopreserved CD8+T cells. Further study is required to understand differences in migratory behaviour of CD8+ T cells isolated from old and young individuals.
Understanding the Impact of Social Engagement Activities, Health Protocol Maintenance, and Social Interaction on Depression During Covid-19 Pandemic Among Older Americans
Authors: Ahmmad Roungu , Burns Paul A. , Alam Ashraful , Simino Jeannette , Yimer Wondwosen , Faruque Fazlay 
Published: February 2023

AbstractObjectivesDepression is a critical public health concern among older Americans. However, little is known about how older adults’ social engagement activities, health protocol maintenance, and social interaction (both physically and virtually) potentially contribute to their feelings of depression.MethodsData were collected from the Covid-19 supplement to the National Health and Aging Trend Study (NHATS) and core longitudinal follow-up study. A total of 3,181 Medicare-eligible older adults between June and December 2020 were examined how self-reported depression is related to social engagement activities, health protocols, social interaction with friends and family (F&F), and doctors using multiple logistic regression.ResultsThis study reveals that the lack of social engagement activities, such as birthday parties and long-term care visits significantly contributes to older adults’ depression (OR: 1.34, 90% CI: 1.07-1.68, p=0.012, and OR: 1.28, 90% CI: 1.01-1.65, p=0.053 respectively). Subsequently, health protocols compliance with washing hands and wearing masks in public places were more likely 2.36 times and 3.44 times higher symptoms of depression for the older adults than those who were not maintaining those protocols (OR: 2.36, 90% CI: 1.24-4.57, p=0.009, OR: 3.44, 90% CI: 1.97-6.17, p<0.001 respectively). Furthermore, the lack of virtual social interaction via phone and text message with F&F is significantly related to depression whereas email or video call are not significantly related to depression for older adults. During Covid-19 pandemic, in-person visits with doctors significantly reduced patients’ depression on the other hand email communication significantly increased. However other virtual interactions with doctors did not significantly associate with patients’ depression.ConclusionThe lack of social engagement, maintaining health protocols, and lacking virtual interactions over the phone significantly increase depression symptoms for older adults during the Covid-19 pandemic. Therefore, it would be beneficial to take initiative to engage older adults in a variety of social activities to make them feel more connected to their community. The older population should be contacted by phone during the Covid-19 pandemic with encouraging messages and informed of the importance of maintaining health protocols.
Functional anomaly mapping lateralizes temporal lobe epilepsy with high accuracy in individual patients
Authors: Gholipour Taha , DeMarco Andrew , You Xiaozhen , Englot Dario J , Turkeltaub Peter E , Koubeissi Mohamad Z , Gaillard William D. , Morgan Victoria L 
Published: February 2023

ObjectiveMesial temporal lobe epilepsy (mTLE) is associated with variable dysfunction beyond the temporal lobe. We used functional anomaly mapping (FAM), a multivariate machine learning approach to resting state fMRI analysis to measure subcortical and cortical functional aberrations in patients with mTLE. We also examined the value of individual FAM in lateralizing the hemisphere of seizure onset in mTLE patients. Methods: Patients and controls were selected from an existing imaging and clinical database. After standard preprocessing of resting state fMRI, time-series were extracted from 400 cortical and 32 subcortical regions of interest (ROIs) defined by atlases derived from functional brain organization. Group-level aberrations were measured by contrasting right (RTLE) and left (LTLE) patient groups to controls in a support vector regression models, and tested for statistical reliability using permutation analysis. Individualized functional anomaly maps (FAMs) were generated by contrasting individual patients to the control group. Half of patients were used for training a classification model, and the other half for estimating the accuracy to lateralize mTLE based on individual FAMs. Results: Thirty-two right and 14 left mTLE patients (33 with evidence of hippocampal sclerosis on MRI) and 94 controls were included. At group levels, cortical regions affiliated with limbic and somatomotor networks were prominent in distinguishing RTLE and LTLE from controls. At individual levels, most TLE patients had high anomaly in bilateral mesial temporal and medial parietooccipital default mode regions. A linear support vector machine trained on 50% of patients could accurately lateralize mTLE in remaining patients (median AUC =1.0 [range 0.97-1.0], median accuracy = 96.87% [85.71-100Significance: Functional anomaly mapping confirms widespread aberrations in function, and accurately lateralizes mTLE from resting state fMRI. Future studies will evaluate FAM as a non-invasive localization method in larger datasets, and explore possible correlations with clinical characteristics and disease course.
At the core of salinity: convergent and divergent transcriptome response pathways to neutral and alkaline salinity in natural populations ofArabidopsis thaliana
Authors: Almira-Casellas Maria , Busoms Sílvia , Pérez-Martín Laura , Escolà Glòria , López-Valiñas Álvaro , Garcia-Molina Antoni , Llugany Mercè , Poschenrieder Charlotte 
Published: February 2023

AbstractMore than 70% of land’s cultivated area is affected by alkaline salinity stress. As 98% of plants are glycophytes – unable to successfully reproduce under salinity – our previous research focused on comparative studies ofArabidopsis thalianademes with differential performance under neutral and alkaline salinity(neuSALandalkSAL) due to local adaptation processes. Here, an integrated analysis on leaf tissue was performed, including physiological indicators, nutritional status, endogenous phytohormonal concentration and transcriptome profiling, to further understand differences in molecular mechanisms underlyingneuSALandalkSALresponses. The results support thatalkSALis more detrimental to plant performance thanneuSALand indicate higher sensitivity toalkSALin demes locally adapted to coastal siliceous soils. A decreased internal Fe use efficiency in coastal demes underalkSALis proposed to be the driver of their enhanced sensitivity, and sequence variation at β-CA1 and α-CA1 locus is hypothesized to contribute to the imbalance of Fe homeostasis. Dissection on the down-regulated transcripts shared byneuSALandalkSALconfirmed enhanced inhibition of central features on primary and secondary metabolism in coastal individuals underalkSAL. The cell wall and vacuolar β-galactosidaseBGAL4was revealed as a candidate for conferring tolerance toneuSALby favoring stress-regulated cell wall rearrangement, but not toalkSAL, probably due to pH-restricted enzymatic activity. In addition, differential modulation of endogenous phytohormonal cues was reported among salinity types and demes, by which higher alteration of the auxinic, ethylene and jasmonic acid signaling pathways was exerted by alkSAL but sustained ABA biosynthesis was detected only in coastal plants under neuSAL. Weighted correlation network analysis (WGCNA) confirmed the involvement of the identified candidate genes in co-expression modules significantly correlating with favorable responses toneuSALandalkSAL. Overall, the present study provides useful insights into key targets for breeding improvement in alkaline saline soils.
FGF independent MEK1/2 signalling is essential for male fetal germline development in mice
Authors: Blücher Rheannon O. , Lim Rachel S. , Jarred Ellen G. , Ritchie Matthew E. , Western Patrick S. 
Published: February 2023

AbstractBackgroundGermline development provides the founding cells for spermatogenesis and oogenesis in males and females, respectively. Disrupted germline differentiation or compromised testis development can lead to subfertility or infertility and are strongly associated with testis cancer in humans. In mice, SRY and SOX9 induce expression of a range of genes, includingFgf9,that promote Sertoli cell differentiation and testis development. FGF9 is also thought to promote male germline differentiation but the pathway through which it signals is unknown. As FGFs signal through Mitogen-Activated Protein Kinases (MAPKs) in other tissues, we explored whether FGF9 regulates male germline development through MAPK by inhibiting either FGF or MEK1/2 signalling in fetal testis cultures from embryonic day (E)12.5, immediately after gonadal sex determination and testis cord formation, but prior to male germline commitment.ResultsInhibition of MEK1/2 disrupted mitotic arrest, dysregulated a broad range of male germline development genes and prevented the upregulation of key male germline markers DPPA4 and DNMT3L. In contrast, when FGF signalling was inhibited, the male germline specific transcriptional program and the expression of male germline markers DPPA4 and DNMT3L were unaffected, and germ cells entered mitotic arrest normally. While male germline development was not disrupted by FGF inhibition, some genes were commonly altered after 24h of FGF or MEK1/2 inhibition including genes involved in maintenance, germline stem cells, Nodal signalling, proliferation, and germline cancer.ConclusionsTogether, these data demonstrate a novel and essential role for MEK1/2 signalling in male germline differentiation, but a more limited role for FGF signalling. Our data strongly indicate that additional ligands act through MEK1/2 to promote male germline differentiation and highlight a need for further mechanistic understanding of male germline development.
Comparison of coil placement approaches targeting dorsolateral prefrontal cortex in depressed adolescents receiving repetitive transcranial magnetic stimulation: an electric field modeling study
Authors: Deng Zhi-De , Robins Pei L. , Dannhauer Moritz , Haugen Laura M. , Port John D. , Croarkin Paul E. 
Published: February 2023

AbstractBackgroundA promising treatment option for adolescents with treatment-resistant depression is high-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the left dorsolateral prefrontal cortex (L-DLPFC). Conventional coil placement strategies for rTMS in adults include the 5-cm rule, the Beam F3 method, and the magnetic resonance imaging (MRI) neuronavigation method. The purpose of this study was to compare the three targeting approaches to a computational E-field optimization coil placement method in depressed adolescents.MethodsTen consenting and assenting depressed adolescents (4 females, age: 15.9 ± 1.1) participated in an open-label rTMS treatment study. Participants were offered MRI-guided rTMS 5 times per week over 6–8 weeks. To compute the induced E-field, a head model was generated based on MRI images, and a figure-8 TMS coil (Neuronetics) was placed over the L-DLPFC using the four targeting approaches.ResultsResults show that there was a significant difference in the induced E-field at the L-DLPFC between the four targeting methods (χ2= 24.7,p <0.001).Post hocpairwise comparisons show that there was a significant difference between any two of the targeting methods (Holm adjustedp <0.05), with the 5-cm rule producing the weakest E-field (46.0 ± 17.4 V/m), followed by the F3 method (87.4 ± 35.4 V/m), followed by the MRI-guided (112.1 ± 14.6 V/m), and followed by the computationally optimized method (130.1 ± 18.1 V/m). The Bartlett test of homogeneity of variances show that there was a significant difference in sample variance between the groups (K2= 8.0,p <0.05), with F3 having the largest variance. In participants who completed the full course of treatment, the median E-field strength in the L-DLPFC was correlated with the change in depression severity (r=–0.77,p <0.05).ConclusionsThe E-field models revealed inadequacies of scalp-based targeting methods compared to MRI-guidance. Computational optimization may further enhance E-field dose delivery to the treatment target.
Autoantigen profiling reveals a shared post-COVID signature in fully recovered and Long COVID patients
Authors: Bodansky Aaron , Wang Chung-Yu , Saxena Aditi , Mitchell Anthea , Takahashi Saki , Anglin Khamal , Huang Beatrice , Hoh Rebecca , Lu Scott , Goldberg Sarah A. , Romero Justin , Tran Brandon , Kirtikar Raushun , Grebe Halle , So Matthew , Greenhouse Bryan , Durstenfeld Matthew S. , Hsue Priscilla Y. , Hellmuth Joanna , Kelly J. Daniel , Martin Jeffrey N. , Anderson Mark S. , Deeks Steven G. , Henrich Timothy J. , DeRisi Joseph L. , Peluso Michael J. 
Published: February 2023

ABSTRACTSome individuals do not return to baseline health following SARS-CoV-2 infection, leading to a condition known as Long COVID. The underlying pathophysiology of Long COVID remains unknown. Given that autoantibodies have been found to play a role in severity of COVID infection and certain other post-COVID sequelae, their potential role in Long COVID is important to investigate. Here we apply a well-established, unbiased, proteome-wide autoantibody detection technology (PhIP-Seq) to a robustly phenotyped cohort of 121 individuals with Long COVID, 64 individuals with prior COVID-19 who reported full recovery, and 57 pre-COVID controls. While a distinct autoreactive signature was detected which separates individuals with prior COVID infection from those never exposed to COVID, we did not detect patterns of autoreactivity that separate individuals with Long COVID relative to individuals fully recovered from SARS-CoV-2 infection. These data suggest that there are robust alterations in autoreactive antibody profiles due to infection; however, no association of autoreactive antibodies and Long COVID was apparent by this assay.
Patterns of testing in the extensive Danish national SARS-CoV-2 test set-up
Authors: Gram Mie Agermose , Steenhard Nina , Cohen Arieh Sierra , Vangsted Anne-Marie , Mølbak Kåre , Gorm Jensen Thøger , Hansen Christian Holm , Ethelberg Steen 
Published: February 2023

AbstractBackgroundThe Danish national SARS-CoV-2 mass test system was among the most ambitious worldwide. We describe its set-up and analyse differences in patterns of testing per demography and time period in relation to the three waves of SARS-CoV-2 transmission in Denmark.MethodsWe included all reported PCR- and rapid antigen-tests performed between 27 February 2020 and 10 March 2022 among all residents aged 2 years or above. Descriptive statistics and Poisson regression models were used to analyse characteristics of individuals tested for SARS-CoV-2 using a national cohort study design.ResultsA total of 63.7 million PCR-tests and 60.0 million antigen-tests were performed in the study period, testing 91.1% and 79.2% of the Danish population at least once by PCR or antigen, respectively. Female sex, younger age, Danish heritage and living in the capital area were all factors positively associated with the frequency of PCR-testing. The association between COVID-19 vaccination and PCR-testing changed from negative to positive over time.ConclusionWe provide details of the widely available, free-of-charge, national SARS-CoV-2 test system, which served to identify infected individuals, assist isolation of infectious individuals and contact tracing, and thereby mitigating the spread of SARS-CoV-2 in the Danish population. The test system was utilized by nearly the entire population at least once, and widely accepted across different demographic groups. However, demographic differences in the test uptake did exist and should be considered in order not to cause biases in studies related to SARS-CoV-2, e.g., studies of transmission and vaccine effectiveness.
Left bundle branch pacing with and without anodal capture: impact on ventricular activation pattern and acute hemodynamics
Authors: Ali Nadine , Saqi Khulat , Arnold Ahran D. , A.Miyazawa Alejandra , Keene Daniel , Chow Ji-Jian , Little Ian , Peters Nicholas S. , Kanagaratnam Prapa , Qureshi Norman , Ng Fu Siong , Linton Nick W. F , Lefroy David C. , Francis Darrel P. , Lim PB , Tanner Mark A. , Muthumala Amal , Shun-Shin Matthew J. , Cole Graham D. , Whinnett Zachary I. 
Published: February 2023

AbstractIntroductionLeft bundle branch pacing (LBBP) can deliver physiological left ventricular activation, but typically at the cost of delayed right ventricular (RV) activation. A proposed solution is to advance RV activation through anodal capture, but there is uncertainty regarding the mechanism by which early RV activation is achieved (capture of right bundle or RV myocardial capture) and it is not known whether this produces hemodynamic benefit.MethodsWe recruited patients with LBBP leads in whom anodal capture eliminated the terminal R wave in lead V1.Ventricular activation pattern, timing and high precision acute hemodynamic response were studied during LBBP with and without anodal capture.ResultsWe recruited 21 patients, mean age 67 years, 14 were males. We measured ECG timings and hemodynamics in all patients and in 15 we also performed non-invasive mapping. Ventricular epicardial propagation maps demonstrated that right ventricular septal myocardial capture, rather than right bundle capture, was the mechanism for earlier RV activation. With anodal capture, QRS duration was shorter (116 ± 12ms versus 129 ± 14ms, p < 0.01), and total ventricular activation time was shorter (83 ± 18ms versus 90 ± 15ms, p = 0.01). This required higher outputs (3.6 ± 1.9V versus 0.6 ± 0.2V, p <0.01) but did not provide additional hemodynamic benefit (mean difference −0.2 ± 3.8 mmHg compared to pacing without anodal capture, p = 0.2).ConclusionLeft bundle pacing with anodal capture advances right ventricular activation as a result of stimulation of the RV septal myocardium. However, this requires higher outputs and did not improve acute hemodynamics. Aiming for anodal capture may therefore not be necessary.
Soluble suppression of tumorigenicity-2 (sST2) predicts mortality and right heart failure in LVAD patients
Authors: Numan Lieke , Aarts Emmeke , Ramjankhan Faiz , Oerlemans Marish I.F. , van der Meer Manon G. , de Jonge Nicolaas , Oppelaar Anne-Marie , Kemperman Hans , Asselbergs Folkert W. , Van Laake Linda W. 
Published: February 2023

AbstractBackgroundSoluble suppression of tumorigenicity-2 (sST2) predicts mortality in heart failure patients. The predictive value of sST2 in left ventricular assist device (LVAD) patients remains unknown. Therefore, we studied the relationship between sST2 and outcome after LVAD implantation.MethodsPatients implanted between January 2015 and December 2022 were included. Survival of patients with normal and elevated pre-operative sST2 levels was compared using Kaplan-Meier analysis. The relationship between post-operative sST2, survival and right heart failure (RHF) was evaluated using a Joint Model (JM). Multivariate JM analysis adjusted for serially measured NT-proBNP was performed.ResultsThe median follow-up was 25 months, during which 1573 post-operative sST2 levels were measured in 199 patients, with a median of 29 ng/ml. Survival in patients with normal or elevated pre-operative sST2 levels (n=86) did not differ significantly (p=0.22). Time-dependent post-operative sST2 levels were significantly associated with mortality, with a hazard ratio (HR) of 1.20 (95% CI: 1.10-1.30, p<0.01) and a HR of 1.22 (95% CI: 1.07-1.39, p=0.01) for RHF, both per 10 unit sST2 increase. The sST2 instantaneous change was not predictive for survival or RHF (p=0.99, p=0.94 respectively). Multivariate JM analysis showed a significant relationship between sST2 with mortality adjusted for NT-proBNP with HR 1.19 (95% CI: 1.00-1.42, p=0.05), while the HR of RHF was not significant (1.22, 95% CI: 0.94-1.59, p=0.14), both per 10 unit sST2 increase.ConclusionTime-dependent post-operative sST2 predicts all-cause mortality after LVAD implantation independently of NT-proBNP. Future research is warranted into possible target interventions and the optimal monitoring frequency.
Loss of Y is associated with multi-omic changes in immune cells from Alzheimer’s disease patients
Authors: Jąkalski Marcin , Rychlicka-Buniowska Edyta , Davies Hanna , Sarkisyan Daniil , Siedlar Maciej , Baran Jaroslaw , Węglarczyk Kazimierz , Jaszczynski Janusz , Ryś Janusz , Gedraitis Vilmantas , Klich-Rączka Alicja , Kilander Lena , Ingelsson Martin , Dumanski Jan P. , Mieczkowski Jakub 
Published: February 2023

ABSTRACTAlzheimer’s disease (AD) is a common and increasing societal problem due to the extending human lifespan. In males, loss of Y (LOY) in leukocytes is more prevalent in AD patients. We studied DNA methylation, gene expression and other epigenetic changes in monocytes and granulocytes with and without LOY from male AD patients and controls. New candidate genes were identified and numerous genes already implicated in AD pathogenesis were confirmed. We show that multi-omics of leukocytes can define AD candidate genes and we strengthen the role of LOY in disease development. The LOY-associated differences in DNA methylation levels were predominantly observed in regulatory regions, and supported by expression analysis showing down-regulation of immune genes. The single-cell transcriptomics highlighted that the AD patient-specific immune activation dominates over LOY-specific activation. Our findings agree with the hypothesis that age-related dysfunction of immune cells contribute to AD and that LOY is reflected by higher-level epigenetic changes with an AD-specific pattern.