bluuebunny/crossref_metadata_2025_split huggingface dataset:
GEO Data Sets Analysis On Mechanism of Action of IFNβ-1a Treatment in Multiple Sclerosis
Authors: Ho Adam 
Published: March 2023

AbstractMultiple Sclerosis (MS) is an autoimmune disease that affects millions of people worldwide and causes symptoms such as dysarthria, ataxia, and nystagmus. MS is known to be characterized by an autoimmune attack by the immune system on the myelin sheath of neurons, causing inflammation and scarring (sclerosis). In the status quo, MS is treated or alleviated by disease-modifying therapies, including beta interferons (IFNβ) and monoclonal antibodies. Yet, the mechanism of action (MOA) of IFNβ is not fully understood, and only a limited proportion of patients respond to IFNβ treatment. Mononuclear cells from therapy-naïve MS patients, IFN-β-1a-treated MS patients after 12 months from three databases on GEO are analysed to examine RNA changes that characterize both the disease and its treatment. 28 differentially expressed genes (DEGs) are identified in all three of the databases and passed the cut-off criteria. Using the 28 DEGs, we performed DAVID and PANTHER analysis, revealing that the biological process “immune response”, “defence against virus”, and “regulation of viral genome replication” are enriched. A protein interaction network for the DEGs was constructed and a protein module was identified and analysed with PANTHER, revealing “interleukin-27-mediated signalling pathway”, “regulation of ribonuclease activity”, “regulation of type III interferon production”, “cellular response to exogenous double-stranded RNA (dsRNA)”, and “ISG15-protein conjugation are enriched for >100 folds. Cytoscape analysis further identified the hub genes IFI44L, IFI44, and STAT1 and they may be important mediators in the therapeutic effect of IFNβ treatment and warrant further study. Overall, the findings of the present study provide insights into the MOA of IFNβ-1a and provide greater confidence on which genes are differentially expressed in MS before and after IFNβ-1a treatment. The results also are additional evidence for the role of viral infection in MS, a topic that is gaining interest in the MS research community.
Uptake of intramuscular vitamin K administration after birth and maternal and infant demographic variables: a national cohort study
Authors: Brunton S , Fenton L , Hardelid P , Williams TC 
Published: March 2023

AbstractA long-acting monoclonal antibody against Respiratory Syncytial Virus (RSV), given as a one-off injection shortly after birth, is likely to be introduced soon. We hypothesised that carer acceptance of intra-muscular (IM) vitamin K, another injection given shortly after birth, might serve as a proxy indicator of likely acceptance of any such anti-RSV intervention, given previous associations described between IM vitamin K acceptance and subsequent non-immunisation. Using a national dataset of all postnatal health visitor visits in Scotland from 2018-2021 we explored demographic variables associated with non-acceptance of IM vitamin after birth. We found that in the time period 2019-2021 over 95.5% of carers were documented as consenting to this intervention, with only 1.1% requesting oral vitamin K and 0.9% refusing vitamin K altogether. Infant ethnicity, use of English as a first language at home, socio-economic position and maternal age were not associated with reduced uptake of IM vitamin K. We therefore did not identify any groups that might require increased engagement prior to the roll-out of a long-acting monoclonal antibody for RSV.
Differential effects of frailty on biventricular function and prognosis analysis in senile patients
Authors: Jing Jiang , Baojun Yang , Zhao Zhiying , Dili Xie , Yunhe Zhang , Rong Yu , Jing Jin 
Published: March 2023

AbstractObjectiveTo investigate the differential effects of frailty on biventricular function in senile patients and analyse the prognosis of different combinations of clinical status.Methods and ResultsPatients aged ≥80 years with at least one basic disease causing heart failure were included and divided into three groups according to frailty score. Basic data, ultrasound data, and follow-up data were collected and analyses of differences between groups and survival were performed. The proportion of patients with right heart failure in the frailty group was significantly higher than that in the others. A total of 33 (15.1%) patients died within a year, 162 (74%) were readmitted within 1 year, and 84 (38.4%) were admitted for heart failure within 1 year. The frailty group with right heart failure had the highest rate of all cause and heart failure-related readmission. Frailty significantly increased the risk of 1-year all-cause mortality, all-cause readmission, and heart failure-related readmission. Right heart failure significantly increased the 1-year all-cause readmission and heart failure-related readmission rates. After adjusting for the interaction of factors, only frailty had a significant effect on the three prognostic events.ConclusionsRight heart failure is more likely to be associated with frailty in senile patients. One-year all-cause mortality, all-cause readmission, and heart failure-related readmission rates were significantly increased in frail patients with right heart failure.Frailty was a significant predictor of all-cause death, all-cause readmission, and heart failure-related readmission.
Ventricular Dyssynchrony Late after the Fontan Operation is Associated with Decreased Survival and the Presence of Arrhythmias
Authors: Gearhart Addison , Bassi Sunakshi , Rathod Rahul H. , Beroukhim Rebecca S. , Lipsitz Stuart , Gold Maxwell P. , Harrild David M. , Dionne Audrey , Ghelani Sunil J. 
Published: March 2023

AbstractBackgroundVentricular dyssynchrony and its relationship to clinical outcomes is not well characterized in patients following Fontan palliation.MethodsSingle-center retrospective analysis of cardiac magnetic resonance (CMR) imaging of patients with a Fontan circulation and age-matched healthy comparison cohort as controls. Feature tracking was performed on all slices of a ventricular short-axis cine stack. Circumferential and radial strain, strain rate, and displacement were measured; and multiple dyssynchrony metrics were calculated based on timing of these measurements (including standard deviation of time-to-peak, maximum opposing wall delay, and maximum base-to-apex delay). Primary endpoint was a composite measure including time to death or heart transplant listing (D/HTx); secondary outcomes were the presence of atrial or ventricular arrhythmias.ResultsA total of 503 cases (15y; IQR 10, 21) and 42 controls (16y; IQR 11, 20) were analyzed. Compared to controls, Fontan patients had increased dyssynchrony metrics, longer QRS duration, larger ventricular volumes, and worse systolic function. Dyssynchrony metrics were higher in patients with right ventricular (RV) or mixed morphology compared to those with LV morphology. At median follow-up of 4.3 years, 11% had D/HTx, 7% ventricular arrhythmia, and 38% atrial arrhythmia. Multiple risk factors for D/HTx were identified, including RV morphology, ventricular dilation, dysfunction, QRS prolongation, and dyssynchrony. Ventricular dilation and RV morphology were independently associated with D/HTx; ventricular dilation and global circumferential strain were independently associated with ventricular and atrial arrhythmias.ConclusionsMechanical dyssynchrony is highly prevalent in functional single ventricles palliated to the Fontan circulation and is more pronounced in hearts with RV or mixed ventricular morphology compared to those with LV morphology. Dyssynchrony is associated with death or need for heart transplantation and cardiac arrhythmias. These data add to the growing understanding regarding factors that can be used to risk-stratify patients with the Fontan circulation.
Elevated symptoms of depression and anxiety among family members of critically ill COVID-19 patients - An observational study of five cohorts across four countries
Authors: Lovik Anikó , González-Hijón Juan , Hoffart Asle , Fawns-Ritchie Chloe , Magnúsdóttir Ingibjörg , Lu Li , Unnarsdóttir Anna Bára , Kähler Anna K. , Campbell Archie , Hauksdóttir Arna , Chourpiliadis Charilaos , McCartney Daniel L. , Thordardóttir Edda Björk , Joyce Emily E. , Frans Emma M. , Jakobsdóttir Jóhanna , Trogstad Lill , Andreassen Ole A. , Magnus Per , Johnson Sverre Urnes , Sullivan Patrick F. , Aspelund Thor , Porteous David J. , Ask Helga , Ebrahimi Omid V. , Valdimarsdóttir Unnur Anna , Fang Fang 
Published: March 2023

AbstractBackgroundLittle is known regarding the mental health impact of having a significant person (family member and/or close friend) with COVID-19 of different severity.MethodsThe study included five prospective cohorts from four countries (Iceland, Norway, Sweden, and the UK) with self-reported data on COVID-19 and symptoms of depression and anxiety during March 2020-March 2022. We calculated the prevalence ratio (PR) of depression and anxiety in relation to having a significant person with COVID-19 and performed a longitudinal analysis in the Swedish cohort to describe the temporal patterns of the results.Results162,237 and 168,783 individuals were included in the analysis of depression and anxiety, respectively, of whom 24,718 and 27,003 reported a significant person with COVID-19. Overall, the PR was 1.07 (95% CI: 1.05-1.10) for depression and 1.08 (95% CI: 1.03-1.13) for anxiety among significant others of COVID-19 patients. The respective PRs for depression and anxiety were 1.04 (95% CI: 1.01-1.07) and 1.03 (95% CI: 0.98-1.07) if the significant person was never hospitalized, 1.15 (95% CI: 1.08-1.23) and 1.24 (95% CI: 1.14-1.34) if the patient was hospitalized, 1.42 (95% CI: 1.27-1.57) and 1.45 (95% CI: 1.31-1.60) if admitted to the ICU, and 1.34 (95% CI: 1.22-1.46) and 1.36 (95% CI: 1.22-1.51) if the significant person died. Individuals of hospitalized, ICU admitted, or deceased patients showed higher prevalence of depression and anxiety during the entire 12 months after the COVID-19 diagnosis of the significant person.ConclusionsClose friends and family members of critically ill COVID-19 patients show elevated prevalence of depression and anxiety throughout the first year after the diagnosis.
CBD lengthens sleep, shortens ripples and leads to intact simple but worse cumulative memory
Authors: Samanta Anumita , Aleman-Zapata Adrian , Agarwal Kopal , Özsezer Pelin , Alonso Alejandra , van der Meij Jacqueline , Rayan Abdelrahman , Navarro-Lobato Irene , Genzel Lisa 
Published: March 2023

AbstractCannabidiol (CBD) is on the rise as over-the-counter medication to treat sleep disturbances, anxiety, pain and epilepsy due to its action on the excitatory/inhibitory balance in the brain. However, it remains unclear if CBD also leads to adverse effects via changes of sleep macro- and microarchitecture. To investigate the effect of CBD on sleep and sleep-related memory consolidation, we performed two experiments using the Object Space Task testing both simple and cumulative memory in rats. We show that oral CBD administration extended the sleep period but changed the properties of NonREM sleep oscillations (delta, spindle, ripples). Specifically, CBD also led to less long (>100ms) ripples and consequently worse cumulative memory consolidation. In contrast, simple memories were not affected. In sum, we can confirm the beneficial effect of CBD on sleep, however, this comes with changes in NonREM oscillations that negatively impact memory consolidation.
Mice with renal-specific alterations of stem cell-associated signaling develop symptoms of chronic kidney disease but surprisingly no tumors
Authors: Myszczyszyn Adam , Popp Oliver , Kunz Severine , Sporbert Anje , Jung Simone , Penning Louis C. , Fendler Annika , Mertins Philipp , Birchmeier Walter 
Published: March 2023

AbstractPreviously, we found that Wnt and Notch signaling govern stem cells of clear cell kidney cancer (ccRCC) in patients. To mimic stem cell responses in the normal kidney in vitro in a marker-unbiased fashion, we have established organoids from total single adult mouse kidney epithelial cells in Matrigel and serum-free conditions. Deep proteomic and phosphoproteomic analyses revealed that the organoids resembled renewal of adult kidney tubular epithelia, since organoid cells displayed activity of Wnt and Notch signaling, long-term proliferation and expression of markers of proximal and distal nephron lineages. In our wish to model stem cell-derived human ccRCC, we have generated two types of genetic double kidney mutants in mice: Wnt-β-catenin-GOF together with Notch-GOF and Wnt-β-catenin-GOF together with a most common alteration in ccRCC, Vhl-LOF. An inducible Pax8-rtTA-LC1-Cre was used to drive recombination specifically in adult kidney epithelial cells. We confirmed mutagenesis of β-catenin, Notch and Vhl alleles on DNA, protein and mRNA target gene levels. Surprisingly, we observed symptoms of chronic kidney disease (CKD) in mutant mice, but no increased proliferation and tumorigenesis. Thus, the responses of kidney stem cells in the organoid and genetic systems produced different phenotypes, i.e. enhanced renewal versus CKD.
Living Photovoltaics based on Recombinant Expression of MtrA Decaheme in Photosynthetic Bacteria
Authors: Reggente Melania , Schurgers Nils , Mouhib Mohammed , Politi Sara , Antonucci Alessandra , Boghossian Ardemis A. 
Published: March 2023

AbstractAt the center of microbial bioelectricity applications lies the critical need to express foreign heme proteins that are capable of redirecting the electron flux of the cell’s metabolism. This study presents bioengineeredSynechocystissp. PCC 6803 cells capable of increased electrogenicity through the introduction of a genetic construct for cytochrome expression. We could demonstrate the functional expression of the periplasmic MtrA decaheme c-type cytochrome fromShewanella oneidensis, a dissimilatory metal-reducing exoelectrogen, insideSynechocystis. Protein expression was verified through western-blotting and immunostaining, and oxygen evolution, optical density, and absorption measurements confirm sustained cell activity and viability under the tested expression conditions. Furthermore, the bioengineered cells show enhanced mediated exoelectrogenicity, as confirmed through a colorimetric iron assay and electrochemical measurements. Compared to wildtype cells on graphite electrodes, the bioengineered cells show a 2-fold increase in light-dependent, extracellular electron transfer, achieving photocurrent densities of 4 μA/cm2under white light illumination of ∼500 μmol m-2s-1. The increased capacitance obtained under illumination and suppressed photocurrents in the presence of the photosynthetic inhibitor, 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) suggest increased extraction of photosynthetically derived electrons from the recombinant cells. The improved bioelectricity transport across the outer membranes, as achieved through the heterologous heme expression inside cyanobacteria, presents new opportunities for re-wiring the metabolisms of light-harvesting microbes.
Adulis and the transshipment of baboons during classical antiquity
Authors: Grathwol Franziska , Roos Christian , Zinner Dietmar , Hume Benjamin , Porcier Stéphanie M. , Berthet Didier , Cuisin Jacques , Merker Stefan , Ottoni Claudio , Van Neer Wim , Dominy Nathaniel J. , Kopp Gisela H. 
Published: March 2023

AbstractAdulis, located on the Red Sea coast in present-day Eritrea, was a bustling trading centre between the first and seventh centuries CE. Several classical geographers––Agatharchides of Cnidus, Pliny the Elder, Strabo––noted the value of Adulis to Greco-Roman Egypt, particularly as an emporium for living animals, including baboons (Papiospp.). Though fragmentary, these accounts predict the Adulite origins of mummified baboons in Ptolemaic catacombs, while inviting questions on the geoprovenance of older (Late Period) baboons recovered from Gabbanat el-Qurud (“Valley of the Monkeys”), Egypt. Dated to ca. 800–540 BCE, these animals could extend the antiquity of Egyptian-Adulite trade by as much as five centuries. To explore this possibility, we analysed complete mitochondrial genomes from a mummified baboon from Gabbanat el-Qurud and 14 museum specimens with known provenance together with published georeferenced mitochondrial sequence data. Phylogenetic assignment connects the mummified baboon to modern populations ofPapio hamadryasin Eritrea and eastern Sudan. This result, assuming geographical stability of phylogenetic clades, suggests that present-day Eritrea, and by extension Adulis, was a source of baboons for Late Period Egyptians. It also establishes geographic continuity with baboons from the fabled Land of Punt (Dominy et al., 2020), giving weight to speculation that Punt and Adulis were essentially the same trading centres separated by a thousand years of history.
Cancer associated fibroblasts serve as an ovarian cancer stem cell niche through noncanonical Wnt5a signaling
Authors: Fang Yiming , Xiao Xue , Wang Ji , Dasari Subramanyam , Pepin David , Nephew Kenneth P. , Zamarin Dmitriy , Mitra Anirban K. 
Published: March 2023

AbstractFrequent relapse and chemoresistance cause poor outcome in ovarian cancer (OC) and cancer stem cells (CSCs) are important contributors. While most studies focus exclusively on CSCs, the role of the microenvironment in providing optimal conditions to maintain their tumor-initiating potential remains poorly understood. Cancer associated fibroblasts (CAFs) are a major constituent of the OC tumor microenvironment and we show that CAFs and CSCs are enriched following chemotherapy in patient tumors. CAFs significantly increased OC cell resistance to carboplatin. Using heterotypic CAF-OC cocultures andin vivolimiting dilution assay, we confirmed that the CAFs act by enriching the CSC population. CAFs were found to increase the symmetric division of CSCs as well as the dedifferentiation of bulk OC cells into CSCs. The effect of CAFs was limited to OC cells in their immediate neighborhood, which could be prevented by inhibiting Wnt. Analysis of single cell RNA-seq data from OC patients revealed that Wnt5a as the highest expressed Wnt in CAFs and that certain subpopulations of CAFs express higher levels of Wnt5a. We found that Wnt5a from CAFs activated a noncanonical Wnt signaling pathway involving the ROR2/PKC/CERB1 axis in the neighboring CSCs. While canonical Wnt signaling was predominant in interactions between cancer cells in patients, non-canonical Wnt pathway was activated by CAF-OC crosstalk. Treatment with a Wnt5a inhibitor sensitized tumors to carboplatinin vivo. Together, our findings demonstrate a novel mechanism of CSC maintenance by signals from the microenvironmental CAFs, which can be targeted to treat OC chemoresistance and relapse.Statement of significanceCAFs serve as CSC niche through a Wnt5a mediated noncanonical Wnt signaling. Disease relapse and development of chemoresistance is a major problem in OC, which can be potentially addressed by targeting Wnt5a.
A New Behavioral Paradigm for Frustrative Non-reward Reveals a Global Change in Brain Networks by Frustration
Authors: Naik Aijaz Ahmad , Ma Xiaoyu , Munyeshyaka Maxime , Leibenluft Ellen , Li Zheng 
Published: March 2023

AbstractBackgroundIrritability, defined as proneness to anger, can reach a pathological extent. It is a defining symptom of Disruptive Mood Dysregulation Disorder (DMDD) and one of the most common reasons youth presents for psychiatric evaluation and care. Aberrant responses to frustrative non-reward (FNR, the response to omission of expected reward) are central to the pathophysiology of irritability. FNR is a translational construct to study irritability across species. The development of preclinical FNR models would advance mechanistic studies of the important and relatively understudied clinical phenomenon of irritability.MethodsWe used FNR as a conceptual framework to develop a novel mouse behavioral paradigm named Alternate Poking Reward Omission (APRO). After APRO, mice were examined with a battery of behavioral tests and processed for whole brain c-Fos imaging. FNR increases locomotion and aggression in mice regardless of sex. These behavioral changes resemble the symptoms observed in youth with severe irritability. There is no change in anxiety-like, depression-like, or non-aggressive social behaviors. FNR increases c-Fos+ neurons in 13 subregions of thalamus, iso-cortex and hippocampus including the prelimbic, ACC, hippocampus, dorsal thalamus, cuneiform nucleus, pons, and pallidum areas. FNR also shifts the brain network towards a more global processing mode.ConclusionOur novel FNR paradigm produces a frustration effect and alters brain processing in ways resembling the symptoms and brain network reconfiguration observed in youth with severe irritability. The novel behavioral paradigm and identified brain regions lay the groundwork for further mechanistic studies of frustration and irritability in rodents.
DNA nanopores as artificial membrane channels for origami-based bioelectronics
Authors: Luo Le , Manda Swathi , Park Yunjeong , Demir Busra , Vicente Jesse , Anantram M.P. , Oren Ersin Emre , Gopinath Ashwin , Rolandi Marco 
Published: March 2023

SummaryBiological membrane channels mediate information exchange between cells and facilitate molecular recognition1-4. While tuning the shape and function of membrane channels for precision molecular sensing via de-novo routes is complex, an even more significant challenge is interfacing membrane channels with electronic devices for signal readout5-8. This challenge at the biotic-abiotic interface results in low efficiency of information transfer - one of the major barriers to the continued development of high-performance bioelectronic devices9. To this end, we integrate membrane spanning DNA nanopores with bioprotonic contacts to create programmable, modular, and efficient artificial ion-channel interfaces that resolve the ‘iono-electronic’ disparity between the biotic environment and electronics. Through simulations and experiments, we show that cholesterol modified DNA nanopores spontaneously and with remarkable affinity span the lipid bilayer formed over the planar bio-protonic electrode surface and mediate proton transport across the bilayer. Using the ability to easily modify DNA nanostructures, we illustrate that this bioelectronic device can be programmed for electronic recognition of biomolecular signals such as presence of Streptavidin, without disrupting the native environment of the biomolecule. We anticipate this robust biotic-abiotic interface will allow facile electronic measurement of inter-cellular ionic communication and also open the door for active control of cell behavior through externally controlled selective gating of the channels.
Multi-species atlas resolves an axolotl limb development and regeneration paradox
Authors: Zhong Jixing , Aires Rita , Tsissios Georgios , Skoufa Evangelia , Brandt Kerstin , Sandoval-Guzmán Tatiana , Aztekin Can 
Published: March 2023

AbstractHumans and other tetrapods are considered to require apical-ectodermal-ridge, AER, cells for limb development, and AER-like cells are suggested to be re-formed to initiate limb regeneration. Paradoxically, the presence of AER in the axolotl, the primary regeneration model organism, remains controversial. Here, by leveraging a single-cell transcriptomics-based multi-species atlas, composed of axolotl, human, mouse, chicken, and frog cells, we first established that axolotls contain cells with AER characteristics. Surprisingly, further analyses and spatial transcriptomics revealed that axolotl limbs do not fully re-form AER cells during regeneration. Moreover, the axolotl mesoderm displays part of the AER machinery, revealing a novel program for limb (re)growth. These results clarify the debate about the axolotl AER and the extent to which the limb developmental program is recapitulated during regeneration.