bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing regional intracortical myelination in schizophrenia spectrum and bipolar disorders using the optimized T1w/T2w-ratio
Authors: Jørgensen Kjetil Nordbø , Nerland Stener , Slapø Nora Berz , Norbom Linn B. , Mørch-Johnsen Lynn , Wortinger Laura Anne , Barth Claudia , Andreou Dimitrios , Maximov Ivan I. , Geier Oliver M. , Andreassen Ole A. , Jönsson Erik G. , Agartz Ingrid
Published: June 2023

Background

Dysmyelination could be part of the pathophysiology of schizophrenia spectrum (SCZ) and bipolar disorders (BPD), yet few studies have examined myelination of the cerebral cortex. The ratio of T1- and T2-weighted magnetic resonance images (MRI) correlates with intracortical myelin. We investigated the T1w/T2w-ratio and its age trajectories in patients and healthy controls (CTR) and explored associations with antipsychotic medication use and psychotic symptoms.

Methods

Patients with SCZ (n=64; mean age = 30.4 years, SD=9.8), BPD (n=91; mean age 31.0 years, SD=10.2), and CTR (n=155; mean age = 31.9 years, SD=9.1) who participated in the TOP study (NORMENT, University of Oslo, Norway) were clinically assessed and scanned using a General Electric 3T MRI system. T1w/T2w-ratio images were computed using an optimized pipeline with intensity normalization and field inhomogeneity correction. Vertex-wise regression models were used to compare groups and examine group × age interactions. In regions showing significant differences, we explored associations with antipsychotic medication use and psychotic symptoms.

Results

No main effect of diagnosis was found. However, age slopes of the T1w/T2w-ratio differed significantly between SCZ and CTR, predominantly in frontal and temporal lobe regions: Lower T1w/T2w-ratio values with higher age were found in CTR, but not in SCZ. Follow-up analyses revealed a more positive age slope in patients who were using antipsychotics and patients using higher chlorpromazine-equivalent doses.

Conclusions

While we found no evidence of reduced intracortical myelin in SCZ or BPD relative to CTR, different regional age trajectories in SCZ may suggest a promyelinating effect of antipsychotic medication.
Causal Interactions in Brain Networks Predict Pain Levels in Trigeminal Neuralgia
Authors: Liang Yun , Zhao Qing , Neubert John K. , Ding Mingzhou
Published: June 2023

Trigeminal neuralgia (TN) is a highly debilitating facial pain condition. Magnetic resonance imaging (MRI) is the main method for generating insights into the central mechanisms of TN pain in humans. Studies have found both structural and functional abnormalities in various brain structures in TN patients as compared with healthy controls. Whereas studies have also examined aberrations in brain networks in TN, no studies have to date investigated causal interactions in these brain networks and related these causal interactions to the levels of TN pain. We recorded fMRI data from 39 TN patients who either rested comfortably in the scanner during the resting state session or tracked their pain levels during the pain tracking session. Applying Granger causality to analyze the data and requiring consistent findings across the two scanning sessions, we found 5 causal interactions, including: (1) Thalamus → dACC, (2) Caudate → Inferior temporal gyrus, (3) Precentral gyrus → Inferior temporal gyrus, (4) Supramarginal gyrus → Inferior temporal gyrus, and (5) Bankssts → Inferior temporal gyrus, that were consistently associated with the levels of pain experienced by the patients. Utilizing these 5 causal interactions as predictor variables and the pain score as the predicted variable in a linear multiple regression model, we found that in both pain tracking and resting state sessions, the model was able to explain ∼36% of the variance in pain levels, and importantly, the model trained on the 5 causal interaction values from one session was able to predict pain levels using the 5 causal interaction values from the other session, thereby cross-validating the models. These results, obtained by applying novel analytical methods to neuroimaging data, provide important insights into the pathophysiology of TN and could inform future studies aimed at developing innovative therapies for treating TN.
Combined GWAS and single cell transcriptomics uncover the underlying genes and cell types in disorders of gut-brain interaction
Authors: Majd Alireza , Richter Mikayla N , Samuel Ryan M , Cesiulis Andrius , Ghazizadeh Zaniar , Wang Jeffrey , Fattahi Faranak
Published: June 2023

Disorders of gut-brain interaction (DGBIs), formerly known as functional gastrointestinal disorders, are extremely common and historically difficult to manage. This is largely because their cellular and molecular mechanisms have remained poorly understood and understudied. One approach to unravel the molecular underpinnings of complex disorders such as DGBIs is performing genome wide association studies (GWASs). However, due to the heterogenous and non-specific nature of GI symptoms, it has been difficult to accurately classify cases and controls. Thus, to perform reliable studies, we need to access large patient populations which has been difficult to date. Here, we leveraged the UK Biobank (UKBB) database, containing genetic and medical record data of over half a million individuals, to perform GWAS for five DGBI categories: functional chest pain, functional diarrhea, functional dyspepsia, functional dysphagia, and functional fecal incontinence. By applying strict inclusion and exclusion criteria, we resolved patient populations and identified genes significantly associated with each condition. Leveraging multiple human single-cell RNA-sequencing datasets, we found that the disease associated genes were highly expressed in enteric neurons, which innervate and control GI functions. Further expression and association testing-based analyses revealed specific enteric neuron subtypes consistently linked with each DGBI. Furthermore, protein-protein interaction analysis of each of the disease associated genes revealed protein networks specific to each DGBI, including hedgehog signaling for functional chest pain and neuronal function and neurotransmission for functional diarrhea and functional dyspepsia. Finally, through retrospective medical record analysis we found that drugs that inhibit these networks are associated with an increased disease risk, including serine/threonine kinase 32B drugs for functional chest pain, solute carrier organic anion transporter family member 4C1, mitogen-activated protein kinase 6, and dual serine/threonine and tyrosine protein kinase drugs for functional dyspepsia, and serotonin transporter drugs for functional diarrhea. This study presents a robust strategy for uncovering the tissues, cell types, and genes involved in DGBIs, presenting novel predictions of the mechanisms underlying these historically intractable and poorly understood diseases.
Hypertension diagnosis, treatment, and control in India: nationally representative results from 1.69 million adults, 2019-2021
Authors: Varghese Jithin Sam , Venkateshmurthy Nikhil Srinivasapura , Sudharsanan Nikkil , Jeemon Panniyammakal , Patel Shivani A , Thirumurthy Harsha , Roy Ambuj , Tandon Nikhil , Narayan KM Venkat , Prabhakaran Dorairaj , Ali Mohammed K.
Published: June 2023

Background

Hypertension is a major cause of morbidity and mortality worldwide. Previous efforts to characterize gaps in the hypertension care continuum in India –including diagnosis, treatment, and control– did not assess district level variation. Local data are critical for planning, implementation, and monitoring efforts to curb hypertension burdens. Our objective is to characterize the hypertension care continuum in India among individuals aged 18-98 years old at national, state, and district levels and by socio-demographic group.

Methods

Data were from 1,895,297 individuals in the nationally representative Fifth National Family Health Survey (NFHS-5), 2019-21. Hypertension was defined as self-reported diagnosis or newly measured blood pressure ≥140/90 mmHg. Among those with hypertension, we calculated the proportion diagnosed (self-reported). Among those with diagnosed hypertension, we computed the proportion treated (self-reported medication use). Among those treated, we calculated the proportion controlled (BP <140/90 mmHg [20-80 years] or <150/90 mmHg [>80 years]) based on national guidelines. Estimates were also provided among the total with hypertension. To assess differences in the care continuum between or within states (i.e. between districts), we partitioned the variance at both levels using linear mixed models.

Results

Among 1,691,109 adult respondents nationally (52.6% female; mean age: 41.6 years), 28.2% [95%CI: 28.0-28.4] had hypertension, of whom, 36.7% [36.3-37.2] were diagnosed. Among those diagnosed, 44.7% [44.1-45.3] reported taking medication (17.7% [17.5-17.9] of total with hypertension). Among those treated, 52.3% [51.4-53.1] had blood pressure control (9.1% [8.9-9.2] of total with hypertension). There were substantial variations across districts in diagnosis [range: 6.3–77.5%], treatment [8.7–97.1%] and control [2.7–76.6%]. Notably, large proportions of the variation in hypertension diagnosis (53.7%), treatment (32.8%), and control (57.7%) were within states, not just between states.

Conclusions

In India, more than 1 in 4 people have hypertension, and of these, only 1 in 3 are diagnosed, less than 1 in 5 are treated, and only 1 in 11 controlled. National averages hide considerable state- and district-level variation in the care continuum, implying the need for targeted, decentralized solutions to improve the hypertension care continuum in India.
Dynamic phytomeric growth contributes to local adaptation in barley
Authors: Huang Yongyu , Maurer Andreas , Giehl Ricardo F. H. , Zhao Shuangshuang , Golan Guy , Thirulogachandar Venkatasubbu , Li Guoliang , Zhao Yusheng , Trautewig Corinna , Himmelbach Axel , Börner Andreas , Jayakodi Murukarthick , Stein Nils , Mascher Martin , Pillen Klaus , Schnurbusch Thorsten
Published: June 2023

Vascular plants segment their body axis with iterative nodes of lateral branches and internodes. Appropriate node initiation and internode elongation are fundamental to plant fitness and crop yield formation; but how they are spatiotemporally coordinated remains elusive. We show that in barley (Hordeum vulgareL.), selections under domestication have extended the apical meristematic phase to promote node initiation, but constrained subsequent internode elongation. In both vegetative and reproductive axes, internode elongation displays a dynamic proximal – distal gradient, and among subpopulations of domesticated barleys at the global range, node initiation and proximal internode elongation are associated with latitudinal and longitudinal gradients, respectively. Genetic and functional analysis suggest that, in addition to their converging roles in node initiation, flowering time genes are repurposed to specify the dynamic internode elongation. Our study provides an integrated view of barley node initiation and internode elongation, and suggests that plant architecture has to be recognized as dynamic phytomeric units in the context of crop evolution.
LORA, Lipid Over-Representation Analysis based on structural information
Authors: Vondrackova Michaela , Kopczynski Dominik , Hoffmann Nils , Kuda Ondrej
Published: June 2023

With the increasing number of lipidomic studies, there is a need for efficient and automated analysis of lipidomic data. One of the challenges faced by most existing approaches to lipidomic data analysis is lipid nomenclature. The systematic nomenclature of lipids contains all available information about the molecule, including its hierarchical representation, which can be used for statistical evaluation. The Lipid Over-Representation Analysis (LORA) web application (https://lora.metabolomics.fgu.cas.cz) analyzes this information using the Java-based Goslin framework, which translates lipid names into a standardized nomenclature. Goslin provides the level of lipid hierarchy, including information on headgroups, acyl chains, and their modifications, up to the ‘complete structure’ level. LORA allows the user to upload the experimental query and universe datasets, select a grammar for lipid name normalization, and then process the data. The user can then interactively explore the results and perform lipid overrepresentation analysis based on selected criteria. The results are graphically visualized according to the lipidome hierarchy. The lipids present in the most over-represented terms (lipids with the highest number of enriched shared structural features) are defined as Very Important Lipids (VILs). For example, the main result of a demo dataset is the information that the query is significantly enriched with ‘glycerophospholipids’ containing ‘acyl 20:4’ at ‘sn-2 position’. These terms define a set of VILs (e.g., PC 18:2/20:4;O and PE 16:0/20:4(5,8,10,14);OH). All results, graphs, and visualizations are summarized in a report. LORA is a tool focused on the smart mining of epilipidomics datasets to facilitate their interpretation at the molecular level.
Parallelized Acquisition of Orbitrap and Astral Analyzers Enables High-Throughput Quantitative Analysis
Authors: Stewart Hamish , Grinfeld Dmitry , Giannakopulos Anastassios , Petzoldt Johannes , Shanley Toby , Garland Matthew , Denisov Eduard , Peterson Amelia , Damoc Eugen , Zeller Martin , Arrey Tabiwang N. , Pashkova Anna , Renuse Santosh , Hakimi Amirmansoor , Kühn Andreas , Biel Matthias , Kreutzmann Arne , Hagedorn Bernd , Colonius Immo , Schütz Adrian , Stefes Arne , Dwivedi Ankit , Mourad Daniel , Hoek Max , Reitemeier Bastian , Cochems Philipp , Kholomeev Alexander , Ostermann Robert , Quiring Gregor , Ochmann Maximilian , Möhring Sascha , Wagner Alexander , Petker André , Kanngiesser Sebastian , Wiedemeyer Michael , Balschun Wilko , Hermanson Daniel , Zabrouskov Vlad , Makarov Alexander , Hock Christian
Published: June 2023

The growing trend towards high-throughput proteomics demands rapid liquid chromatography-mass spectrometry (LC-MS) cycles that limit the available time to gather the large numbers of MS/MS fragmentation spectra required for identification. Orbitrap analyzers scale performance with acquisition time, and necessarily sacrifice sensitivity and resolving power to deliver higher acquisition rates. We developed a new mass spectrometer that combines a mass resolving quadrupole, the Orbitrap and the novel Asymmetric Track Lossless (Astral) analyzer. The new hybrid instrument enables faster acquisition of high-resolution accurate mass (HRAM) MS/MS spectra compared to state-of-the-art mass spectrometers. Accordingly, new proteomics methods were developed that leverage the strengths of each HRAM analyzer, whereby the Orbitrap analyzer performs full scans with high dynamic range and resolution, synchronized with Astral analyzer’s acquisition of fast and sensitive HRAM MS/MS scans. Substantial improvements are demonstrated over previous methods using current state-of-the-art mass spectrometers.

Abstract Figure
The PMA Phorbol Ester Tumor Promoter Increases Canonical Wnt Signaling Via Macropinocytosis
Authors: Tejeda-Muñoz Nydia , Azbazdar Yagmur , Monka Julia , Binder Grace , Dayrit Alex , Ayala Raul , O’Brien Neil , De Robertis Edward M.
Published: June 2023

Activation of the Wnt pathway lies at the core of many human cancers. Wnt and macropinocytosis are often active in the same processes, and understanding how Wnt signaling and membrane trafficking cooperate should improve our understanding of embryonic development and cancer. Here we show that a macropinocytosis activator, the tumor promoter Phorbol 12-myristate 13-acetate (PMA), enhances Wnt signaling. Experiments using theXenopusembryo as an in vivo model showed marked cooperation between the PMA phorbol ester and Wnt signaling, which was blocked by inhibitors of macropinocytosis, Rac1 activity, and lysosome acidification. Human colorectal cancer tissue arrays and xenografts in mice showed a correlation of cancer progression with increased macropinocytosis/multivesicular body/lysosome markers and decreased GSK3 levels. The crosstalk between canonical Wnt, focal adhesions, lysosomes, and macropinocytosis suggests possible therapeutic targets for cancer progression in Wnt-driven cancers.
Robust metabolomic age prediction based on a wide selection of metabolites
Authors: Faquih Tariq , van Hylckama Vlieg Astrid , Surendran Praveen , Butterworth Adam S. , Li-Gao Ruifang , de Mutsert Renée , Rosendaal Frits R. , Noordam Raymond , van Heemst Diana , van Dijk Ko Willems , Mook-Kanamori Dennis O.
Published: June 2023

Chronological age is a major risk factor for numerous diseases. However, chronological age does not capture the complex biological aging process. Biological aging can occur at a different pace in individuals of the same chronological age. Therefore, the difference between the chronological age and biologically driven aging could be more informative in reflecting health status. Metabolite levels are thought to reflect the integrated effects of both genetic and environmental factors on the rate of aging, and may thus provide a stronger signature for biological age than those previously developed using methylation and proteomics. Here, we set out to develop a metabolomic age prediction model by applying ridge regression and bootstrapping with 826 metabolites (of which 678 endogenous and 148 xenobiotics) measured by an untargeted high-performance liquid chromatography mass spectrometry platform (Metabolon) in 11,977 individuals (50.2% men) from the INTERVAL study (Cambridge, UK). Participants of the INTERVAL study are relatively healthy blood donors aged 18-75 years. After internal validation using bootstrapping, the models demonstrated high performance with an adjusted R2of 0.82 using the endogenous metabolites only and an adjusted R2of 0.83 when using the full set of 826 metabolites with age as outcome. The latter model performance could be indicative of xenobiotics predicting frailty. In summary, we developed robust models for predicting metabolomic age in a large relatively healthy population with a wide age range.
The genetics of idiopathic intracranial hypertension (IIH): Integration of population studies and clinical data
Authors: Zucker Roei , Kovalerchik Michael , Davidovich Zvika , Banne Ehud , Maharshak Idit , Linial Michal
Published: June 2023

Background

Idiopathic intracranial hypertension (IIH) is a condition characterized by increased intracranial pressure without a known cause. IIH mainly affects overweight and reproductive-age women. Due to elevated intracranial pressure in IIH patients, papilledema (PAP), a disease caused by swelling of the optic disc, often co-occurs. Previous genome-wide association studies (GWAS) of common variants failed to find significant associations.

Methods

We applied genetic association protocols to a cohort of 173 patients diagnosed with IIH or PAP from the UK Biobank (UKB). The results were compared to the FinnGen data. We applied routine and coding GWAS (cGWAS) to a unified cohort of IIH/PAP. We also employed SKAT, which considers all variants within a given segment, and PWAS, which estimates the damage of variants to protein function and models a gene by aggregating its coding variants.

Results

The detection power of standard GWAS methods is restricted by cohort size and false discovery. To overcome these limitations, we considered gene-centric approaches for the unified group of IIH and PAP patients. Notably, the dominant comorbidity of IIH is PAP in the UKB and FinnGen populations. Seeking shared genes by GWAS for IIH and PAP identified VLDLR and SHANK2 genes in the UKB and FinnGen cohorts, respectively. By utilizing complementary gene-centric association protocols (coding GWAS, SKAT, and PWAS) for the unified IIH/PAP group, we identified 16 genes that were recognized by at least two methods, with FOXF1 and RGCC recognized by all three. Employing a functional enrichment scheme emphasized the significance of cilium, microtubule, and cytoskeletal functions. To gain insight into IIH etiology, we focused on the choroid plexus, a brain structure that produces and secretes the cerebrospinal fluid (CSF). Altogether, 7 of the 16 candidate genes are listed among the 281 genes with enhanced expression in the choroid plexus epithelium. Among them, MAPK15, DNAH5, and SLC28A3 are involved in ciliary microtubule dysregulation.

Conclusions

This study highlights the strength of integrative genetic association approaches with functional and clinical knowledge. By identifying potential genetic effects, we propose the biological and cellular relevance of the choroid plexus for IIH etiology and suggest candidate genes for further investigation.
Identification of Novel Syncytiotrophoblast Membrane Extracellular Vesicles Derived Protein Biomarkers in Early-onset Preeclampsia: A Cross-Sectional Study
Authors: Awoyemi Toluwalase , Jiang Shuhan , Bjarkadóttir Bríet , Rahbar Maryam , Logenthiran Prasanna , Collett Gavin , Zhang Wei , Cribbs Adam , Cerdeira Ana Sofia , Vatish Manu
Published: June 2023

Background

Preeclampsia (PE), a multi-systemic hypertensive pregnancy disease that affects 2-8% of pregnancies worldwide, is a leading cause of adverse maternal and fetal outcomes. Current clinical PE tests have a low positive predictive value for PE prediction and diagnosis. The placenta notably releases extracellular vesicles from the syncytiotrophoblast (STB-EV) into the maternal circulation.

Objective

To identify a difference in placenta and STB-EV proteome between PE and normal pregnancy (NP), which could lead to identifying potential biomarkers and mechanistic insights.

Methods

Using ex-vivo dual lobe perfusion, we performed mass spectrometry on placental tissue, medium/large and small STB-EVs isolated from PE (n = 6) and NP (n = 6) placentae. Bioinformatically, mass spectrometry was used to identify differentially carried proteins. Western blot was used to validate the identified biomarkers. We finished our investigation with an in-silico prediction of STB-EV mechanistic pathways.

Results

We identified a difference in the STB-EVs proteome between PE and NP. Filamin B, collagen 17A1, pappalysin-A2, and scavenger Receptor Class B Type 1) were discovered and verified to have different abundances in PE compared to NP. In silico mechanistic prediction revealed novel mechanistic processes (such as abnormal protein metabolism) that may contribute to the clinical and pathological manifestations of PE.

Conclusions

We identified potentially mechanistic pathways and identified differentially carried proteins that may be important in the pathophysiology of PE and are worth investigating because they could be used in future studies of disease mechanisms and as biomarkers.

Funding

This research was funded by the Medical Research Council (MRC Programme Grant (MR/J0033601) and the Medical & Life Sciences translational fund (BRR00142 HE01.01)
Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction
Authors: Franco-Enzástiga Úrzula , Natarajan Keerthana , David Eric T. , Patel Krish J. , Ravirala Abhira , Price Theodore J.
Published: June 2023

Type I interferons (IFNs) increase the excitability of dorsal root ganglion (DRG) neurons via activation of MNK-eIF4E translation signaling to promote pain sensitization in mice. Activation of STING signaling is a key component of type I IFN induction. Manipulation of STING signaling is an active area of investigation in cancer and other therapeutic areas. Vinorelbine is a chemotherapeutic that activates STING and has been shown to cause pain and neuropathy in oncology clinical trials in patients. There are conflicting reports on whether STING signaling promotes or inhibits pain in mice. We hypothesized that vinorelbine would cause a neuropathic pain-like state in mice via STING and signaling pathways in DRG neurons associated with type I IFN induction. Vinorelbine (10 mg/kg, i.v.) induced tactile allodynia and grimacing in WT male and female mice and increased p-IRF3 and type I IFN protein in peripheral nerves. In support of our hypothesis, vinorelbine-mediated pain was absent in male and female StingGt/Gtmice. Vinorelbine also failed to induce IRF3 and type I IFN signaling in these mice. Since type I IFNs engage translational control via MNK1-eIF4E in DRG nociceptors, we assessed vinorelbine-mediated p-eIF4E changes. Vinorelbine increased p-eIF4E in DRG in WT animals but not in StingGt/GtorMknk1-/-(MNK1 KO) mice. Consistent with these biochemical findings, vinorelbine had an attenuated pro-nociceptive effect in male and female MNK1 KO mice. Our findings support the conclusion that activation of STING signaling in the peripheral nervous system causes a neuropathic pain-like state that is mediated by type I IFN signaling to DRG nociceptors.
BILE ACIDS IN LOWER AIRWAYS AS A NOVEL INDICATOR OF AIRWAY MICROBIOTA CHANGES IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Authors: Caparrós-Martín Jose A. , Saladié Montserrat , Agudelo-Romero S. Patricia , Nichol Kristy S. , Reen F. Jerry , Moodley Yuben , Mulrennan Siobhain , Stick Stephen M. , Wark Peter A , O’Gara Fergal
Published: June 2023

Background

Chronic obstructive pulmonary disease (COPD) is a complex disorder with a high degree of interindividual variability. Gastrointestinal dysfunction is common in COPD patients and has been proposed to influence the clinical progression of the disease. Using the presence of bile acid(s) (BA) in bronchoalveolar lavage fluid (BAL) as a marker of gastric aspiration, we evaluated the relationships between BAs, clinical outcomes, and bacterial lung colonisation.

Methods

We used BAL specimens from a cohort of COPD patients and healthy controls. Bile acids were profiled and quantified in BAL supernatants using mass spectrometry. Microbial DNA was extracted from BAL cell pellets and quantified using qPCR. We profiled the BAL microbiota using an amplicon sequencing approach targeting the V3-V4 region of the 16S rRNA gene.

Results

Detection of BAs in BAL was more likely at earliest clinical stages of COPD and was independent of the degree of airway obstruction. BAL specimens with BAs demonstrated higher bacterial biomass and lower diversity. Likewise, the odds of recovering bacterial cultures from BAL were higher if BAs were also detected. Detection of BAs in BAL was not associated with either inflammatory markers or clinical outcomes. We also observed different bacterial community types in BAL, which were associated with different clinical groups, levels of inflammatory markers, and the degree of airway obstruction.

Conclusion

Detection of BAs in BAL was associated with different parameters of airway ecology. Further studies are needed to evaluate whether BAs in BAL can be used to stratify patients and for predicting disease progression trajectories.
Testing the Feasibility, Acceptability and Effectiveness of the Problem Management Plus for Moms: Protocol of a Randomized Control Trial
Authors: Falgas-Bague Irene , Melero-Dominguez Maria , de Vernisy-Romero Daniela , Tembo Thandiwe , Chembe Mpela , Lubozha Theresa , Paul Ravi , Parkerson Doug , Rockers Peter C. , Sikazwe Dorothy , Fink Günther
Published: June 2023

Background

Mental health disorders are one of the most common causes that limit the ability of mothers to care for themselves and their children. Recent data suggest high rates of distress among women in charge of young children in Zambia. Nevertheless, Zambia’s public healthcare offers very limited treatment for common mental health distress. To address this treatment gap, this study aims to test the feasibility, acceptability, and potential efficacy of a context-adapted psychosocial intervention.

Methods

A total of 270 mothers with mental health needs (defined as SRQ-20 scores above 7) will be randomly assigned with equal probability to the intervention or control group. The intervention group will receive a locally adapted version of the Problem-Management Plus and “Thinking positively” interventions developed by the World Health Organization (WHO) combined with specific parts of the Strong Minds-Strong Communities intervention. Trained and closely supervised wellbeing-community health workers will provide the psychosocial intervention. Mental health distress and attendance to the intervention will be assessed at enrollment and 6 months after the intervention. We will estimate the impact of the intervention on mental health distress using an intention-to-treat approach.

Discussion

We previously found that there is a large necessity for interventions that aim to address mother anxiety/depression problems. In this study, we will test the feasibility and efficacy of an innovative intervention, demonstrating that implementing these mental health treatments in low-income settings, such as Zambia, is viable with an adequate support system. If successful, larger studies will be needed to test the effectiveness of the intervention with increased precision.

Trial registration

This study is registered atclinicaltrials.govasNCT05627206.https://www.clinicaltrials.gov/ct2/show/NCT05627206
Association between sleep and seroconversion after vaccination with inactivated SARS-CoV-2 in pregnant women
Authors: Han Xue , Yang Wenhan , Zhang Xi , Chen Baolan , Fu Xi , Huang Jitian , Xu Yingxia , Gong Yajie , Chen Qingsong
Published: June 2023

To assess the association between sleep and seroconversion after receipt of two doses of inactivated severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) vaccines in pregnant women. The serum level of immunoglobulin (Ig)G antibodies against the nucleic acids of SARS-CoV-2 was measured. Logistic regression was used to analyze the association between sleep and seroconversion. After two doses of SARS-CoV-2 vaccine, 41.2% of the study cohort reached seroconversion. Analysis revealed that pregnant women with poor quality of sleep had a lower serum level of IgG antibodies (P= 0.008, 95%CI = 0.285–0.826) and that sleeping late at night (SLaN) may be a risk factor for a low serum level of IgG antibodies (P= 0.025, 95%CI = 0.436–0.946). Besides sleep, age and the time since vaccination were important influences on seroconversion. A stratified analysis revealed that the effects of sleep quality and SLaN on seroconversion occurred mainly in pregnant women aged <35 years. Thus, sleep quality and SLaN can affect the serum level of IgG antibodies in pregnant women after vaccination with inactivated SARS-CoV-2.
An Endpoint Adjudication Committee for the Assessment of Computed Tomography Scans in Fracture Healing
Authors: Elliott Chloe , Patterson Ethan , Mattiello Brenna , Tarcea Adina , Frizzell Bevan , Walker Richard E. , Hildebrand Kevin A. , White Neil J.
Published: June 2023

The use of endpoint adjudication committees (EACs) has the potential to reduce subjectivity and potential bias in clinical research trials and contribute to a higher quality of research. In a recent randomized control trial (RCT), we used serial computed tomography (CT) imaging to visualize fracture healing of the scaphoid as a primary outcome. The scaphoid bone poses a challenge in the diagnosing of fractures and non-unions due to its complicated shape. An EAC was created to increase the quality of the data and the validity of our findings. While an adjudication process has long been proposed and described for X-rays, this study outlines a rational approach to CT scan adjudication for bone fracture healing. A total of 364 scans were acquired in the RCT and of these, 101 were adjudicated for a binary endpoint of union vs. non-union. The application of EACs such as described in this paper is a useful tool in orthopaedic research requiring the adjudication of fracture healing as a study outcome.
The impact of common variants on gene expression in the human brain: from RNA to protein to schizophrenia risk
Authors: Liang Qiuman , Jiang Yi , Shieh Annie W. , Zhou Dan , Chen Rui , Wang Feiran , Xu Meng , Niu Mingming , Wang Xusheng , Pinto Dalila , Wang Yue , Cheng Lijun , Vadukapuram Ramu , Zhang Chunling , Grennan Kay , Giase Gina ,   The PsychENCODE Consortium, White Kevin P , Peng Junmin , Li Bingshan , Liu Chunyu , Chen Chao , Wang Sidney H.
Published: June 2023

Background

The impact of genetic variants on gene expression has been intensely studied at the transcription level, yielding in valuable insights into the association between genes and the risk of complex disorders, such as schizophrenia (SCZ). However, the downstream impact of these variants and the molecular mechanisms connecting transcription variation to disease risk are not well understood.

Results

We quantitated ribosome occupancy in prefrontal cortex samples of the BrainGVEX cohort. Together with transcriptomics and proteomics data from the same cohort, we performed cis-Quantitative Trait Locus (QTL) mapping and identified 3,253 expression QTLs (eQTLs), 1,344 ribosome occupancy QTLs (rQTLs), and 657 protein QTLs (pQTLs) out of 7,458 genes quantitated in all three omics types from 185 samples. Of the eQTLs identified, only 34% have their effects propagated to the protein level. Further analysis on the effect size of prefrontal cortex eQTLs identified from an independent dataset showed clear post-transcriptional attenuation of eQTL effects. To investigate the biological relevance of the attenuated eQTLs, we identified 70 expression-specific QTLs (esQTLs), 51 ribosome-occupancy-specific QTLs (rsQTLs), and 107 protein-specific QTLs (psQTLs). Five of these omics-specific QTLs showed strong colocalization with SCZ GWAS signals, three of them are esQTLs. The limited number of GWAS colocalization discoveries from omics-specific QTLs and the apparent prevalence of eQTL attenuation prompted us to take a complementary approach to investigate the functional relevance of attenuated eQTLs. Using S-PrediXcan we identified 74 SCZ risk genes, 34% of which were novel, and 67% of these risk genes were replicated in a MR-Egger test. Notably, 52 out of 74 risk genes were identified using eQTL data and 70% of these SCZ-risk-gene-driving eQTLs show little to no evidence of driving corresponding variations at the protein level.

Conclusion

The effect of eQTLs on gene expression in the prefrontal cortex is commonly attenuated post-transcriptionally. Many of the attenuated eQTLs still correlate with SCZ GWAS signal. Further investigation is needed to elucidate a mechanistic link between attenuated eQTLs and SCZ disease risk.
Macrophages modulate fibrosis during newt lens regeneration
Authors: Tsissios Georgios , Sallese Anthony , Raul Perez-Estrada J. , Tangeman Jared A. , Chen Weihao , Smucker Byran , Ratvasky Sophia C. , Grajales-Esquivel Erika , Martinez Arielle , Visser Kimberly J. , Araus Alberto Joven , Wang Hui , Simon Andras , Yun Maximina H. , Del Rio-Tsonis Katia
Published: June 2023

Previous studies indicated that macrophages play a role during lens regeneration in newts, but their function has not been tested experimentally. Here we generated a transgenic newt reporter line in which macrophages can be visualizedin vivo. Using this new tool, we analyzed the location of macrophages during lens regeneration. We uncovered early gene expression changes using bulk RNAseq in two newt species,Notophthalmus viridescensandPleurodeles waltl. Next, we used clodronate liposomes to deplete macrophages, which inhibited lens regeneration in both newt species. Macrophage depletion induced the formation of scar-like tissue, an increased and sustained inflammatory response, an early decrease in iris pigment epithelial cell (iPEC) proliferation and a late increase in apoptosis. Some of these phenotypes persisted for at least 100 days and could be rescued by exogenous FGF2. Re-injury alleviated the effects of macrophage depletion and re-started the regeneration process. Together, our findings highlight the importance of macrophages in facilitating a pro-regenerative environment in the newt eye, helping to resolve fibrosis, modulating the overall inflammatory landscape and maintaining the proper balance of early proliferation and late apoptosis.
Mesostriatal dopamine is sensitive to specific cue-reward contingencies
Authors: Garr Eric , Cheng Yifeng , Jeong Huijeong , Brooke Sara , Castell Laia , Bal Aneesh , Magnard Robin , Namboodiri Vijay Mohan K. , Janak Patricia H.
Published: June 2023

Learning causal relationships relies on understanding how often one event precedes another. To gain an understanding of how dopamine neuron activity and neurotransmitter release change when a retrospective relationship is degraded for a specific pair of events, we used outcome-selective Pavlovian contingency degradation in rats. Two cues were paired with distinct food rewards, one of which was also delivered in the absence of either cue. Conditioned approach was attenuated for the cue-reward contingency that was degraded. Dopamine neuron activity in the midbrain and dopamine release in the ventral striatum showed a profile of changes in cue- and reward-evoked responding that was not easily explained by a standard reinforcement learning model. An alternative model based on learning causal relationships was better able to capture evoked dopamine responses during contingency degradation, as well as conditioned behavior following optogenetic manipulations of dopamine during noncontingent rewards. Our results suggest that mesostriatal dopamine encodes the contingencies between meaningful events during learning.
Genetic basis of historical pea mutants that hyper-accumulate iron
Authors: Harrington Sophie A. , Franceschetti Marina , Balk Janneke
Published: June 2023

ThePisum sativum(pea) mutantsdegenerate leaves(dgl) andbronze(brz) accumulate large amounts of iron in leaves. First described several decades ago, the two mutants have provided important insights into iron homeostasis in plants but the underlying mutations have remained unknown. Using exome sequencing we identified an in-frame deletion associated withdglin aBRUTUShomologue. The deletion is absent from wild type and the original parent line. BRUTUS belongs to a small family of E3 ubiquitin ligases acting as negative regulators of iron uptake in plants. Thebrzmutation was previously mapped to chromosome 4, and superimposing this region to the pea genome sequence uncovered a mutation inOPT3, encoding an oligopeptide transporter with a plant-specific role in metal transport. The causal nature of the mutations was confirmed by additional genetic analyses. Identification of the mutated genes rationalises many of the previously described phenotypes and provides new insights into shoot-to-root signalling of iron deficiency. Furthermore, the non-lethal mutations in these essential genes suggest new strategies for biofortification of crops with iron.

Significance statement

Two iron-accumulating pea mutants first described more than 30 years ago have greatly contributed to our understanding of iron homeostasis in plants, but the mutations were never identified. Here we show that the phenotypes are caused by mutations in theBRUTUSandOPT3genes and how this leads to specific defects in iron signalling and leaf development.
Mutatortransposon insertions within maize genes often provide a novel outward reading promoter
Authors: Ellison Erika L. , Zhou Peng , Hermanson Peter , Chu Yi-Hsuan , Read Andrew , Hirsch Candice N. , Grotewold Erich , Springer Nathan M.
Published: June 2023

The highly active family ofMutator(Mu) DNA transposons has been widely used for forward and reverse genetics in maize. There are examples ofMu-suppressible alleles which result in conditional phenotypic effects based on the activity ofMu. Phenotypes from theseMu- suppressible mutations are observed inMu-active genetic backgrounds, but absent whenMuactivity is lost. For someMu-suppressible alleles, phenotypic suppression likely results from an outward-reading promoter withinMuthat is only active when the autonomousMuelement is silenced or lost. We isolated 35Mualleles from the UniformMu population that represent insertions in 24 different genes. Most of these mutant alleles are due to insertions within gene coding sequences, but several 5’ UTR and intron insertions were included. RNA-seq andde novotranscript assembly were utilized to document the transcripts produced from 33 of theseMuinsertion alleles. For 20 of the 33 alleles, there was evidence of transcripts initiating within theMusequence reading through the gene. This outward-reading promoter activity was detected in multiple types ofMuelements and doesn’t depend on the orientation ofMu. Expression analyses ofMu-initiated transcripts revealed theMupromoter often provides gene expression levels and patterns that are similar to the wild-type gene. These results suggest theMupromoter may represent a minimal promoter that can respond to genecis-regulatory elements. Findings from this study have implications for maize researchers using the UniformMu population, and more broadly highlights a strategy for transposons to co-exist with their host.

Article Summary

Mutator(Mu) transposable elements are a widely used tool for insertional mutagenesis in maize and often insert in the 5’ regions of genes. The characterization of transcripts forMuinsertion alleles reveals complex transcripts. These often result in one transcript that covers the first portion of the gene terminating inMuand a second transcript initiating withinMucovering the latter portion of the gene. This may reflect a strategy forMuto minimize the consequences of insertions within genes.
A fresh view on the structure and twinning of owyheeite, a rod-polytype and twofold superstructure
Authors: Stöger Berthold , Göb Christian , Topa Dan
Published: June 2023

Owyheeite [Cu0.09 (1)Ag2.77 (4)Pb10.23 (4)Sb10.89 (5)S28.00 (5)] crystallizes as a twofold superstructure with P21/n symmetry and pseudo-orthorhombic metrics [a = 8.1882 (3) Å, b = 27.2641 (7) Å, c = 22.8679 (7) Å, β = 90.293 (3)°, V = 5105.0 (3) Å3, Z = 4]. Owyheeite is systematically twinned by reflection at (021) or equivalently (021). Twinning is explained by describing a simplified Pmcn archetype structure as polytype built of two kinds of rods, which contact via electron-pair micelles. A procedure of generating hypothetical polytypes by tiling space with partially overlapping equivalent regions is described.
Metal halide coordination compounds with quinazolin-4(3H)-one
Authors: Turgunov Kambarali K. , Englert Ulli
Published: June 2023

Three coordination compounds of quinazolin-4(3H)-one (quinoz; C8H6N2O) with divalent group 12 halides are reported. In all complexes, coordination occurs via the nitrogen atom ortho to the quinazolinone carbonyl group. In the two chain polymers with composition [MX
2(quinoz)], viz. (M = Cd, X = Br), catena-poly[[[quinazolin-4(3H)-one-κN
3]cadmium(II)]-di-μ-bromido], [CdBr2(C8H6N2O)]
n
(I), and M = Hg, X = Cl, catena-poly[[[quinazolin-4(3H)-one-κN
3]mercury(II)]-di-μ-chlorido], [HgCl2(C8H6N2O)]
n
(II), the divalent cations are five-coordinate, with four bridging halide and one terminal quinoz ligand. The CdII atom in (I) has an almost trigonal–bipyramidal coordination environment, whereas the HgII atom in (II) has a more distorted coordination environment. Likewise, the halide bridges in (II) are significantly more asymmetric than in (I). In both (I) and (II), quinoz ligands at adjacent cations along each strand are oriented in opposite directions, and the organic ligands of neighboring strands interdigitate with resulting π–π interactions. In contrast to the halide-bridged chain polymers (I) and (II), the adduct of quinoz with CdI2 is the tetrahedral complex [CdI2(quinoz)2], diiodidobis[quinazolin-4(3H)-one-κN
3]cadmium(II), [CdI2(C16H12N4O2)], (III). The CdII atom in this discrete complex is located on a twofold rotation axis. Disorder in (III) is reflected in an alternative minority orientation of the molecules for which the iodine sites closely match the position of the majority orientation. In view of the low site occupancy of only 0.0318 (8) Å, only the CdII position for this alternative orientation was taken into account during refinement. In all three compounds, classical N—H...O hydrogen bonds with donor–acceptor distances of ca 2.9 Å occur; they link the polymer chains in (I) and (II) into di-periodic networks and connect adjacent discrete complexes in (III) to mono-periodic strands.
Electrochemical impedance characteristics and degradation behaviors of carbon fiber reinforced composite attacked by HF solution
Authors: Xu Huiyi , Gao Zhiming , Yang Yang , Hu Wenbin
Published: June 2023

Purpose

The purpose of this study is to ensure the safe use of carbon fiber composite pressure vessels in the nuclear industry environment.

Design/methodology/approach

This study investigated the degradation behaviors of carbon fiber reinforced composite (CFRP) using the specific corrosive media HF solution, with a focus on the damage to the surface epoxy layer. The degradation behaviors of CFRP in HF solution were examined by electrochemical methods and surface characterization, using HCl, NaCl and NaF solution for comparison.

Findings

The results showed that the specimen in HF solution will have a value of |Z|0.01 Hz one order of magnitude lower, a substantially lower contact angle, more breakage of the surface epoxy and the stronger O─H peak and weaker C─O─C peak in the Fourier transform infrared spectrum, indicating severe hydrolytic damage to the surface epoxy.

Originality/value

The work focuses on the degradation damage to CFRP surface epoxy by specific corrosive media HF.
Corrosion behavior of TiC/amorphous carbon coated stainless steel as bipolar plate for proton exchange membrane fuel cell
Authors: Qin Zhenbo , Li Jiale , Zhang Yiwen , Wu Zhong , Hu Wenbin
Published: June 2023

Purpose

The purpose of this paper is to improve the corrosion resistance of stainless-steel bipolar plate by magnetron sputtering.

Design/methodology/approach

TiC/amorphous carbon composite film was deposited by magnetron sputter at four different temperature of 25°C, 200°C, 300°C and 400°C. The morphology, composition and structure of the film were characterized by scanning electron microscopy, atomic force microscopy and X-ray photoelectron spectroscopy. And its corrosion behavior was analyzed through electrochemical impedance spectroscopy, potentiodynamic and potentiostatic polarization tests.

Findings

A compact TiC/amorphous carbon film was prepared by magnetron sputtering on 316L stainless steel, and the particles of the film were refined with the increase in sputtering temperature. High temperature promoted the formation of TiC and C–C sp2 hybrid carbon, but excessively high temperature caused the oxidation of Ti and a significant decrease in sp2 hybrid carbon. The corrosion resistance of the film increased with the temperature, and the corrosion current density polarization at 0.86 V and 1.8 V for TiC/a–C film prepared at 400 °C is only 1.2% and 43.2% of stainless steel, respectively.

Originality/value

The corrosion resistance of amorphous carbon films was improved by the doping of Ti carbide, and the appropriate sputtering temperature was obtained.