bluuebunny/crossref_metadata_2025_split huggingface dataset:
Converging effects of cannabis and psychosis on the dopamine system: A longitudinal neuromelanin-sensitive MRI study in cannabis use disorder and first episode schizophrenia
Authors: Ahrens Jessica , Ford Sabrina D. , Schaefer Betsy , Reese David , Khan Ali R. , Tibbo Philip , Rabin Rachel , Cassidy Clifford , Palaniyappan Lena 
Published: September 2024

AbstractImportanceDespite evidence that individuals who use cannabis early in life are at elevated risk of psychosis and that the neurotransmitter dopamine has a role in both conditions, the mechanism linking the two conditions remains unclear.ObjectiveTo use neuromelanin-sensitive MRI (neuromelanin-MRI), a practical, proxy measure of dopamine function, to assess whether a common alteration in the dopamine system may be implicated in cannabis use and psychosis and whether this alteration can be observed in cannabis users whether or not they have a diagnosis of first-episode schizophrenia.Design, Setting, and ParticipantsThis longitudinal observational study recruited participants from 2019 to 2023 from an early intervention service for psychosis in London, Ontario, Canada. The sample consisted of 25 participants with cannabis use disorder (CUD) and 36 participants without CUD (nCUD), of which 28 had first-episode schizophrenia (FES). One-year follow-up was completed for 12 CUD and 25 nCUD participants.Main Outcomes and MeasuresNeuromelanin-MRI contrast within the substantia nigra (SN) and within a subregion previously linked to psychosis severity (a priori psychosis region of interest) and diagnoses of schizophrenia-spectrum disorder and cannabis use disorder derived from the Structured Clinical Interview for DSM-5. Linear mixed effects analyses were performed relating neuromelanin-MRI contrast to clinical measures.ResultsWe found that CUD was associated with elevated neuromelanin-MRI signal in a cluster of ventral SN voxels (387 of 2060 SN voxels, pcorrected=0.027, permutation test). Furthermore, CUD was associated with elevated neuromelanin-MRI signal in an SN subregion previously documented to have elevated signal in relation to untreated psychotic symptoms (t92=2.12, p=0.037). In contrast, FES was not associated with a significant alteration in neuromelanin-MRI signal (241 SN voxels had elevated signal, pcorrected=0.094).Conclusions and RelevanceThese findings suggest that elevated dopamine function in a critical SN subregion may contribute to the risk of psychosis in people with CUD. Thus, cannabis affects the long-suspected ‘final common pathway’ for the clinical expression of psychotic symptoms. Imaging the dopamine system with neuromelanin-MRI may index long-term dopamine turnover.Key PointsQuestionIs the same midbrain dopamine pathway impacted by cannabis as in psychosis?FindingsCannabis use disorder participants had elevated neuromelanin-MRI signal in a cluster of ventral substantia nigra voxels and in a subregion previously documented to have elevated signal in relation to untreated psychotic symptoms.MeaningIncreased dopamine functioning in the ventral substantia nigra may contribute to the risk of psychosis in people with cannabis use disorders.
G-CSF and IL-6 drive myeloid dysregulation during severe viral infection
Authors: Kajihara Kimberly , Yan Donghong , Seim Gretchen L. , Little-Hooy Hannah , Kang Jing , Chen Cynthia , De Simone Marco , Delemarre Tim , Darmanis Spyros , Shivram Haridha , Bauer Rebecca N. , Rosenberger Carrie M. , Kapadia Sharookh B. , Xu Min , Reyes Miguel 
Published: September 2024

ABSTRACTDysregulated myeloid states are associated with disease severity in both sepsis and COVID-19. However, their relevance in non-COVID-19 viral infection, the factors driving their induction, and their role in tissue injury remain poorly understood. We performed a meta-analysis of 1,622,180 myeloid cells from 890 COVID-19 or sepsis patients and controls across 19 published blood scRNA-seq datasets, which revealed severity-associated gene programs in both neutrophils and monocytes pointing to emergency myelopoiesis (EM). Using published bulk transcriptional data from 562 individuals with non-COVID-19 viral disease, we show that these signatures are similarly upregulated during severe influenza and RSV infection. Analysis of transcriptional and proteomic responses in tocilizumab-treated COVID-19 patients show that IL-6 signaling blockade results in a partial reduction of EM signatures and a compensatory increase in the growth factor G-CSF. Using a cellular model of human myelopoiesis, we show that both IL-6 and G-CSF stimulate the production of myeloid cells that express EM signaturesin vitro. Using a mouse model of severe influenza infection, we demonstrate the effect of IL-6 and G-CSF signaling blockade on EM-associated myeloid cells, and highlight the opposing effects of EM-induced neutrophils and monocytes on tissue injury. Our study demonstrates the link between systemic cytokines and myeloid dysregulation during severe infection in humans, and highlights the cooperative role of IL-6 and G-CSF signaling in driving infection-induced myelopoiesis.
Bacterial genome encoded ParMs
Authors: Ali Samson , Koh Adrian , Popp David , Tanaka Kotaro , Kitaoku Yoshihito , Miyazaki Naoyuki , Iwasaki Kenji , Mitsuoka Kaoru , Robinson Robert C. , Narita Akihiro 
Published: September 2024

AbstractParMs generally exist on low copy number plasmids where they contribute to plasmid segregation and stable inheritance. We carried out bioinformatics analysis, which indicated that ParM genes are not only confined to plasmids but are also occasionally found on genomes. Here we report the discovery and characterization of two chromosome encoded ParMs (cParMs) from the genomes of Desulfitobacterium hafniense (Dh-cParM1) and Clostridium botulinum (Cb-cParM). Both cParMs form filaments, exhibit nucleotide hydrolysis, and possess characteristic ParM subunit structures. Dh-cParM1 forms single and tightly coupled double filaments and is highly conserved on the chromosomes of five of six Desulfitobacterium species. Interestingly, these bacteria have not been reported to harbour plasmids. Cb-cParM possesses unique properties. Its filaments were stable after nucleotide hydrolysis and Pi release, and its ParR, (Cb-cParR) did not affect the initial stage of Cb-cParM polymerization but displayed properties of a depolymerization factor for mature filaments. These results indicate functional, polymerizing ParMs can be encoded on genomes, suggesting that ParM roles may extend to other functions beyond plasmid segregation.
Effects of Health Technology Use and Digital Health Engagement on Clinical Trial Participation: Findings from the Health Information National Trends Survey
Authors: Peiper Nicholas C. , Furmanek Stephen , McCants Kelly , Brown Edward H. 
Published: September 2024

AbstractBackgroundClinical trials are critical to scientific advances and medical progress, although awareness and participation remain low in the general population. The existing literature indicates that clinical trial knowledge and participation is multifactorial. Yet, little is known about the association between clinical trial participation with health technology use and digital health engagement to search for health information, interact with medical providers, and seek health supports.ObjectiveExamine the multivariate association between clinical trial knowledge and participation with past-year health technology use and digital health engagement with medical providers.DesignCross-sectional data from a federal surveillance system.ParticipantsA total of 3,865 US adult respondents from the Health Information National Trends Survey 5, Cycle 4 conducted in 2020.Main MeasuresThe two outcomes were clinical trial knowledge (no knowledge, a little knowledge, a lot of knowledge) and participation (never invited, invited did not participate, invited and participated). There were four binary indicators of health technology use for the following purposes in the past year: searching for health or medical information, communicating with a doctor’s office, looking up medical test results, and making medical appointments. There were four binary indicators of digital health engagement in the past year: sharing health information on social media, participating in a health forum or support group, watching health-related videos on YouTube, and awareness of ClinicalTrials.gov.Key ResultsSurvey-weighted multivariate regression models demonstrated that awareness of ClinicalTrials.gov had the largest associations with clinical trial knowledge and participation. Digital technology use to engage with medical providers and electronic health records was associated with clinical participation, although the vast majority of respondents had never been invited.ConclusionsFindings from this study can inform the design of large-scale digital health campaigns and quality improvement programs focused on increasing clinical trial participation.
Neural emotion regulation during pregnancy – a fMRI study investigating a transdiagnostic mental health factor in healthy first-time pregnant women
Authors: Weinmar Franziska , Kogler Lydia , Rehbein Elisa , Morawetz Carmen , Sundström-Poromaa Inger , Skalkidou Alkistis , Derntl Birgit 
Published: September 2024

AbstractPregnancy is a psycho-neuro-endocrinological transition phase in which a plethora of hormone levels rise substantially, modulating socioemotional functions, brain structures, and networks and thus presenting a window of vulnerability for mental health. A transdiagnostic factor for psychopathology is emotion regulation, which is influenced by sex hormones, such as estradiol (E2), across the menstrual cycle on the behavioral and neural level. Whether this is also the case in the antepartum period remains unknown. For the first time, behavioral and neural emotion regulation were investigated in healthy primiparous pregnant females with extremely high E2 levels during the second trimester (N = 15) using a functional magnetic resonance imaging (fMRI) paradigm. Results were compared with naturally-cycling females with high E2 levels (after E2-administration, N = 16) and low E2 levels (early follicular phase, N = 16). Although pregnant females reported the lowest trait use of cognitive reappraisal, all females successfully regulated their emotions by applying cognitive reappraisal in the scanner. On the neural level, all females had increased activity in the left middle frontal gyrus during downregulation of negative emotions. Pregnant females showed no significant differences in functional connectivity (psychophysiological interaction, resting-state) related to emotion regulation compared to the nonpregnant group. However, group differences emerged for amygdala activation. In pregnant females, increased amygdala activity predicted reduced regulation success and was positively associated with depression scores. This first fMRI study during pregnancy indicates that depression scores are reflected in heightened amygdala activity already observable in the antepartum period. Thus, through its association with reduced regulation success, increased amygdala activity suggests a neural risk marker for peripartum mental health. Future research needs to investigate emotion regulation in pregnant and postpartum women to further understand pregnancy-related changes and associations of mood, emotional and neural functions. Eventually, this will allow enhanced identification, prevention, and treatment of peri- and postpartum mental ill-health.
Improved resolution of influenza vaccination responses with high-throughput live virus microneutralisation
Authors: Adams Lorin , Stevenson-Leggett Phoebe , Le Lee Jia , Bazire James , Dowgier Giulia , Hobbs Agnieszka , Roustan Chloë , Borg Annabel , Carr Christine , Innocentin Silvia , Webb Louise MC , Smith Callie , Bawumia Philip , Lewis Nicola , O’Reilly Nicola , Kjaer Svend , Linterman Michelle A , Harvey Ruth , Wu Mary Y , Carr Edward J 
Published: September 2024

AbstractInfluenza remains a significant threat to human and animal health. Assessing serological protection against influenza has relied upon haemagglutinin inhibition assays, which are used to gauge existing immune landscapes, seasonal vaccine decisions and in systems vaccinology studies. Here, we adapt our high-throughput live virus microneutralisation assay for SARS-CoV-2, benchmark against haemagglutinin inhibition assays, and report serological vaccine responsiveness in a cohort of older (>65yo) community dwelling adults (n=73), after the adjuvanted 2021-22 Northern Hemisphere quadrivalent vaccine. We performed both assays against all four viruses represented in the vaccine (A/Cambodia/H3N2/2020, A/H1pdm/Victoria/2570/2019, B/Yamagata/Phuket/2013, BVIC/Washington/02/201), using sera drawn on days 0 [range: d-28 to d0], 7 [d6-10] and 182 [d161-196] with respect to vaccination. We found population-level concordance between the two assays (Spearman’s correlation coefficient range 0.48-0.88; all P≤1.4 × 10−5). The improved granularity of microneutralisation was better able to estimate fold-changes of responses, and quantify the inhibitory effect of pre-existing antibody. Our high-throughput method offers an alternative approach to assess influenza-specific serological responses with improved resolution.
Machine Learning Insights into HLA Noncoding Sequence Mismatches and Their Impact on DPB1 Matching in Hematopoietic Cell Transplantation
Authors: Askar Medhat , Mosbruger Timothy L. , Shaw Grace Tzun-Wen , Kim Haedong , Duan Yuncheng , Allen Andrew S. , Duke Jamie L. , Olson Timothy S. , Monos Dimitri S. , Hayeck Tristan J. 
Published: September 2024

PurposeHCT is vital for treating hematological malignancies, relying on HLA matching between unrelated patient-donor pairs to significantly reduce adverse outcomes. Recent studies recognize the potential impact of HLA-DPB1 mismatches on HCT outcomes. Multiple approaches focus on finding better-tolerated HLA-DPB1 mismatches. Additionally, recent studies suggest matching at noncoding HLA sequence may improve HCT outcomes. This study aims to evaluate different approaches for categorizing DPB1 mismatches in patient-donor pairs and explore the potential impact of noncoding mismatches (available in class I HLA genes) on clinical outcomes.MethodsA retrospective study of 5,106 HCT pairs using Cox proportional hazards models, weighted by a machine learning algorithm, evaluates the impact of particular combinations of HLA-DPB1 mismatches in the context of noncoding HLA class I mismatches on outcomes of HCT. HLA-DPB1 mismatch criteria included T-cell epitope permissive/non-permissive mismatches, expression markers, and evolutionary clade mismatches.ResultsTwo HLA-DPB1 mismatches, using multiple criteria, lead to significant hazards of acute graft versus host disease grades 2-4, in the T cell replete group. When HLA-DPB1 mismatches occurred across evolutionary clades (DP2 allele/low-expression patient vs DP5 allele/high-expression in the donor), the deplete group showed significant hazards for treatment-related mortality (TRM) (HR=1.94, p-value=8.9×10-7) and overall survival (OS) (HR=1.67, p-value=1.3×10-5) for additive effects of noncoding mismatches with two HLA-DPB1 mismatches.ConclusionTwo HLA-DPB1 mismatches remain to predict worse outcomes. However, noncoding mismatches in HLA class I genes confer elevated hazards of TRM and OS in conjunction with mismatches across evolutionary branches of HLA-DPB1. Therefore, noncoding mismatches may inform donor selection in the presence of HLA-DPB1 mismatches and improve HCT outcomes, emphasizing the utility of comprehensive sequencing of HLA alleles in HCT settings.
Comparing the test performance of dried-blood-spot and plasma HIV recent infection testing samples in a nationally scaled sex worker programme in Zimbabwe
Authors: Rice Brian D , Jones Harriet S , Machingura Fortunate , Gaihai Leah , Makamba Memory , Chanyowedza Thomas , Masvikeni Panganai , Matsikire Edward , Matambanadzo Primrose , Musemburi Sithembile , Chida Phillip N , Dirawo Jeffery , Mugurungi Owen , Bourdin Sarah , Hargreaves James R , Murphy Gary , Cowan Frances M 
Published: September 2024

AbstractRecency testing can provide strategic insights as to whether a person newly diagnosed with HIV recently acquired their infection or not. To understand potential biases associated with HIV recency testing, we explored the extent sample type influences whether a person is assigned as being recent. Implementing a laboratory-based Recent Infection Testing Algorithm (RITA) across the Centre for Sexual Health and HIV/AIDS Research (CeSHHAR) key populations programme in Zimbabwe between October 2021 and January 2023, we compared plasma-based and dried-bloodspot (DBS) HIV recency samples. Over the study period, 24,976 individual female sex workers HIV tested, of whom 9.5% (2,363/24,979) newly tested HIV positive. Of these 2,363 women, 55.5% (1311/2,363) were offered and gave consent for a sample to be taken for DBS recency and viral load testing, among whom 11.7% (153/1,311) were classified as having a recent infection. A subset of 464 women were offered and consented to paired sample collection, among whom 10.1% (47) and 12.3% (57) of plasma and DBS samples, respectively, were classified as recent. Overall, categorical determination was good, with 97% of results concordant. Of 58 women with paired sample collection who had a test result classified as recent, 46 (79.3%) were concordant recent on both DBS and plasma, with 12 (20.7%) being dis-concordant. Of these 12 women’s samples, 11 were deemed long-standing by the plasma assay but recent by the paired DBS, and one deemed long-standing by DBS but recent by the paired plasma sample. Depending on use-case and setting, there are trade-offs when considering DBS or plasma-based samples between test performance and ease of implementation. Our data can help inform statistical adjustments to harmonise cut-offs on DBS and plasma assays, thereby improving the use and interpretation of recency assays in population-level HIV surveillance activities.
Lipoprotein (a) is associated with increased risk of Abdominal Aortic Aneurysm
Authors: Sharma Pranav , Judy Renae , Yuan Shuai , Gellatly Corry , Saxby Katie L. , Bown Matthew J. , Levin Michael G. , Damrauer Scott M. 
Published: September 2024

ABSTRACTIntroductionLipoprotein(a) (Lp(a)) is a circulating apolipoprotein B (ApoB) containing particle that has been observationally linked to atherosclerotic cardiovascular disease and is the target of emerging therapeutics. Recent work has highlighted the role of circulating lipoproteins in abdominal aortic aneurysm (AAA). We sought to triangulate human observational and genetic evidence to evaluate the role of Lp(a) in AAA.MethodsWe tested the association between circulating levels of Lp(a) and clinically diagnosed abdominal aortic aneurysms while controlling for traditional AAA risk factors and levels of ApoB using logistic regression among 795 individuals with and 374,772 individuals without AAA in the UK Biobank (UKB). Multivariable Mendelian randomization (MVMR) was used to test for putatively causal associations between Lp(a) and AAA controlling for ApoB. Genetic instruments for Lp(a) and ApoB were created from genome-wide association studies (GWAS) of Lp(a) and ApoB comprising 335,796 and 418,505 UKB participants, respectively. The instruments were tested for association with AAA using data from a GWAS of 39,221 individuals with and 1,086,107 without AAA.ResultsElevated Lp(a) levels were observationally associated with an increased risk of AAA (OR 1.04 per 10 nmol/L Lp(a); 95%CI 1.02-1.05; P<0.01). Clinically elevated Lp(a) levels (>150nmol/L) were likewise associated with an increased risk of AAA (OR 1.47; 95% CI 1.15-1.88; P < 0.01) when compared to individuals with Lp(a) levels <150nmol/L. MVMR confirmed a significant, ApoB-independent association between increased Lp(a) and increased risk of AAA (OR 1.13 per SD increase in Lp(a); 95%CI 1.02-1.24; P<0.02).ConclusionBoth observational and genetic analyses support an association between increased Lp(a) and AAA risk that is independent of ApoB. These findings suggest that Lp(a) may be a therapeutic target for AAA and drive the inclusion of AAA as an outcome in clinical trials of Lp(a) antagonists.
Cohort profile: The Camden Study – a pregnancy cohort study of pregnancy complications and birth outcomes in Camden, New Jersey, USA
Authors: Shiau Stephanie , Chen Xinhua , April-Sanders Ayana , Francis Ellen C. , Rawal Shristi , Hansel Megan , Adeyemi Kehinde , Rivera-Núñez Zorimar , Barrett Emily S. 
Published: September 2024

AbstractBackgroundPregnancy is a unique stage of the life course characterized by trade-offs between the nutritional, immune, and metabolic needs of the mother and fetus. The Camden Study was originally initiated to examine nutritional status, growth, and birth outcomes in adolescent pregnancies and expanded to study dietary and molecular predictors of pregnancy complications and birth outcomes in young women.MethodsFrom 1985-2006, 4765 pregnant participants aged 12 years and older were recruited from Camden, NJ, one of the poorest cities in the U.S. The cohort reflects a population under-represented in perinatal cohort studies (45% Hispanic, 38% non-Hispanic Black, 17% White participants; 98% using Medicaid in pregnancy). Study visits, including questionnaires, dietary assessments, and biospecimen collection, occurred in early and late pregnancy as well as at delivery. Medical records were abstracted, and a subset of mothers and infants participated in a six-week postpartum visit.ResultsOver the last five decades, the Camden Study has provided data toward the publication of numerous peer-reviewed papers. Results show that adolescent linear growth in pregnancy is associated with smaller birth size, possibly due to impaired hemodynamics. In the context of preterm birth and other perinatal outcomes, analyses of nutritional data have demonstrated the importance of micronutrients (e.g., folate, iron, zinc), as well as glucose/insulin dynamics and prenatal supplement use. More recent analyses have begun to unpack the biochemical pathways in pregnancy that may be shaped by race as an indicator for systemic racism.ConclusionsThe Camden Study data and biorepositories are well-positioned to support future research aimed at better understanding perinatal health in under-represented women and infants. Linkages to subsequent health and administrative records and the potential for recontacting participants over 18-39 years after initial participation may provide key insights into the trajectories of maternal and child health across the life course.