bluuebunny/crossref_metadata_2025_split huggingface dataset:
Christianson Syndrome across the Lifespan: An International Longitudinal Study in Children, Adolescents, and Adults
Authors: Kavanaugh Brian C. , Elacio Jennifer , Best Carrie R. , St. Pierre Danielle G. , Pescosolido Matthew F. , Ouyang Qing , Caruso Paul , Buch Karen , Biedermann John , Bradley Rebecca S. , Liu Judy S. , Jones Richard N. , Morrow Eric M. 
Published: November 2023

ABSTRACTMutations in the X-linked endosomal Na+/H+ Exchanger 6 (NHE6) causes Christianson Syndrome (CS). In the largest study to date, we examine genetic diversity and clinical progression, including cerebellar degeneration, in CS into adulthood. Data were collected as part of the International Christianson Syndrome and NHE6 (SLC9A6) Gene Network Study. Forty-four individuals with 31 unique NHE6 mutations, age 2 to 32 years, were followed prospectively, herein reporting baseline, 1-year follow-up, and retrospective natural history. We present data on the CS phenotype with regard to physical growth, adaptive and motor regression, and across the lifespan, including information on mortality. Longitudinal data on body weight and height were examined using a linear mixed model: the rate of growth across development was slow and resulted in prominently decreased age-normed height and weight by adulthood. Adaptive functioning was longitudinally examined: a majority of adult (18+ years) participants lost gross and fine motor skills over a 1-year follow-up. Previously defined core diagnostic criteria for CS (present in >85%) – namely nonverbal status, intellectual disability, epilepsy, postnatal microcephaly, ataxia, hyperkinesia – were universally present in age 6 to 16; however, an additional core feature of high pain tolerance was added (present in 91%), and furthermore, evolution of symptoms were noted across the lifespan, such that postnatal microcephaly, ataxia and high pain threshold were often not apparent prior to age 6, and hyperkinesis decreased after age 16. While neurologic exams were consistent with cerebellar dysfunction, importantly, a majority of individuals (>50% older than 10) also had corticospinal tract abnormalities. Three participants died during the period of the study. In this large and longitudinal study of CS, we begin to define the trajectory of symptoms and the adult phenotype, thereby identifying critical targets for treatment.
Disentangling heterogeneity in Substance Use Disorders: Insights from Genome-Wide Polygenic Scores
Authors: Vilar-Ribó Laura , Alemany Silvia , Cabana-Domínguez Judit , Llonga Natalia , Arribas Lorena , Grau-López Lara , Daigre Constanza , Cormand Bru , Fernàndez-Castillo Noèlia , Ramos-Quiroga Josep Antoni , Artigas María Soler , Ribasés Marta 
Published: November 2023

AbstractSubstance use disorder (SUD) is a global health problem with significant impact on individuals and society. The presentation of SUD is diverse, involving various substances, ages at onset, comorbid conditions, and disease trajectories. Current treatments for SUD struggle to address this heterogeneity, resulting in high relapse rates. SUD often co-occurs with other psychiatric and mental-health related conditions that contribute to the heterogeneity of the disorder and predispose to adverse disease trajectories. Family and genetic studies highlight the role of genetic and environmental factors in the course of SUD, and point to a shared genetic liability between SUDs and comorbid psychopathology. In this study, we aimed to disentangle SUD heterogeneity using a deeply phenotyped SUD cohort and polygenic scores (PGSs) for psychiatric disorders and related traits. We explored associations between PGSs and various SUD-related phenotypes, as well as PGS-environment interactions using information on lifetime emotional, physical and/or sexual abuse. Our results revealed different patterns of associations between the genetic liability for mental-health related traits and SUD-related phenotypes, which may help explain part of the heterogeneity observed in SUD. In our SUD sample, we found associations linking the genetic liability for ADHD with lower educational attainment, the genetic liability for PTSD with higher rates of unemployment, the genetic liability for educational attainment with lower rates of criminal records and unemployment and the genetic liability for well-being with lower rates of outpatient treatments and fewer problems related to family and social relationships. We also found evidence of PGS-environment interactions showing that genetic liability for suicide attempt worsened the psychiatric status in SUD individuals with a history of emotional physical and/or sexual abuse. Collectively, these data contribute to a better understanding of the role of the genetic liability for mental health-related conditions and adverse life experiences in SUD heterogeneity.
Urine proteomic analysis of patients with schizophrenia
Authors: Zhao Chenyang , Dong Fang , Zhou Fuchun , Huan Yuhang , Yang Jian , Gao Youhe 
Published: November 2023

AbstractWe tried to explore the difference of urinary proteome between unmedicated schizophrenia patients and normal people through a small number of cases. The results showed that a total of 35 differential proteins were screened in the schizophrenia group compared with the healthy control group. Through random grouping evaluation, it has 91.4 % credibility. Fifteen of the differentially expressed proteins were reported to be related to schizophrenia mechanism, drug target or nervous system regulation. Among them, the aromatic amino acid decarboxylase related to the pathogenesis of schizophrenia can distinguish all 10 patients and 9 normal people with 100 % accuracy in this study, and the AUC value of 17 proteins is greater than or equal to 0.9. The biological pathways enriched by differentially expressed proteins include ephrin receptor signaling pathway, positive regulation of long-term potentiation (LTP), etc. This study shows that urine proteomics can reflect the difference between schizophrenia and healthy controls, and has the potential as a diagnostic marker.
Prosthetic Visual Acuity with the PRIMA System in Patients with Atrophic Age-related Macular Degeneration at 4 years follow-up
Authors: Muqit MMK. , Le Mer Y. , Olmos de Koo L , Holz FG , Sahel JA , Palanker D. 
Published: November 2023

AbstractObjectiveTo assess the efficacy and safety of the PRIMA subretinal neurostimulation system 48-months post-implantation for improving visual acuity (VA) in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD) at 48-months post-implantation.DesignFirst-in-human clinical trial of the PRIMA subretinal prosthesis in patients with atrophic AMD, measuring best-corrected ETDRS VA (Clinicaltrials.govNCT03333954).SubjectsFive patients with GA, no foveal light perception and VA of logMAR 1.3 to 1.7 in their worse-seeing “study” eye.MethodsIn patients implanted with a subretinal photovoltaic neurostimulation array containing 378 pixels of 100 μm in size, the VA was measured with and without the PRIMA system using ETDRS charts at 1 meter. The system’s external components: augmented reality glasses and pocket computer, provide image processing capabilities, including zoom.Main Outcome MeasuresVA using ETDRS charts with and without the system. Light sensitivity in the central visual field, as measured by Octopus perimetry. Anatomical outcomes demonstrated by fundus photography and optical coherence tomography up to 48-months post- implantation.ResultsAll five subjects met the primary endpoint of light perception elicited by the implant in the scotoma area. In one patient the implant was incorrectly inserted into the choroid. One subject died 18-months post-implantation due to study-unrelated reason. ETDRS VA results for the remaining three subjects are reported herein. Without zoom, VA closely matched the pixel size of the implant: 1.17 ± 0.13 pixels, corresponding to mean logMAR 1.39, or Snellen 20/500, ranging from 20/438 to 20/565. Using zoom at 48 months, subjects improved their VA by 32 ETDRS letters versus baseline (SE 5.1) 95% CI[13.4,49.9], p<0.0001. Natural peripheral visual function in the treated eye did not decline after surgery compared to the fellow eye (p=0.08) during the 48 months follow-up period.ConclusionsSubretinal implantation of PRIMA in subjects with GA suffering from profound vision loss due to AMD is feasible and well tolerated, with no reduction of natural peripheral vision up to 48-months. Using prosthetic central vision through photovoltaic neurostimulation, patients reliably recognized letters and sequences of letters,and with zoom it provided a clinically meaningful improvement in VA of up to eight ETDRS lines.
Development of supramolecular anticoagulants with on-demand reversibility
Authors: Dockerill Millicent , Ford Daniel J. , Angerani Simona , Alwis Imala , Ripoll-Rozada Jorge , Smythe Rhyll E. , Liu Joanna S.T. , Barbosa Pereira Pedro José , Jackson Shaun P. , Payne Richard J. , Winssinger Nicolas 
Published: November 2023

AbstractDrugs are administered at a dosing schedule set by their therapeutic index and termination of action is achieved by clearance and metabolism of the drug (hours to days for small molecules, weeks to months for biologics). In some cases, it is important to achieve a fast reversal of the drug’s action to overcome dangerous side effects or in response to unforeseen events. A case in point is for anticoagulant drugs. Here we report a general strategy to achieve on-demand reversibility by leveraging supramolecular assembly of drug fragments and showcase the approach with thrombin-inhibiting anticoagulants. In our supramolecular drug design, the action of the drug is reinforced by a dynamic hybridisation of peptide nucleic acids (PNAs) between drug fragments. We show that this design enables the generation of very potent bivalent direct thrombin inhibitors (Ki74 pM) and this inhibition can be reversed through the use of a PNA antidote. We demonstrate that these supramolecular inhibitors exhibit potent anticoagulant activityin vitroandin vivoand that this activity can also be reversed on demand.
How copper based grape pest management has impacted wine aroma
Authors: De Guidi Irene , Galeote Virginie , Blondin Bruno , Legras Jean-Luc 
Published: November 2023

ABSTRACTDespite the high energetic cost of the reduction of sulfate to H2S, required for the synthesis of sulfur-containing amino acids, some wineSaccharomyces cerevisiaestrains have been reported to produce excessive amounts of H2S during alcoholic fermentation, which is detrimental to wine quality. Surprisingly, in the presence of sulfite, used as a preservative, wine strains produce more H2S than wild (oak) or wine velum (flor) isolates during fermentation. Since copper resistance caused by the amplification of the sulfur rich protein Cup1p is a specific adaptation trait of wine strains, we analyzed the link between copper resistance mechanism and H2S production. We show that a higher content of copper in the must increases the production of H2S. Using a set of 51 strains we observed a positive and then negative relation between the number of copies ofCUP1and H2S production during fermentation. This complex pattern could be mimicked using a multicopy plasmid carryingCUP1, confirming the relation between copper resistance and H2S production. The massive use of copper for vine sanitary management has led to the selection of resistant strains at the cost of a metabolic tradeoff: the overproduction of H2S, resulting in a decrease in wine quality.
Impact of non-invasive ventilation on exacerbation frequency in COPD patients
Authors: Zimmermann Maximilian , Margalitadze Georgi , Kroppen Doreen , Windisch Wolfram , Majorski Daniel S , Berger Melanie , Stanzel Sarah B , Wollsching-Strobel Maximilian 
Published: November 2023

AbstractBACKGROUNDAcute exacerbations of COPD are key events in the natural course of the patients illness, as they significantly impair the health condition, accelerate the deterioration of lung function, worsen the prognosis for the patient and account for the majority of the COPD-related healthcare costs. Particularly in patients with a pre-existing non-invasive ventilation (NIV) therapy, a reduction of exacerbation frequency is crucial, as they are at high risk for a lasting morbidity and increased mortality.METHODOLOGYA prospective cohort study was conducted. Data from adult patients with the diagnosis COPD and existing High-Intensity NIV (HINIV) therapy from August 2021 to September 2023 was analyzed. Exacerbation history of moderate and severe exacerbations of the past 12 months and blood gases at initiation and during HINIV therapy were analyzed.RESULTS20 patients were included (mean age 69.2±9 years; 70% female). After initiation of HINIV therapy the frequency of exacerbation displayed a significant reduction from 1.5±0.9 to 0.5±0.5 per year (p<0.001). In addition, improvements in pCO2(73.0±22.0 mmHg vs. 44.0±4.8 mmHg; p<0.001), the pH (7.33±0.1 vs. 7.42±0.0; p<0.001) and HCO3-(33.0±4.9 mmol/l vs. 27.9±3.2 mmol/l; p<0.001) were successfully demonstrated.DISCUSSIONThe present study demonstrates the positive effects of high-intensity NIV on exacerbation rate, measured by the number of moderate and severe exacerbations in one year. Most significant effects were observed when patients had a high number of exacerbations before the initiation of NIV therapy.What are the main findings?A significant reduction in the number of exacerbations was demonstrated with HINIV.There was a strong reduction in the frequency of exacerbations, especially in patients with a high frequency of exacerbations before the HINIV therapy was initiated.What are the implications of the main findings?The exacerbation history should be a more important factor in determining the indication for NIV therapy.Further studies on the pathophysiological causes must follow in order to comprehensively assess the therapeutic effects of NIV.
Psychometric properties of the Dutch London Measure of Unplanned Pregnancy for pregnant people and their partners
Authors: Sprenger Merel , Beumer Wieke Y. , van Ditzhuijzen Jenneke , Kiefte-de Jong Jessica C. 
Published: November 2023

AbstractContextIt is often unclear what constitutes an unplanned or unintended pregnancy, and pregnancy intentions may be multidimensional dynamic. The London Measure of Unplanned Pregnancy (LMUP) measures pregnancy intentions in a manner close to the actual experience. The aim of this study is to establish a Dutch version of the LMUP (LMUP-NL) and to evaluate the reliability and validity of this version for both people who were pregnant and their partners, whatever the pregnancy outcome.MethodsA psychometric evaluation of the LMUP using observational data from the BluePrInt study and the RISE UP study was conducted with 1201 people (839 people who were pregnant and 362 partners), aged between 16-55 years. The LMUP-NL was translated based using the Flemish LMUP and the UK 2020 update, resulting in a version for people who were pregnant and one for partners. Next, the acceptability, readability, reliability, construct and convergent validity were analyzed, combining Principal Component analysis, Confirmatory Factor analysis and Mokken scale analyses.ResultsThe LMUP-NL demonstrated to be readable and reliable (Cronbach’s alpha >0.80 for both versions). Construct validity of both versions was acceptable (CFI>0.93) and Mokken scale analyses indicated a strong scale (H-coefficient:0.68).ConclusionsThe LMUP-NL is reliable and valid for people who were pregnant and their partners, regardless of the pregnancy outcome. It offers researchers and policy makers an instrument suitable to measure pregnancy intention in a multidimensional manner, constituting a closer reflection of the actual experience of pregnancy intentions.
Thermodynamically-consistent, reduced models of gene regulatory networks
Authors: Pan Michael , Gawthrop Peter J. , Faria Matthew , Johnston Stuart T. 
Published: November 2023

AbstractSynthetic biology aims to engineer novel functionalities into biological systems. While the approach has to date been predominantly applied to single cells, a richer set of biological phenomena can be engineered by applying synthetic biology to cell populations. To rationally design cell populations, we require mathematical models that link between intracellular biochemistry and intercellular interactions. In this study, we develop a kinetic model of gene expression that is suitable for incorporation into agent-based models of cell populations. To be scalable to large cell populations, models of gene expression should be both computationally efficient and compliant with the laws of physics. We satisfy the first requirement by applying a model reduction scheme to translation, and the second requirement by formulating models using bond graphs. Our reduced model is significantly faster to simulate than the full model, and faithfully reproduces important behaviours of the full model. We couple separate models of gene expression to build models of the toggle switch and repressilator. With these models, we explore the effects of resource availability and cell-to-cell heterogeneity on circuit behaviour. The modelling approaches developed in this study are a bridge towards engineering collective cell behaviours such as synchronisation and division of labour.
In-vivodistributed multicellular control of gene expression in microbial consortia
Authors: Salzano Davide , Shannon Barbara , Grierson Claire , Marucci Lucia , Savery Nigel J , di Bernardo Mario 
Published: November 2023

AbstractThis paper presents an innovative approach in synthetic biology, focusing on the engineering of biomolecular feedback control systems within microbial consortia to achieve robust and precise regulation of desired phenotypes. Traditional biomolecular control strategies, while effective, are predominantly confined to single-cell applications, limiting their complexity and adaptability due to metabolic constraints. We propose a novel methodology that distributes control functionalities across different cell populations within a microbial consortium. This approach leverages the division of labor and cooperative interactions among microbial populations, significantly enhancing flexibility and robustness. We build on the foundation of synthetically engineered microbial consortia, known for their applications in complex compound production and advanced computational processes. However, the challenge of implementing a distributed feedback control loop for precise phenotype regulation in synthetic communities has remained unaddressed. Our work closes this gap by developing and validating an in-vivo feedback control loop distributed across a bacterial consortium, specifically designed using two Escherichia coli strains. These strains are engineered to perform the three essential control functions: computation, sensing, and actuation. We employ orthogonal quorum sensing signaling molecules for communication between the controller and target cell populations. Through in-vivo experiments, we compare closed-loop and open-loop configurations to demonstrate the effectiveness of our approach. The results show that our distributed control system can regulate gene expression levels in target populations with high precision and robustness, even in the presence of consortium composition variations. This feature is particularly vital for practical applications in synthetic biology where stability and adaptability are crucial. Our study not only addresses a significant gap in synthetic biology literature but also opens avenues for more complex and reliable synthetic biology applications.
Reporting controversial issues in controversial industries
Authors: Marshall Donna , Rehme Jakob , O'Dochartaigh Aideen , Kelly Stephen , Boojihawon Roshan , Chicksand Daniel 
Published: November 2023

PurposeThis article explores how companies in multiple controversial industries report their controversial issues. For the first time, the authors use a new conceptualization of controversial industries, focused on harm and solutions, to investigate the reports of 28 companies in seven controversial industries: Agricultural Chemicals, Alcohol, Armaments, Coal, Gambling, Oil and Tobacco.Design/methodology/approachThe authors thematically analyzed company reports to determine if companies in controversial industries discuss their controversial issues in their reporting, if and how they communicate the harm caused by their products or services, and what solutions they provide.FindingsFrom this study data the authors introduce a new legitimacy reporting method in the controversial industries literature: the solutions companies offer for the harm caused by their products and services. The authors find three solution reporting methods: no solution, misleading solution and less-harmful solution. The authors also develop a new typology of reporting strategies used by companies in controversial industries based on how they report their key controversial issue and the harm caused by their products or services, and the solutions they offer. The authors identify seven reporting strategies: Ignore, Deny, Decoy, Dazzle, Distort, Deflect and Adapt.Research limitations/implicationsFurther research can test the typology and identify strategies used by companies in different institutional or regulatory settings, across different controversial industries or in larger populations.Practical implicationsInvestors, consumers, managers, activists and other stakeholders of controversial companies can use this typology to identify the strategies that companies use to report controversial issues. They can assess if reports admit to the controversial issue and the harm caused by a company's products and services and if they provide solutions to that harm.Originality/valueThis paper develops a new typology of reporting strategies by companies in controversial industries and adds to the theory and discourse on social and environmental reporting (SER) as well as the literature on controversial industries.
Remittances and agricultural productivity: the effect of heterogeneity in economic activity of farming households in Ghana
Authors: Eghan Mark , Adjasi Charles 
Published: November 2023

PurposeThis paper aims to test the impact of remittances receipt on agricultural productivity. The paper empirically assesses whether heterogeneity in economic activity of farming households affects the effects of remittances on productivity of tradable and nontradable crop farming households in Ghana.Design/methodology/approachThe authors employ propensity score matching (PSM) methods to address potential endogeneity issues that could arise from the estimation due to selection bias. This paper uses the seventh round of Ghana living standard survey dataset for Ghana.FindingsThe authors find that, the involvement of farming households in other economic activities alters the impact of remittances on crop yield. This differential impact also varies according whether the crop is tradeable or not.Practical implicationsPolicy can reduce the cost of sending remittances and include financial literacy modules in the farmer training modules to increase farmers' knowledge on investment of remittance in agricultural production.Originality/valueThe authors distinguish the paper from others by controlling for crop types (particularly tradeable or otherwise and gestation period), farming of a second or more crops and engagement of smallholder farmers in nonfarm economic activities.