Publications by authors named "Nickels S"

Poor inhibitory control contributes to deficits in emotion regulation, which are often targeted by treatments for major depressive disorder (MDD), including cognitive behavioral therapy (CBT). Brain regions that contribute to inhibitory control and emotion regulation overlap; thus, inhibitory control might relate to response to CBT. In this study, we examined whether baseline inhibitory control and resting state functional connectivity (rsFC) within overlapping emotion regulation-inhibitory control regions predicted treatment response to internet-based CBT (iCBT).

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  • The text discusses the limitations in developing new therapies due to inadequate predictive in vitro models and presents Organ-on-chip (OOC) technologies as a promising solution for improved tissue and disease modeling.
  • It introduces a scalable microfluidic platform called AKITA, designed for high, medium, and low throughput applications compatible with existing laboratory workflows in a standardized format.
  • AKITA is specifically optimized for studying vascularized biological barriers like the blood-brain barrier, using precise flow control and integrated sensors to monitor barrier integrity, ultimately aiding in preclinical drug testing and precision medicine.
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The Patient Health Questionnaire 9 (PHQ-9) is the current standard outpatient screening tool for measuring and tracking the nine symptoms of major depressive disorder (MDD). While the PHQ-9 was originally conceptualized as a unidimensional measure, it has become clear that MDD is not a monolithic construct, as evidenced by high comorbidities with other theoretically distinct diagnoses and common symptom overlap between depression and other diagnoses. Therefore, identifying reliable and temporally stable subfactors of depressive symptoms could allow research and care to be tailored to different depression phenotypes.

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  • The study explores how GBA gene mutations contribute to Parkinson's Disease (PD) by examining patient-derived stem cells and midbrain organoids.
  • Key findings include reduced GCase activity and impaired cell processes like autophagy and mitochondrial function, linked to changes in lipid metabolism.
  • The research highlights a decline in dopaminergic neurons and an increase in neural progenitors showing damage, suggesting that early neurodevelopmental issues may predispose individuals to PD.
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The vast majority of Parkinson's disease cases are idiopathic. Unclear etiology and multifactorial nature complicate the comprehension of disease pathogenesis. Identification of early transcriptomic and metabolic alterations consistent across different idiopathic Parkinson's disease (IPD) patients might reveal the potential basis of increased dopaminergic neuron vulnerability and primary disease mechanisms.

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  • Parkinson's disease (PD) causes problems with movement because certain brain cells that make a chemical called dopamine get damaged over time.
  • Scientists researched using special cells from bone marrow, called mesenchymal stem cells (MSCs), to help treat PD by releasing something called "secretome," which helps protect and heal the brain.
  • They found that using this secretome through multiple smaller shots into the body worked better than just one big shot in the brain, showing promise for helping people with PD in the future.
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  • * This study evaluates the G-RISK regression network using a diverse collection of 149,455 labeled fundus images from multiple reputable sources, confirming its strong performance across challenging data sets.
  • * The G-RISK model achieved high accuracy (AUC values ranging from 0.854 to 0.988) and sensitivity above the recommended threshold, demonstrating good generalizability, although further validation with prospective cohort studies is needed.
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Purpose: Anti-retinal autoantibodies are assumed to be associated with age-related macular degeneration (AMD). To our knowledge, this is the first evaluation of autoantibodies in human sera of participants with different stages of AMD in a large population-based, observational cohort study in Germany.

Methods: The Gutenberg Health Study (GHS) is a population-based, observational cohort study in Germany, including 15,010 participants aged between 35 and 74.

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  • The study investigates the long-term impact of low birth weight (BW) on corneal aberrations in adults, suggesting a potential link to decreased visual function.
  • It analyzed data from over 5,600 participants aged 40-80 and found that lower BW is related to increased spherical aberration and higher root-mean square of higher order aberrations.
  • The findings suggest that low BW might affect corneal shape development, potentially leading to problems with optical image quality and vision.
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The human brain is a complex, three-dimensional structure. To better recapitulate brain complexity, recent efforts have focused on the development of human-specific midbrain organoids. Human iPSC-derived midbrain organoids consist of differentiated and functional neurons, which contain active synapses, as well as astrocytes and oligodendrocytes.

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Errors in performance trigger cognitive and neural changes that are implemented to adaptively adjust to fluctuating demands. Error-related alpha suppression (ERAS)-which refers to decreased power in the alpha frequency band after an incorrect response-is thought to reflect cognitive arousal after errors. Much of this work has been correlational, however, and there are no direct investigations into its pharmacological sensitivity.

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Human brain organoid models that recapitulate the physiology and complexity of the human brain have a great potential for in vitro disease modeling, in particular for neurodegenerative diseases, such as Parkinson disease. In the present study, we compare single-cell RNA-sequencing data of human midbrain organoids to the developing human embryonic midbrain. We demonstrate that the in vitro model is comparable to its in vivo equivalents in terms of developmental path and cellular composition.

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Increasing evidence suggests that neurodevelopmental alterations might contribute to increase the susceptibility to develop neurodegenerative diseases. We investigate the occurrence of developmental abnormalities in dopaminergic neurons in a model of Parkinson's disease (PD). We monitor the differentiation of human patient-specific neuroepithelial stem cells (NESCs) into dopaminergic neurons.

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Purpose: Age-related macular degeneration (AMD) is a major cause of visual impairment and blindness. This study evaluates the incidence and progression of AMD in a large German cohort.

Methods: The Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany that includes 15,010 participants between 35 and 74 years of age.

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Background And Objectives: Pediatric sepsis quality improvement in emergency departments has been well described and associated with improved survival. Acute care (non-ICU inpatient) units differ in important ways, and optimal approaches to improving sepsis processes and outcomes in this setting are not yet known. Our objective was to increase the proportion of acute care sepsis cases in our health system with initial antibiotic order-to-administration time ≤60 minutes by 20% from a baseline of 43% to 52% by December 2020.

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As society has moved past the initial phase of the COVID-19 crisis that relied on broad-spectrum shutdowns as a stopgap method, industries and institutions have faced the daunting question of how to return to a stabilized state of activities and more fully reopen the economy. A core problem is how to return people to their workplaces and educational institutions in a manner that is safe, ethical, grounded in science, and takes into account the unique factors and needs of each organization and community. In this paper, we introduce an epidemiological model (the "Community-Workplace" model) that accounts for SARS-CoV-2 transmission within the workplace, within the surrounding community, and between them.

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Background: Although effective mental health treatments exist, the ability to match individuals to optimal treatments is poor, and timely assessment of response is difficult. One reason for these challenges is the lack of objective measurement of psychiatric symptoms. Sensors and active tasks recorded by smartphones provide a low-burden, low-cost, and scalable way to capture real-world data from patients that could augment clinical decision-making and move the field of mental health closer to measurement-based care.

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Background: Lying on the floor for a long period of time has been described as a critical determinant of prognosis following a fall. In addition to fall-related injuries due to the trauma itself, prolonged immobilization on the floor results in a wide range of comorbidities and may double the risk of death in elderly. Thus, reducing the length of Time On the Ground (TOG) in fallers seems crucial in vulnerable individuals with cognitive disorders who cannot get up independently.

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Glaucoma is a neurodegenerative disease with a structural change of the optic nerve head, leading to visual field defects and ultimately blindness. It has been proposed that glaucoma is associated with increased mortality, but previous studies had methodological limitations (selective study samples, lack of data on potential confounders, self-reported or secondary data on glaucoma diagnoses). We evaluated the association between diagnosed glaucoma and mortality in the population-based National Health and Nutrition Examination Survey (NHANES), a representative health survey in the United States.

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Challenges in therapeutics development for neuropsychiatric disorders can be attributed, in part, to a paucity of translational models capable of capturing relevant phenotypes across clinical populations and laboratory animals. Touch-sensitive procedures are increasingly used to develop innovative animal models that better align with testing conditions used in human participants. In addition, advances in electrophysiological techniques have identified neurophysiological signatures associated with characteristics of neuropsychiatric illness.

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Progress towards understanding neural mechanisms in humans relevant to psychiatric conditions has been hindered by a lack of translationally-relevant cognitive tasks for laboratory animals. Accordingly, there is a critical need to develop parallel neurophysiological assessments of domains of cognition, such as cognitive control, in humans and laboratory animals. To address this, we developed a touchscreen-based cognitive (Eriksen Flanker) task in rats and used its key characteristics to construct a novel human version, with similar testing parameters and endpoints across species.

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Purpose: To investigate the incidence of retinal detachment in the German population and to assess potential risk factors.

Methods: The Gutenberg Health Study is a population-based cohort study in Mainz, Germany, including subjects (n = 15,010) with an age range from 35 to 74 years at baseline examination. Study participants underwent a comprehensive ophthalmological examination including distant-corrected visual acuity, refraction and slit-lamp examination at baseline examination.

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Purpose: This study investigates the relationship between diabetic retinopathy (DR) and birth weight (BW) in diabetic subjects sampled from the general population.

Methods: The Gutenberg Health Study (GHS) is a population-based, observational cohort study in participants aged from 35 to 74 years. Criteria for diabetes diagnosis were HbA1c ≥6.

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