bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccine-hesitant people misperceive the social norm of vaccination
Authors: Vriens Eva , Tummolini Luca , Andrighetto Giulia
Published: April 2023

Vaccine hesitancy is one of the main threats to global health, as became clear once more during the COVID-19 pandemic. Vaccination campaigns could benefit from appeals to social norms to promote vaccination, but without awareness of the social norm in place any intervention relying on social norms may backfire. We present a two-step approach of social norm diagnosis and intervention that identifies both whether a vaccination norm exists or develops over time and corrects misperceptions. In two studies (N=887 and N=412) conducted in Rome, Italy from June to August 2021 (during the first COVID-19 vaccination campaign), we show that vaccine-hesitant people strongly underestimated vaccine acceptance rates for COVID-19 despite increases in region-wide vaccination rates. This suggests a false consensus bias on the social norm of vaccination. We presented a subgroup of vaccine-hesitant people with the accurate vaccine acceptance rates (both planned uptake and vaccine approval) and tested if this social information would lower their vaccine hesitancy. We do not find clear effects, most likely because of the introduction of the COVID-19 health certificate (the “green pass”) that was implemented during our data collection. The green pass reduced both misperceptions in the social norm and vaccine hesitancy, thus undermining our treatment effect. We conclude that to alleviate misperceptions on the social norm of vaccination in early stages of the vaccination campaign governments and media should report not just the current vaccination rate, but also about vaccination intentions and approval.
Movable but unavoidable nodal lines through high-symmetry points in 2D materials
Authors: Damljanović Vladimir
Published: April 2023

In 2D materials, electronic band contacts often make a non-trivial contribution to a material’s topological properties. Besides band contacts at high-symmetry points (HSPs) in the Brillouin zone (BZ), like those in graphene, there are nodal lines that form various patterns in the reciprocal space. In this paper we have found all movable nodal lines, whose shape depends on the model, that pass through HSPs in the presence of time-reversal symmetry. Cases with and without spin–orbit coupling are included by studying all 80 layer groups and their double extensions. Eight single and six double groups, including three symmorphic, necessarily host Dirac and Weyl nodal lines that extend through the whole BZ, respectively. Our research might be of interest in designing new materials with interesting physical properties.
Characteristics of women presenting with hepatitis B at antenatal care services in London, 2008–2018
Authors: Wilson A , Anderson C , Mindlin M , Sawyer C , Verlander N Q , Hiironen I , Forde J , Paranthaman K , Chandra N L
Published: April 2023

Background

To support interventions to prevent mother-to-child transmission of hepatitis B and fill gaps in surveillance, the Enhanced Surveillance of Antenatal Hepatitis B (ESAHB) programme was implemented in London from 2008 to 2018 to collect demographic information on women who tested positive for hepatitis B during antenatal screening. We describe the epidemiology of hepatitis B in pregnancy, as reported to ESAHB.

Methods

The characteristics of pregnant women living with hepatitis B were described and rates were calculated by year, local authority and residence deprivation decile (1 being most deprived). Poisson regression tested the association between pregnant women living with hepatitis B and deprivation decile.

Results

Between 2008 and 2018, 8879 women living with hepatitis B in London (0.35 per 1000 women) reported 11 193 pregnancies. Annual hepatitis B rates remained stable, but there was strong evidence for an inverse association between rate and deprivation decile (P < 0.001). The majority of women in the cohort presented late to antenatal care, were born outside the UK in a hepatitis B endemic area or required an interpreter for consultations.

Conclusions

ESAHB provided important data to inform service quality improvements for women living with hepatitis B. This analysis highlights the link between deprivation and hepatitis B.
Earlier chronotype in midlife as a predictor of accelerated brain aging: a population-based longitudinal cohort study
Authors: Kim Hyeon Jin , Kim Regina E Y , Kim Soriul , Lee Seung Ku , Lee Hyang Woon , Shin Chol
Published: April 2023

Study Objectives

Evidence suggests that sleep–wake cycle disruption could be an early manifestation of neurodegeneration and might even be a risk factor for developing diseases in healthy adults. We investigated the impact of circadian phase change on structural and functional brain deterioration in a late-adulthood population.

Methods

We analyzed the data of 1874 participants (mean age 58.6 ± 6.3 years, 50.3% female) from the Korean Genome and Epidemiology Study, who were identified as cognitively unimpaired. The mid-sleep time on free days corrected for sleep debt on workdays (MSFsc) at baseline was adopted as an indicator of the chronotype and used to categorize the participants into three groups. The relationships between the chronotype and longitudinal changes in the gray matter volume (GMV) and cognitive function were investigated (mean interval: 4.2 ± 0.5 years).

Results

The mean MSFsc of the participants was 2:45 am. The earlier MSFsc was linearly associated with smaller right entorhinal GMV (β [SE] = 0.02 [0.01]; p = .001) and lower visual memory function test scores at baseline. Longitudinally, the earlier MSFsc at baseline was only significantly associated with more rapid atrophy in the temporal lobe (β [SE] = 0.18 [0.07]; p = .018) and not with other brain lobes or subregions. Moreover, the earlier MSFsc was associated with more deteriorated verbal learning and visual memory function test scores.

Conclusions

An earlier chronotype in midlife, measured using a questionnaire, can be a valuable indicator for individuals who should be closely monitored for the development of neurodegenerative disorders.
Ethnicity, Imprisonment, and Confidence in Police and Courts: Evidence from an International Survey
Authors: O’Brien Timothy L
Published: April 2023

This article investigates the sources of ethnic disparities in confidence in police and courts. After reviewing studies of ethnicity and trust in legal authorities and comparative research on prisons, I argue that ethnic divides in confidence in police and courts are based on power imbalances between majority and minority groups and exacerbated by punitive legal systems. I test these claims using data from waves 6 and 7 of the World Values Survey, including 99,480 people in 59 countries. Results from mixed effects logistic regressions indicate that, overall, ethnic majority group members are more likely than minority group members to be confident in police and in courts. However, the differences are larger in countries with higher imprisonment rates. In fact, there are no ethnic differences in confidence in police or courts in countries with low imprisonment rates. The patterns remain net of individual- and country-level controls for crime and other factors. These results suggest that ethnic disparities in confidence in legal authorities are rooted in power dynamics intrinsic to the minority-majority dichotomy and that punitive legal authorities amplify the divides.
Black Boys’ Perceptions of Depression and Mental Health: Findings from the YBMen Project
Authors: Williams Ed-Dee G , Casanova Allura , Watkins Daphne C
Published: April 2023

Despite growing research dedicated to investigating the mental health of Black boys, few directly examine experiences with their perceptions and understanding of mental health conditions such as depression. This study uses data from a social media-based intervention for Black males, the Young Black Men, Masculinities, and Mental Health project. In a focus group with 8th-grade Black boys, facilitators asked open-ended questions about perceptions of mental health and depression, views of manhood, and experiences with social support. Findings revealed this group of Black boys – while well versed in many of the causes, symptoms, and treatments for mental health challenges and depression – preferred to address mental health needs on their own and through informal familial support. It also revealed the boys wrestled with the complex ways in which their racial identity would affect their experiences with mental health. The findings speak to the importance of mental health education for Black boys and the need for further research incorporating Black boys’ voices in their perceptions, experiences, and understandings of mental health. Finally, the study connects Black boys’ perspectives with many of the perspectives of their racially diverse peers.
Endogenous Bone Marrow-Derived Stem Cell Mobilization and Homing for In Situ Tissue Regeneration
Authors: Chen Yunzi , Li Ye , Lu Feng , Dong Ziqing
Published: April 2023

In mammals, post-injury repair and regenerative events rely predominantly on stem cell function. Stem cell transplantation has achieved considerable success in animals but remains unfavorable for humans because of the unavoidable drawbacks. Nevertheless, substantial evidence suggests the regenerative potential of endogenous stem cells can be improved for functional and structural recovery of tissue damage or in disease conditions. Endogenous stem cells are mostly quiescent under steady-state conditions and reside in their niche. Once faced with tissue injury, physiological and molecular changes within the niche or from distant tissues activate the migration, proliferation, and differentiation of stem cells, contributing to tissue repair. Tissue regeneration is augmented by artificially amplifying the factors that promote stem cell mobilization or enhance the homing of endogenous stem cells. This cell-free strategy, known as “in situ tissue regeneration,” represents a safer and more efficient means to conduct tissue regeneration. Bone marrow (BM) is considered the central niche and main reservoir of many types of stem cells. These stem cells hold great therapeutic potential for the regeneration of multiple injured tissues. Herein, we review recent strategies for promoting in situ tissue regeneration through BM-derived stem cell mobilization or homing in animal models as well as in human trials. With the advancement in biomaterial engineering, chemoattractant signals combined with functionalized bioscaffolds have accomplished sustained activation of endogenous BM-derived stem cells that can be used as an attractive strategy for efficient in situ tissue regeneration.
Subconjunctival Administration of Mesenchymal Stem Cells Alleviates Ocular Inflammation in a Murine Model of Corneal Alkali Burn
Authors: Chen Mingxiong , Chen Xiaoniao , Li Xiaoqi , Wang Junyi , Wu Jie , Wang Qun , Huang Yifei , Li Zongjin , Wang Liqiang
Published: April 2023

Corneal alkali burns cause extensive damage not only to the cornea but also to the intraocular tissues. As an anti-inflammatory therapy, subconjunctival administration of mesenchymal stem cells (MSCs) for corneal protection after corneal alkali burn has been explored. Little evidence demonstrates the potential of subconjunctival MSCs delivery in protecting the post-burn intraocular tissues. This study aimed to evaluate the therapeutic efficacy of subconjunctival injection of human placental (hP)-MSCs in protecting against ocular destruction after the burn. hP-MSCs were subconjunctivally administered to C57/BL mice after corneal alkali burn. Western blot of iNOS and CD206 was performed to determine the M1 and M2 macrophage infiltration in the cornea. Infiltration of inflammatory cells in the anterior uvea and retina was analyzed by flow cytometry. The TUNEL assay or Western blot of Bax and Bcl2 was used to evaluate the anti-apoptotic effects of MSCs. MSCs could effectively facilitate cornea repair by suppressing inflammatory cytokines IL-1β, MCP-1, and MMP9, and polarizing CD206 positive M2 macrophages. Anterior uveal and retinal inflammatory cytokines expression and inflammatory cell infiltration were inhibited in the MSC-treated group. Reduced TUNEL positive staining and Bax/Bcl2 ratio indicated the anti-apoptosis of MSCs. MSC-conditioned medium promoted human corneal epithelial cell proliferation and regulated LPS-stimulated inflammation in RAW 264.7 macrophages, confirming the trophic and immunoregulatory effects of MSCs. Our findings demonstrate that subconjunctival administration of MSCs exerted anti-inflammatory and anti-apoptotic effects in the cornea, anterior uvea, and retina after corneal alkali burn. This strategy may provide a new direction for preventing post-event complications after corneal alkali burn.
Genomic epidemiology of the rotavirus G2P[4] strains in coastal Kenya pre- and post-rotavirus vaccine introduction, 2012–8
Authors: Makori Timothy O , Bargul Joel L , Lambisia Arnold W , Mwanga Mike J , Murunga Nickson , de Laurent Zaydah R , Lewa Clement S , Mutunga Martin , Kellam Paul , Cotten Matthew , Nokes D James , Phan My , Agoti Charles N
Published: April 2023

The introduction of rotavirus vaccines into the national immunization programme in many countries has led to a decline in childhood diarrhoea disease burden. Coincidentally, the incidence of some rotavirus group A (RVA) genotypes has increased, which may result from non-vaccine-type replacement. Here, we investigate the evolutionary genomics of rotavirus G2P[4] which has shown an increase in countries that introduced the monovalent Rotarix® vaccine. We examined sixty-three RVA G2P[4] strains sampled from children (aged below 13 years) admitted to Kilifi County Hospital, coastal Kenya, pre- (2012 to June 2014) and post-(July 2014 to 2018) rotavirus vaccine introduction. All the sixty-three genome sequences showed a typical DS-1-like genome constellation (G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2). Pre-vaccine G2 sequences predominantly classified as sub-lineage IVa-3 and co-circulated with low numbers of sub-lineage IVa-1 strains, whereas post-vaccine G2 sequences mainly classified into sub-lineage IVa-3. In addition, in the pre-vaccine period, P[4] sub-lineage IVa strains co-circulated with low numbers of P[4] lineage II strains, but P[4] sub-lineage IVa strains predominated in the post-vaccine period. On the global phylogeny, the Kenyan pre- and post-vaccine G2P[4] strains clustered separately, suggesting that different virus populations circulated in the two periods. However, the strains from both periods exhibited conserved amino acid changes in the known antigenic epitopes, suggesting that replacement of the predominant G2P[4] cluster was unlikely a result of immune escape. Our findings demonstrate that the pre- and post-vaccine G2P[4] strains circulating in Kilifi, coastal Kenya, differed genetically but likely were antigenically similar. This information informs the discussion on the consequences of rotavirus vaccination on rotavirus diversity.
A widespread Ponto-Caspian invader with a mistaken identity: integrative taxonomy elucidates the confusing taxonomy ofTrichogammarus trichiatus(=Echinogammarus) (Crustacea: Amphipoda)
Authors: Copilaș-Ciocianu Denis , Palatov Dmitry , Rewicz Tomasz , Sands Arthur F , Arbačiauskas Kęstutis , van Haaren Ton , Hebert Paul D N , Grabowski Michał , Marin Ivan
Published: April 2023

Amphipods have diversified greatly in the Ponto-Caspian region. Although many of these species are prominent invaders their systematics remains unclear. Taking an integrative approach, we investigate the taxonomy of Trichogammarus trichiatus, a widespread invader in European inland waters. It was initially described from the north-eastern Black Sea coast as Chaetogammarus trichiatus by Martynov in 1932. A similar taxon, Chaetogammarus tenellus major, was described by Cărăușu from the western Black Sea in 1943 but later synonymized with C. trichiatus. Chaetogammarus trichiatus was itself shuffled between Chaetogammarus and the Atlanto-Mediterranean Echinogammarus, currently being assigned to Trichogammarus. Our analyses (six DNA markers, 60 measurements and scanning electron microscopic imaging) reveal that T. trichiatus and C. tenellus major are distinct species; the former is a Caucasian endemic, whereas the latter invaded Europe. Unexpectedly, T. trichiatus is an incipient species molecularly nested in Chaetogammarus ischnus, despite pronounced morphological and geographical differentiation. We also recover Chaetogammarus as polyphyletic, yet its member species are nested in the Ponto-Caspian radiation, thus distinct from Echinogammarus. Consequently, we reassign T. trichiatus to Chaetogammarus (Chaetogammarus trichiatus), synonymize Trichogammarus with Chaetogammarus and place C. tenellus major in the new genus Spirogammarus gen. nov. (Spirogammarus major comb. & stat. nov.). Chaetogammarus necessitates further systematic refinement.
Recombinase Polymerase Amplification Did Not Detect Xylella fastidiosa subsp. multiplex in Peach Seeds from Phony Peach Disease Trees
Authors: Johnson Kendall A. , Chen Chunxian , Bock Clive H. , Brannen Phillip M.
Published: April 2023

Phony peach disease (PPD), caused by Xylella fastidiosa (Xf) subspecies multiplex, is an important disease of peach in the southeastern United States. Seed transmission of Xf has not been reported for PPD, and research published in 1933 indicated that seedlings grown from seeds of PPD trees did not develop the disease. Recombinase polymerase amplification is a relatively new and rapid molecular detection process that has been commercialized as AmplifyRP XRT+ for Xf. We utilized this test to determine whether the Xf bacterium could be detected in peach seeds collected from PPD-infected trees. Initially, 25 seeds and 25 excised embryos were individually tested for Xf using qPCR, and Xf was not detected. In a more extensive study, 300 individual seeds were tested for Xf using recombinase polymerase amplification, and all seeds were again negative for Xf. Our studies provide no new evidence to support vertical transmission of Xf from Xf-infected peach trees to peach seeds. However, before concluding that vertical transmission does not occur, additional studies to observe and test seedlings produced from seeds collected from PPD trees should be conducted.
Changing Characteristics of Children With COVID-19 in Colorado Admitted During Different Variant Periods
Authors: Jelic Monika , Silveira Lori , Lang Sean , Curran-Hays Shane , Boyer Shea , Carter Brian , Choi Ye Ji , Fresia Joellen , Maeda Lilia C. , Nerguizian David , Graff Kelly , Abuogi Lisa , Smith Christiana ,   for the Children and COVID-19 in Colorado study
Published: April 2023

Background:

Data are lacking on the impact of different severe acute respiratory syndrome coronavirus 2 variants in children and on pediatric vaccine effectiveness. We examined differences among children requiring hospital admission associated with coronavirus disease 2019 (COVID-19) during wild type, Delta and Omicron variant periods and calculated vaccine effectiveness at preventing symptomatic hospitalization during the Delta and Omicron variant periods.

Methods:

We conducted a retrospective review of children younger than 21 years of age hospitalized with symptomatic COVID-19. Characteristics were compared between variant periods using Kruskal–Wallis or generalized Fisher exact tests. We estimated vaccine effectiveness in preventing symptomatic hospitalization.

Results:

We included 115 children admitted during the wild type period, 194 during Delta and 226 during the Omicron periods. Median age (years) decreased (12.2 wild type, 5.9 Delta, 1.3 Omicron periods, P < 0.0001) over time. Children were less likely to have a comorbid condition, including diabetes or obesity, and had shorter admissions during Omicron compared with the wild type and Delta periods. Intensive care unit admissions and respiratory support requirements were highest during the Delta period (P = 0.05). Among children ≥12 years, adjusted vaccine effectiveness at preventing symptomatic hospitalization was 86% during Delta and 45% during Omicron periods.

Conclusion(s):

Children hospitalized with COVID-19 during later variant periods were younger and less likely to have comorbidities. Children admitted during the Delta variant period required more intensive care and respiratory support compared to other variant periods. Vaccination was less effective at preventing symptomatic hospital admission during the Omicron period compared to the Delta period.
Increasing Rates of Pancreatic and Hepatocellular Cancers Parallel Increasing Obesity Rates
Authors: Kumar Shria , Moghaddam Saltenat , Goldberg David S. , Mantero Alejandro , Crane Tracy E.
Published: April 2023

Objectives

Gastrointestinal (GI) cancers are now the second leading cause of cancer death in the United States, and six are convincingly associated with obesity. We interrogate the association of a state's obesity prevalence with cancer incidence.

Methods

We use data from US Cancer Statistics for each of the 6 cancers of interest from 2011 to 2018. Age-adjusted incidences were calculated, and the Behavioral Risk Factor Surveillance System was used to identify prevalence of obesity in each state. A generalized estimating equation model was used to relate the rate of cancer with the rate of obesity.

Results

Increased state-level prevalence of obesity was significantly associated with increasing state-level incidence of pancreatic and hepatocellular cancers. The rate of colorectal cancer was not associated with increasing obesity in 2011–2014 but from 2015 to 2018 was inversely associated with increasing rates of obesity. State-level prevalence of obesity was not associated with esophageal, gastric, or gallbladder cancers.

Conclusions

Weight management interventions may reduce risk of pancreatic and hepatocellular cancers.
LEVEL OF PROFESSIONAL AWARENESS AMONG HEALTH RECORD OFFICERS IN BAYELSA STATE AND THEIR IMPLICATIONS FOR PATIENT CARE, HEALTH SYSTEMS, AND HEALTH POLICY
Authors: Erezina Ahoada Esther , Raimi Aziba-anyam Gift , Emmanuel Odipe Oluwaseun , Raimi Morufu Olalekan , Abaya Samuel Terungwa , Kakwi Daniel Josephine
Published: April 2023

  

Background

As Electronic health records (EHRs) become more commonplace, and are expected to play a key role in improving the quality of Nigeria health care. Thus, EHRs can improve quality of care delivery in numerous ways such as providing accurate and up-to-date patient information and medical knowledge, rapid retrieval of health information, ability to exchange health information to all authorized participants within or across organizations, automated clinical reminders, improved adherence to treatment guidelines, and accumulation of data for quality monitoring and improvement. Based on regulatory and governmental recommendations, the EHR is being adapted in an increasing number of academic institutions (NDUTH), government hospitals (FMC) and private practice settings. It is incumbent upon HIM leadership to ensure students are skillful users of the technologies that will be in place as they care for patients.

Objectives:

This study aimed to explore, identify and understand critical awareness of electronic health records management level as a means of ensuring confidentiality in public health care sector (FMC & NDUTH) in Bayelsa State, Nigeria.

Methods: 

The cross-sectional descriptive design was used and a total of 159 health professionals who represented a variety of user groups across different specialties within the hospital completed the questionnaire. The collected data were analyzed. both descriptively and inferentially. Frequency and percentages were used to analysed the data and the result presented in tables. Data analysis was facilitated using the Statistical Package for Social Sciences (SPSS version 20.0).

Results: 

Majority of the respondents (90.6%) were aware of the electronic health record management among health record officers. 

Conclusions: 

To ensure continuity of care, it is necessary to develop educational and manageable program to improve EHR awareness. The findings may inform other hospitals and healthcare systems on actions that can be taken prior to EHR implementation to reduce concerns for quality, confidentiality, safety of patient care and improve the chance of successful implementation.
Asthma exacerbations and eosinophilia in the UK Biobank: a Genome-Wide Association Study
Authors: Edris Ahmed , Voorhies Kirsten , Lutz Sharon M. , Iribarren Carlos , Hall Ian , Wu Ann Chen , Tobin Martin , Fawcett Katherine , Lahousse Lies
Published: April 2023

Asthma exacerbations reflect disease severity, affect morbidity and mortality, and may lead to declining lung function. Inflammatory endotypes (e.g.:T2-high (eosinophilic)) may play a key role in asthma exacerbations. We aimed to assess whether genetic susceptibility underlies asthma exacerbation risk and additionally tested for an interaction between genetic variants and eosinophilia on exacerbation risk.

UK Biobank data were used to perform a GWAS study of individuals with asthma and at least one exacerbation compared to individuals with asthma and no history of exacerbations. Individuals with asthma were identified using self-reported data, hospitalization data and General Practitioners (GP) records. Exacerbations were identified as either asthma–related hospitalization, GP record of asthma exacerbation, or an oral corticosteroid (OCS) burst prescription. A logistic regression model adjusted for age, sex, smoking status, and genetic ancestry via principal components was used to assess the association between genetic variants and asthma exacerbations. We sought replication for suggestive associations (P<5x10-6) in the GERA cohort.

In the UK Biobank, we identified 11,604 cases, and 37,890 controls. While no variants reached genome wide significance (P<5x10-8) in the primary analysis, 116 signals were suggestively significant (P<5x10-6). In GERA, two SNPs (rs34643691 and rs149721630) were nominally significant and showed the same direction of effect.

Two novel genetic loci-(NTRK3 and ABCA13)-that are reproducibly associated with asthma exacerbation in participants with asthma were identified. Confirmation of these findings in different asthma (or ancestry) sub-populations and functional investigation will be required to understand their mechanisms of action and potentially inform therapeutic development.
Mechanism of glucocorticoid receptor activation regulated expression of thrombospondin-1
Authors: Wang Yan-Yan , Song Yi-Yi , Jiang Wen-Yi , Zhang Hao-Tian , Chen Jing-Wei , Murao Koji , Sun Wan-Ping , Zhang Guo-Xing
Published: April 2023

Objective:Thrombospondin-1 (TSP-1) plays an important role in platelet activation and aggregation and aggravates thrombosis. Chronic stress can cause a variety of diseases, including coagulation disorders, increased thrombosis, atherosclerosis, and a series of cardiovascular and cerebrovascular diseases. However, it is still unknown how chronic stress regulates the expression of TSP-1 after glucocorticoid receptor activation.

Approach and Results:rats chronic unpredictable mild stress model was applied and the changes of TSP-1 and microRNAs in plasma were examined. Effects of glucocorticoid receptor activation on human umbilical vein endothelial cells and platelets were observed. Glucocorticoid receptor (GR) activation upregulated the expression of TSP-1 and downregulated the expression of microRNA-1-3p accompanied with increase of phosphorylation of p38 mitogen-activated protein kinase (MAPK) and argonaute-2 (AGO-2). Blockade of p38 MAPK phosphorylation resulted in decrease of phosphorylation level of AGO-2, increase of microRNA-1-3p expression, and decrease of TSP-1 expression. Transfection of AGO-2 Y393F point mutant plasmid, increased microRNA-1-3p expression and decreased TSP-1 expression, transfection of microRNA-1-3p mimic also decreased TSP-1 expression, while transfection of microRNA-1-3p inhibitor increased TSP-1 expression. Finally, GR activation led to an increase in the phosphorylation level of p38 MAPK in platelets and an increase in the level of TSP-1 in the supernatant.

Conclusions:our study demonstrates that GR activation in HUVEC stimulates the phosphorylation of p38 MAPK, which in turn promotes the phosphorylation of AGO-2 and inhibits the maturation of microRNA-1-3p, leading to elevated expression of TSP-1, GR activation in platelets leads to the release of TSP-1.

Abstract Figure

Graphical Abstract

HSS: Hydrocortisone sodium succinate
Synergistic Screening of Peptide-Based Biotechnological Drug Candidates for Neurodegenerative Diseases using Yeast Display and Phage Display
Authors: Özçelik Cemile Elif , Beğli Özge , Hınçer Ahmet , Ahan Recep Erdem , Kesici Mehmet Seçkin , Kasırga Talip Serkan , Özçubukçu Salih , Şeker Urartu Özgür Şafak
Published: April 2023

Peptide therapeutics are robust and promising molecules for treating diverse disease conditions. These molecules can be developed from naturally occurring or mimicking native peptides, through rational design and peptide libraries. We developed a new platform for the rapid screening of the peptide therapeutics for disease targets. In the course of the study, we aimed to employ our platform to screen a new generation of peptide therapeutics candidates against aggregation prone protein targets. Two peptide drug candidates for the protein aggregation prone diseases namely Parkinson’s and Alzheimer’s diseases were screened. Currently, there are several therapeutic applications that are only effective in masking or slowing down symptom development. Nonetheless, different approaches are developed for inhibiting amyloid aggregation in the secondary nucleation phase, which is critical for amyloid fibril formation. Instead of targeting secondary nucleated protein structures, we tried to inhibit monomeric amyloid units as a novel approach for halting disease-condition. To achieve this, we combined yeast surface display and phage display library platforms. We expressed α-synuclein, amyloid β40, and amyloid β42on yeast surface, and we selected peptides by using phage display library. After iterative biopanning cycles optimized for yeast cells, several peptides were selected for interaction studies. All of the peptides have been usedin vitrocharacterization methods which are QCM-D measurement, AFM imaging, and ThT assay, and they have yielded promising results in order to block fibrillization or interact with amyloid units as a sensor molecule candidate. Therefore, peptides are good choice for diverse disease-prone molecule inhibition particularly those inhibiting fibrillization. Additionally, these selected peptides can be used as drugs and sensors to detect disease quickly and halt disease progression.

Abstract Figure
Eco-evolutionary feedbacks shape the evolution of constitutive and inducible defences
Authors: Watson Bridget N. J. , Pursey Elizabeth , Gandon Sylvain , Westra Edze R.
Published: April 2023

Organisms have evolved a range of constitutive (always active) and inducible (elicited by parasites) defence mechanisms, but we have limited understanding of what drives the evolution of these orthogonal defence strategies. Bacteria and their phages offer a tractable system to study this: bacteria can acquire constitutive resistance by mutation of the phage receptor (surface mutation,sm) or induced resistance through their CRISPR-Cas adaptive immune system. Using a combination of theory and experiments we demonstrate that the mechanism that establishes first has a strong advantage because it weakens selection for the alternative resistance mechanism. As a consequence, ecological factors that alter the relative frequencies at which the different resistances are acquired have a strong and lasting impact: high growth conditions promote the evolution ofsmresistance by increasing the influx of receptor mutation events during the early stages of the epidemic, whereas a high infection risk during this stage of the epidemic promotes the evolution of CRISPR immunity, since it fuels the (infection-dependent) acquisition of CRISPR immunity. This work highlights the strong and lasting impact of the transient evolutionary dynamics during the early stages of an epidemic on the long-term evolution of constitutive and induced defences, which may be leveraged to manipulate phage resistance evolution in clinical and applied settings.
β1 integrin signaling governs necroptosis via the chromatin remodeling factor CHD4
Authors: Sun Zhiqi , Cernilogar Filippo M. , Horvatic Helena , Yeroslaviz Assa , Abdullah Zeinab , Schotta Gunnar , Hornung Veit
Published: April 2023

Fibrosis, characterized by sustained activation of myofibroblasts and excessive extracellular matrix (ECM) deposition, is known to be associated with chronic inflammation. RIPK3, the central kinase of necroptosis signaling, is upregulated in fibrosis and contributes to the TNF-mediated inflammation. In bile duct ligation-induced liver fibrosis, we found that myofibroblasts are the major cell type expressing RIPK3. Genetic ablation of β1 integrins, the major profibrotic ECM receptors in fibroblasts, not only abolished ECM fibrillogenesis but also blunted RIPK3 expression via an epigenetic mechanism mediated by the chromatin remodeling factor CHD4. While the function of CHD4 has been conventionally linked to NuRD and ChAHP complexes, we found that CHD4 potently repressed a set of genes, includingRipk3, with high locus specificity but independent of either the NuRD or ChAHP complex. Thus, our data uncover that β1 integrin intrinsically links fibrotic signaling to RIPK3-driven inflammation via a novel mode of action of CHD4.
LSD microdosing attenuates the impact of temporal priors in time perception
Authors: Sadibolova Renata , Murray-Lawson Clare , Family Neiloufar , Williams Luke T. J. , Luke David P. , Terhune Devin B.
Published: April 2023

Recent theoretical work embedded within the predictive processing framework has proposed that the neurocognitive and therapeutic effects of psychedelics are driven by the modulation of priors (Carhart-Harris & Friston, 2019). We conducted pre-registered re-analyses of previous research (Yanakieva et al., 2019) to examine whether microdoses of lysergic acid diethylamide (LSD) alleviate the temporal reproduction bias introduced by priors, as predicted by this theoretical framework. In a between-groups design, participants were randomly assigned to one of four groups receiving LSD (5, 10, or 20 μg) or placebo (0 μg) and completed a visual temporal reproduction task spanning subsecond to suprasecond intervals (0.8 to 4 sec). Using mixed-effects modelling, we evaluated the impact of the treatment group, and of the overall history of stimulus intervals (globalpriors) and the local stimulus history (localpriors), weighted by their respective precision weights (inverse of variance), on temporal reproduction. Our principal finding was that the precision-weighted local priors and their precision weights reduced the under-reproduction bias observed under LSD in the original research. Furthermore, controlling for the precision- weighted local prior eliminated the reduced temporal reproduction bias under LSD, indicating that LSD microdosing mitigated the temporal under-reproduction by reducing the relative weighting of priors. These results suggest that LSD microdosing alters human time perception by decreasing the influence of local temporal priors.
Gap junctions in Turing-type periodic feather pattern formation
Authors: Tseng Chun-Chih , Woolley Thomas E. , Jiang Ting-Xin , Wu Ping , Maini Philip K. , Widelitz Randall B. , Chuong Cheng-Ming
Published: April 2023

Periodic patterning requires coordinated cell-cell interactions at the tissue level. Turing showed, using mathematical modeling, how spatial patterns could arise from the reactions of a diffusive activator-inhibitor pair in an initially homogenous two-dimensional field. Most activators and inhibitors studied in biological systems are proteins, and the roles of cell-cell interaction, ions, bioelectricity, etc. are only now being identified. Gap junctions (GJs) mediate direct exchanges of ions or small molecules between cells, enabling rapid long-distance communications in a cell collective. They are therefore good candidates for propagating non-protein-based patterning signals that may act according to the Turing principles. Here, we explore the possible roles of GJs in Turing-type patterning using feather pattern formation as a model. We found seven of the twelve investigated GJ isoforms are highly dynamically expressed in the developing chicken skin.In ovofunctional perturbations of the GJ isoform, connexin 30, by siRNA and the dominant-negative mutant applied before placode development led to disrupted primary feather bud formation, including patches of smooth skin and buds of irregular sizes. Later, after the primary feather arrays were laid out, inhibition of gap junctional intercellular communication in theex vivoskin explant culture allowed the emergence of new feather buds in temporal waves at specific spatial locations relative to the existing primary buds. The results suggest that gap junctional communication may facilitate the propagation of long-distance inhibitory signals. Thus, the removal of GJ activity would enable the emergence of new feather buds if the local environment is competent and the threshold to form buds is reached. We propose Turing-based computational simulations that can predict the appearance of these ectopic bud waves. Our models demonstrate how a Turing activator-inhibitor system can continue to generate patterns in the competent morphogenetic field when the level of intercellular communication at the tissue scale is modulated.
Activation loop plasticity and active site coupling in the MAP kinase, ERK2
Authors: Pegram Laurel , Riccardi Demian , Ahn Natalie
Published: April 2023

Changes in the dynamics of the protein kinase, ERK2, have been shown to accompany its activation by dual phosphorylation. However, our knowledge about the conformational changes represented by these motions is incomplete. Previous NMR relaxation dispersion studies showed that active, dual-phosphorylated ERK2 undergoes global exchange between at least two energetically similar conformations. These findings, combined with measurements by hydrogen exchange mass spectrometry (HX-MS), suggested that the global conformational exchange involves motions of the activation loop (A-loop) that are coupled to regions surrounding the kinase active site. In order to better understand the contribution of dynamics to the activation of ERK2, we applied long conventional molecular dynamics (MD) simulations starting from crystal structures of active, phosphorylated (2P), and inactive, unphosphorylated (0P) ERK2. Individual trajectories were run for (5 to 25)µs and totaled 727µs. The results showed that the A-loop is unexpectedly flexible in both 2P- and 0P-ERK2, and able to adopt multiple long-lived (>5µs) conformational states. Simulations starting from the X-ray structure of 2P-ERK2 (2ERK) revealed A-loop states corresponding to restrained dynamics within the N-lobe, including regions surrounding catalytic residues. One A-loop conformer forms lasting interactions with the C-terminal L16 segment and shows reduced RMSF and greater compaction in the active site. By contrast, simulations starting from the most common X-ray conformation of 0P-ERK2 (5UMO) reveal frequent excursions of A-loop residues away from a C-lobe docking site pocket and towards a new state that shows greater dynamics in the N-lobe and disorganization around the active site. Thus, the A-loop in ERK2 appears to switch between distinct conformational states that reflect allosteric coupling with the active site, likely occurringviathe L16 segment. Analyses of crystal packing interactions across many structural datasets suggest that the A-loop observed in X-ray structures of ERK2 may be driven by lattice contacts and less representative of the solution structure. The novel conformational states identified by MD expand our understanding of ERK2 regulation, by linking the activated state of the kinase to reduced dynamics and greater compaction surrounding the catalytic site.
Inferring parameters of pyramidal neuron excitability in mouse models of Alzheimer’s disease using biophysical modeling and deep learning
Authors: Saghafi Soheil , Rumbell Timothy , Gurev Viatcheslav , Kozloski James , Tamagnini Francesco , Wedgwood Kyle C. A. , Diekman Casey O.
Published: April 2023

Alzheimer’s disease (AD) is believed to occur when abnormal amounts of the proteins amyloid beta and tau aggregate in the brain, resulting in a progressive loss of neuronal function. Hippocampal neurons in transgenic mice with amyloidopathy or tauopathy exhibit altered intrinsic excitability properties. We introduce a novel parameter inference technique, deep hybrid modeling (DeepHM), that combines deep learning with biophysical modeling to map experimental data recorded from hippocampal CA1 neurons in transgenic AD mice and age-matched wildtype littermate controls to the parameter space of a conductance-based CA1 model. Although mechanistic modeling and machine learning methods are by themselves powerful tools for approximating biological systems and making accurate predictions from data, when used in isolation these approaches suffer from distinct shortcomings: model and parameter uncertainty limit mechanistic modeling, whereas machine learning methods disregard the underlying biophysical mechanisms. DeepHM addresses these shortcomings by using conditional generative adversarial networks (cGANs) to provide an inverse mapping of data to mechanistic models that identifies the distributions of mechanistic modeling parameters coherent to the data. Here, we demonstrate that DeepHM accurately infers parameter distributions of the conductance-based model and outperforms a Markov chain Monte Carlo method on several test cases using synthetic data. We then use DeepHM to estimate parameter distributions corresponding to the experimental data and infer which ion channels are altered in the Alzheimer’s mouse models compared to their wildtype controls at 12 and 24 months. We find that the conductances most disrupted by tauopathy, amyloidopathy, and aging are delayed rectifier potassium, transient sodium, and hyperpolarization-activated potassium, respectively.
From scalp to cortex, the whole isn’t greater than the sum of its parts: introducing GetTissueThickness (GTT) to assess age and sex differences in tissue thicknesses
Authors: Van Hoornweder Sybren , Geraerts Marc , Verstraelen Stefanie , Nuyts Marten , Caulfield Kevin A. , Meesen Raf
Published: April 2023

Noninvasive techniques to record and stimulate the brain rely on passing through the tissues in between the scalp and cortex. Currently, there is no method to obtain detailed information about these scalp-to-cortex distance (SCD) tissues. We introduce GetTissueThickness (GTT), an open-source, automated approach to quantify SCD, and unveil how tissue thicknesses differ across age groups, sexes and brain regions (n = 250). We show that men have larger SCD in lower scalp regions and women have similar-to-larger SCD in regions closer to the vertex, with aging resulting in increased SCD in fronto-central regions. Soft tissue thickness varies by sex and age, with thicker layers and greater age-related decreases in men. Compact and spongy bone thickness also differ across sexes and age groups, with thicker compact bone in women in both age groups and an age-related thickening. Older men generally have the thickest cerebrospinal fluid layer and younger women and men having similar cerebrospinal fluid layers. Aging mostly results in grey matter thinning. Concerning SCD, the whole isn’t greater than the sum of its parts. GTT enables rapid quantification of the SCD tissues. The distinctive sensitivity of noninvasive recording and stimulation modalities to different tissues underscores the relevance of GTT.
Tackling emerging artemisinin resistance by modulating the defensive oxido-reductive mechanism of human malaria parasite by repurposing Nitrofurantoin
Authors: Shafi Sadat , Gupta Sonal , Jain Ravi , Shoaib Rumaisha , Munjal Akshay , Maurya Preeti , Najmi Abul Kalam , Singh Shailja
Published: April 2023

Oxidative stress mediated cell death has remained the prime parasiticidal mechanism of front line anti-malarial, artemisinin (ART). The emergence of resistantPlasmodiumparasites characterized by oxidative stress management due to impaired activation of ART as well as enhanced ROS detoxification has decreased its clinical efficacy. This gap can be filled by development of alternative chemotherapeutic agents to combat resistance defense mechanism. Interestingly, repositioning of clinically approved drugs presents an emerging approach for expediting anti-malarial drug development and resistance management. Herein, we evaluated the anti-malarial potential of Nitrofurantoin (NTF), a clinically used antibacterial drug, against intra-erythrocytic stages of ART-sensitive (Pf3D7) and resistant (PfKelch13R539T) strains ofPlasmodium falciparum(Pf), alone and in combination with ART. NTF exhibited growth inhibitory effect at sub micro molar concentration by arresting parasite growth at trophozoite stage. It also inhibited the survival of resistant parasites as revealed by ring survival assay. Concomitantly,in vitrocombination assay revealed synergistic association of NTF with ART. NTF was found to enhance the reactive oxygen and nitrogen species as well as induced mitochondrial membrane depolarization in parasite. Furthermore, we found that exposure of parasites to NTF disrupted their redox balance by impedingPfGlutathione Reductase activity, which manifests in enhanced oxidative stress, inducing parasite death.In vivoadministration of NTF, alone and in combination with ART inP. berghei ANKA infected mice blocked parasite multiplication and enhanced mean survival time. Overall, our results indicate NTF as a promising repurposable drug with therapeutic potential against drug sensitive as well as resistant parasites.
Playing it safe: information constrains collective betting strategies
Authors: Fleig Philipp , Balasubramanian Vijay
Published: April 2023

Every interaction of a living organism with its environment involves the placement of a bet. Armed with partial knowledge about a stochastic world, the organism must decide its next step or near-term strategy, an act that implicitly or explicitly involves the assumption of a model of the world. Better information about environmental statistics can improve the bet quality, but in practice resources for information gathering are always limited. We argue that theories of optimal inference dictate that “complex” models are harder to infer with bounded information and lead to larger prediction errors. Thus, we propose a principle ofplaying it safewhere, given finite information gathering capacity, biological systems should be biased towards simpler models of the world, and thereby to less risky betting strategies. In the framework of Bayesian inference, we show that there is an optimally safe adaptation strategy determined by the Bayesian prior. We then demonstrate that, in the context of stochastic phenotypic switching by bacteria, implementation of our principle of “playing it safe” increases fitness (population growth rate) of the bacterial collective. We suggest that the principle applies broadly to problems of adaptation, learning and evolution, and illuminates the types of environments in which organisms are able to thrive.