bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differentially Altered Metabolic Pathways in the Amygdala of Subjects with Schizophrenia, Bipolar Disorder and Major Depressive Disorder
Authors: Zhang Xiaolu , Valeri Jake , Eladawi Mahmoud A. , Gisabella Barbara , Garrett Michael R. , Vallender Eric J , McCullumsmith Robert , Pantazopoulos Harry , O’Donovan Sinead M. 
Published: April 2024

AbstractBackground and hypothesisA growing number of studies implicate a key role for metabolic processes in psychiatric disorders. Recent studies suggest that ketogenic diet may be therapeutically effective for subgroups of people with schizophrenia (SCZ), bipolar disorder (BPD) and possibly major depressive disorder (MDD). Despite this promise, there is currently limited information regarding brain energy metabolism pathways across these disorders, limiting our understanding of how brain metabolic pathways are altered and who may benefit from ketogenic diets. We conducted gene expression profiling on the amygdala, a key region involved in in the regulation of mood and appetitive behaviors, to test the hypothesis that amygdala metabolic pathways are differentially altered between these disorders.Study DesignWe used a cohort of subjects diagnosed with SCZ, BPD or MDD, and non-psychiatrically ill control subjects (n=15/group), together with our bioinformatic 3-pod analysis consisting of full transcriptome pathway analysis, targeted pathway analysis, leading-edge gene analysis and iLINCS perturbagen analysis.Study ResultsWe identified differential expression of metabolic pathways in each disorder. Subjects with SCZ displayed downregulation of mitochondrial respiration and nucleotide metabolism pathways. In comparison, we observed upregulation of mitochondrial respiration pathways in subjects with MDD, while subjects with BPD displayed enrichment of pathways involved in carbohydrate metabolism. Several pathways associated with brain metabolism including immune system processes and calcium ion transport were also differentially altered between diagnosis groups.ConclusionOur findings suggest metabolic pathways are differentially altered in the amygdala in these disorders, which may impact approaches for therapeutic strategies.
The novel pathway phenotype “major neurocognitive psychosis” is validated as a distinct class through the analysis of immune-linked neurotoxicity biomarkers and neurocognitive deficits
Authors: Popov Petar , Chen Chen , Al-Hakeim Hussein Kadhem , Al-Musawi Ali Fattah , Al-Dujaili Arafat Hussein , Stoyanov Drozdstoy , Maes Michael 
Published: April 2024

AbstractBackgroundUsing machine learning methods based on neurocognitive deficits and neuroimmune biomarkers, two distinct classes were discovered within schizophrenia patient samples. The first, major neurocognitive psychosis (MNP) was characterized by cognitive deficits in executive functions and memory, higher prevalence of psychomotor retardation, formal thought disorders, mannerisms, psychosis, hostility, excitation, and negative symptoms, and diverse neuroimmune aberrations. Simple neurocognitive psychosis (SNP) was the less severe phenotype.AimsThe study comprised a sample of 40 healthy controls and 90 individuals diagnosed with schizophrenia, divided into MNP and SNP based on previously determined criteria. Soft Independent Modelling of Class Analogy (SIMCA) was performed using neurocognitive test results and measurements of serum M1 macrophage cytokines, IL-17, IL-21, IL-22, and IL-23 as discriminatory/modelling variables. The model-to-model distances between controls and MNP+SNP and between MNP and SNP were computed, and the top discriminatory variables were established.ResultsA notable SIMCA distance of 146.1682 was observed between MNP+SNP and the control group; the top-3 discriminatory variables were lowered motor speed, an activated T helper-17 axis, and lowered working memory. This study successfully differentiated MNP from SNP yielding a SIMCA distance of 19.3. M1 macrophage activation, lowered verbal fluency, and executive functions were the prominent features of MNP versus SNP.DiscussionBased on neurocognitive assessments and the immune-linked neurotoxic IL-6/IL-23/Th-17 axis, we found that MNP and SNP are qualitatively distinct classes. Future biomarker research should always examine biomarkers in the MNP versus SNP phenotypes, rather than in the combined MNP + SNP or schizophrenia group.
Cost-effectiveness analysis of two-way texting (2wT) intervention to improve ART retention among newly-initiated antiretroviral therapy clients in Malawi
Authors: Kiruthu-Kamamia Christine , Weldemariam Hiwot , Chipanda Mirriam , Huwa Jacqueline , Seyani Johnnie , Chirwa Harrison , Kudzala Aubrey , Thawani Agnes , Chintedza Joseph , Sande Odala , Chiwaya Geldert , Tweya Hannock , Pavlova Milena , Groot Wim , Feldacker Caryl 
Published: April 2024

AbstractBackgroundRetention in HIV care is crucial for improved health outcomes. Malawi has a high HIV prevalence and struggles with retention despite significant progress in controlling the epidemic. Mobile health (mHealth) interventions, such as two-way texting (2wT), have shown promise in improving anti-retroviral therapy (ART) retention. We explore the cost-effectiveness of a 2wT intervention in Lighthouse Trust’s Martin Preuss Center (MPC) in Lilongwe, Malawi, that sends automated SMS visit reminders, weekly motivational messages, and supports direct communication between clients and healthcare workers.MethodsCosts and retention rates were compared between 2wT and standard of care (SOC) for 468 clients enrolled in each. Incremental cost-effectiveness ratios (ICERs) were calculated. Scenario analyses were conducted to estimate costs if 2wT expanded.ResultsThe 2wT group had higher retention (80%) than SOC (67%) at 12 months post-ART initiation. For 468 clients, the total annual costs for 2wT were $36,670.38 as compared to SOC costs at $33,458.72, resulting in an ICER of $24,705. Among scenarios, the ICER was -$105,315 if 2wT expanded to all new clients (2678 at MPC and -$723,739 as 2wT expanded to other four high-burden facilities (2901 clients), suggesting high cost savings if 2wT was effectively scaled.ConclusionThe 2wT intervention appears cost-effective to improve ART retention among new ART initiates in a high-burden ART clinic. While mHealth interventions have potential limitations, their benefits in improving patient outcomes and cost savings support their integration into HIV care programs.
Transcriptome-wide identification of 5-methylcytosine by deaminase and reader protein-assisted sequencing
Authors: Zhou Jiale , Zhao Ding , Li Jinze , Kong Deqiang , Li Xiangrui , Zhang Renquan , Liang Yuru , Gao Xun , Qian Yuqiang , Wang Di , Chen Jiahui , Lai Liangxue , Han Yang , Li Zhanjun 
Published: April 2024

Abstract5-Methylcytosine (m5C) is one of the post-transcriptional modifications in mRNA and is involved in the pathogenesis of various diseases. However, the capacity of existing assays for accurately and comprehensively transcriptome-wide m5C mapping still needs improvement. Here, we develop a detection method named DRAM (deaminase and reader protein assisted RNA methylation analysis), in which deaminases (APOBEC1 and TadA-8e) are fused with m5C reader proteins (ALYREF and YBX1) to identify the m5C sites through deamination events neighboring the methylation sites. This antibody-free and bisulfite-free approach provides transcriptome-wide editing regions which are highly overlapped with the publicly available BS-seq datasets and allows for a more stable and comprehensive identification of the m5C loci. In addition, DRAM system even supports ultra-low input RNA (10ng). We anticipate that the DRAM system could pave the way for uncovering further biological functions of m5C modifications.
FGF2 binds to the allosteric site (site 2) and activates integrin αIIbβ3 and FGF1 binds to site 2 but suppresses integrin activation by FGF2: A potential mechanism of anti-thrombotic action of FGF1
Authors: Takada Yoko K , Wu Xueson , Wei David , Hwang Samuel , Takada Yoshikazu 
Published: April 2024

AbstractIt has been believed that platelet integrin αIIbβ3 recognizes fibrinogen and several ECM proteins, and we recently showed that αIIbβ3 binds to several inflammatory cytokines (e.g., CCL5, and CXCL12), which are stored in platelet granules. These ligands bind to the classical ligand (RGD)-binding site (site 1) of integrin αIIbβ3. Also, they bind to the allosteric site (site 2) of αIIbβ3, which is distinct from site 1, and allosterically activate αIIbβ3. Site 2 is known to be involved in allosteric integrin activation and inflammatory signaling. FGF2 is also stored in platelet granules and known to be pro-thrombotic, but it is unclear if FGF2 binds to αIIbβ3. We studied if FGF2 and its homologue FGF1 bind to αIIbβ3 and induce allosteric activation. FGF1 (not stored in platelet granules) is known to be anti-thrombotic. Mechanism of FGF1’s anti-thrombotic action is unknown. Here we describe that FGF1 and FGF2 bound to site 1 of αIIbβ3, indicating that αIIbβ3 is a new receptor for FGF1/2. Notably, FGF2 bound to site 2 and allosterically activated αIIbβ3.Point mutations in the site 2-binding interface of FGF2 suppressed this activation, indicating that FGF2 binding to site 2 is required for activation (FGF2 is an agonist to site 2). In contrast, FGF1 bound to site 2 but did not activate αIIbβ3, and instead suppressed integrin activation induced by FGF2, indicating that FGF1 acts as an antagonist of site 2. A non-mitogenic FGF1 mutant (R50E), which is defective in binding to site 1 of αvβ3, suppressed αIIbβ3 activation by FGF2 as effectively as WT FGF1. We propose that FGF1 R50E has therapeutic potential for anti-thrombosis.
Traumatic life events as predictors for depression in middle-aged men and women: A Finnish twin study
Authors: Maarit Piirtola , Henna Haravuori , Olli Kiviruusu , Satu Viertiö , Jaana Suvisaari , Mauri Marttunen , Jaakko Kaprio , Tellervo Korhonen 
Published: April 2024

ABSTRACTBackgroundWe examined the exposure to adulthood traumatic life events (TLEs) and analysed their associations with depression in women and men. Then we examined whether the associations of TLEs are independent of exposure loading and vulnerability including familial confounding.MethodsTotal of 8410 individuals (45% men, mean age 60 years) participated in the fourth survey of the population-based Finnish Twin Cohort conducted in 2011. Depression was assessed using the Center for Epidemiologic Studies Depression (CES-D) scale (cut-off value ≥20). Participants reported exposure to TLEs during adulthood. Logistic regression adjusted for multiple covariates was used as the individual-based analyses. The effect of shared familial factors was tested using conditional logistic regression in 399 twin pairs discordant for depression.ResultsDepression was more common in women (15%) than in men (11%). Men reported more traffic accidents (men: 11.8%, women: 7.4%), other serious accidents (11.8%, 5.8%), and violent crime (3.1%, 2.0%) whereas women reported more sexual assault (0.7%, 10.6%). Violent crime (Odds Ratio 3.86; 95% Confidence Intervals 2.59, 5.73), sexual assault (3.49; 2.67, 4.55), physical assault (3.10; 2.45, 3.93), and other serious accidents (1.36; 1.01, 1.85) were associated with depression. These associations, except other serious accidents, remained statistically significant after adjusting for multiple covariates including TLEs load and shared familial factors. The associations did not differ by sex.ConclusionsWomen and men differ in exposure to TLEs but, if exposed, they are equally vulnerable for depression. Because traumatic life events are robustly associated with depression, they should be considered in prevention and treatment.
Changes in life expectancy and life span equality during the COVID-19 epidemic in Japan up to 2022
Authors: Okada Yuta , Nishiura Hiroshi 
Published: April 2024

AbstractDemographic analyses enable the evaluation of the impact of COVID-19 on life expectancy. We evaluated the relationship between the life expectancy change from 2020–21 and 2021–22 and COVID-19 epidemic size at prefectural level in Japan. We also conducted age- and cause-specific decomposition of life expectancy change. Trends in life span equality from 2000–22 were evaluated at the national level. Prefectural analysis of 2021–22 life expectancy change and annual per-population COVID-19 cases, person-days in intensive care, and reported COVID-19 deaths showed no significant correlations, unlike our analysis from 2020–21. However, decomposition analysis revealed substantial life expectancy shortening attributable to the population over 35 years old. It also showed large increases in causes of death such as cardiovascular or respiratory disorders as well as COVID-19. Whole-population life span equality declined in 2020 but increased in 2021 and 2022 despite the shorter life expectancy. The discrepancy between life expectancy change and COVID-19 statistics in 2022 suggests the growing ascertainment bias of COVID-19. The increased contribution of cardiovascular disorders to life expectancy shortening is an alarming sign for the future. Life span equality changes in 2021 and 2022 can probably be attributed to increased mortality among older people.
Mechanistic Insights into ASO-RNA Complexation: Advancing Antisense Oligonucleotide Design Strategies
Authors: Hörberg Johanna , Carlesso Antonio , Reymer Anna 
Published: April 2024

ABSTRACTOligonucleotide drugs, an emerging modulator class, hold promise for targeting previously undruggable biomacromolecules. To date, only 18 oligonucleotide drugs, including sought-after antisense oligonucleotides (ASO) and splice-switching oligonucleotides (SSO), have FDA approval. These agents effectively bind mRNA, inducing degradation or modulating splicing. Current oligonucleotide drug design strategies prioritize full Watson-Crick base pair complementarity, overlooking mRNA target 3D shapes. Given that mRNA conformational diversity can impact hybridization, incorporating mRNA key-structural properties into the design may expedite ASO lead discovery. Using atomistic molecular dynamics simulations inspired by experimental data, we demonstrate the advantages of incorporating common triple base pairs into the design of antisense oligonucleotides (ASOs) targeting RNA hairpin motifs, which are highly accessible regions for interactions. By employing an RNA pseudoknot modified into an ASO-hairpin complex, we investigate the effects of ASO length and hairpin loop mutations. Our findings suggest that ASO-mRNA complex stability is influenced by ASO length, number of common triple base pairs, and the dynamic accessibility of bases in the hairpin loop. Our study offers new mechanistic insights into ASO-mRNA complexation and underscores the value of pseudoknots in constructing training datasets for machine learning models aimed at designing novel ASO leads.
Dopamine transients encode reward prediction errors independent of learning rates
Authors: Mah Andrew , Golden Carla E.M. , Constantinople Christine M. 
Published: April 2024

SummaryBiological accounts of reinforcement learning posit that dopamine encodes reward prediction errors (RPEs), which are multiplied by a learning rate to update state or action values. These values are thought to be represented in synaptic weights in the striatum, and updated by dopamine-dependent plasticity, suggesting that dopamine release might reflect the product of the learning rate and RPE. Here, we leveraged the fact that animals learn faster in volatile environments to characterize dopamine encoding of learning rates in the nucleus accumbens core (NAcc). We trained rats on a task with semi-observable states offering different rewards, and rats adjusted how quickly they initiated trials across states using RPEs. Computational modeling and behavioral analyses showed that learning rates were higher following state transitions, and scaled with trial-by-trial changes in beliefs about hidden states, approximating normative Bayesian strategies. Notably, dopamine release in the NAcc encoded RPEs independent of learning rates, suggesting that dopamine-independent mechanisms instantiate dynamic learning rates.
Candidate Denisovan fossils identified through gene regulatory phenotyping
Authors: Mishol Nadav , Herzlinger Gadi , Rak Yoel , Smilanksy Uzy , Carmel Liran , Gokhman David 
Published: April 2024

AbstractDenisovans are an extinct group of humans whose morphology is mostly unknown. The scarcity of verified Denisovan fossils makes it challenging to study their anatomy, and how well they were adapted to their environment. We previously developed a genetic phenotyping approach to gain insight into Denisovan anatomy by detecting gene regulatory changes that likely altered Denisovan skeletal morphology. Here, we scan Middle Pleistocene crania for unclassified or disputed specimens that match predicted Denisovan morphology and thus might be related to Denisovans. We found thatHarbin,Dali, andKabwe 1show a particularly good alignment with the Denisovan profile, with most of their phenotypes matching predicted Denisovan anatomy. We conclude that our genetic phenotyping approach could help classify unidentified specimens, and thatHarbin,Dali, andKabwe 1exhibit a Denisovan-like morphology and could be closely linked to the Denisovan lineage.
Evaluating the effectiveness of the HPV vaccination programme in England, using regression discontinuity design
Authors: Ward Isobel L. , Bermingham Charlotte R. , Soldan Kate , Nafilyan Vahé 
Published: April 2024

AbstractIn England, the National human papillomavirus (HPV) immunisation programme was introduced in 2008 to prevent cervical cancer. Girls aged 12 to 13 were offered routine vaccination, and those aged 14 to 18 years in 2008 were offered ‘catch-up’ vaccination. Using Census 2011, Hospital Episode Statistics and mortality data for the population of England, we exploit the cut-off in eligibility and apply a regression discontinuity design (RDD) to assess the impact of HPV vaccination on cervical disease. Vaccination reduced the incidence of cervical dysplasia and cancer diagnoses by 31% and 75% respectively at ages 23 to 30 years in girls offered catch-up vaccination at ages 17 to 18 years compared to those who were just above the eligibility age for the catch-up vaccination, with a clear discontinuity. Reductions continued amongst girls offered routine vaccination. These estimates obtained with a quasi-experimental approach are similar to vaccine effectiveness estimates based on more traditional approaches. This novel approach provides further evidence of the HPV vaccination programme reducing adverse cervical outcomes in young women and could be used for future studies to evaluate major changes in HPV vaccination policy and for studies of longer-term outcomes including other cancers and deaths.
Statistical mechanics of phenotypic eco-evolution: From adaptive dynamics to complex diversification
Authors: Sireci Matteo , Muñoz Miguel A. 
Published: April 2024

The ecological and evolutionary dynamics of large populations can be addressed theoretically using concepts and methodologies from statistical mechanics. This approach has been extensively discussed in the literature, both within the realm of population genetics, which focuses on genes or “genotypes,” and in adaptive dynamics, which emphasizes traits or “phenotypes.” Following this tradition, here we construct a theoretical framework allowing us to derive “macroscopic” evolutionary equations from a general “microscopic” stochastic dynamics representing the fundamental processes of reproduction, mutation, and selection in a large community of individuals, each one characterized by its phenotypic features. Importantly, in our setup, ecological and evolutionary timescales are intertwined, which makes it particularly suitable to describe microbial communities, a timely topic of utmost relevance. The framework leads to a probabilistic description—even in the case of arbitrarily large populations—of the distribution of individuals in phenotypic space as encoded in what we call the “generalized Crow-Kimura equation” or “generalized replicator-mutator equation.” We discuss the limits in which such an equation reduces to the (deterministic) theory of “adaptive dynamics,” i.e., the standard approach to evolutionary dynamics in phenotypic space. Moreover, we emphasize the aspects of the theory that are beyond the reach of standard adaptive dynamics. In particular, by developing a simple model of a growing and competing population as an illustrative example, we demonstrate that the resulting probability distribution can undergo “dynamical phase transitions.” These transitions may involve shifts from a unimodal distribution to a bimodal distribution, generated by an evolutionary branching event, or to a multimodal distribution through a cascade of evolutionary branching events. Furthermore, our formalism allows us to rationalize these cascades using the parsimonious approach of Landau's theory of phase transitions. Finally, we extend the theory to account for finite populations and illustrate the possible consequences of the resulting stochastic or “demographic” effects. Altogether, the present framework extends and/or complements existing approaches to evolutionary and adaptive dynamics and paves the way to more systematic studies of microbial communities as well as to future developments including theoretical analyses of the evolutionary process from the general perspective of nonequilibrium statistical mechanics.

Published by the American Physical Society
2024
Trust building in the sharing economy: proposition and test of an integrated model
Authors: Fernandes Bruno , Nogueira Roberto , Chimenti Paula 
Published: April 2024

Purpose
The purpose of this study is to propose and test an integrated model to explain how trust is built in sharing economy (SE) transactions.

Design/methodology/approach
Initially, prior literature was systematically selected and synthesized to develop a comprehensive framework applicable to multiple trust-building perspectives and categories of SE platforms. Then, a survey was conducted to validate the constructs and test the model with Airbnb guests. A sample of 351 responses was collected and analyzed using structural equation modeling.

Findings
The results indicate that the cues an individual assesses to infer their counterpart’s trustworthiness and the reasons the individual has for engaging in the SE transaction can explain a large variance in their trust in the counterpart. In addition, the individual’s propensity to trust moderates this relationship.

Research limitations/implications
The proposed model can help identify the most effective trust-building mechanisms. It can be taken as a common knowledge base for scholars to compare the four trust-building perspectives and different categories of SE platforms, as well as to investigate the subject over time and across cultures.

Practical implications
This research can also help practitioners understand the complexity of building trust and design platform features to do so.

Social implications
A unified model clarifies trust in the SE, aiding platform growth and community bonding. This insight guides platforms in feature enhancement and policymakers in drafting balanced regulations.

Originality/value
To the best of the authors’ knowledge, for the first time, there is a comprehensive and parsimonious model applicable to the four trust-building perspectives and different categories of SE platforms.