Virtual Orientation Tools (VOTj): Fiji plugins for object centering and alignment.

Standardizing image datasets is essential for facilitating overall visual comparisons and enhancing compatibility with image-processing workflows. One way to achieve homogeneity for images containing a single object is to align the object to a common orientation. Here, we propose the Virtual Orientation Tools (VOTj): a set of Fiji plugins to center and align an object of interest in images to a vertical or horizontal orientation.

A Novel Ergonomic Curette Design Reduces Dental Prophylaxis-Induced Muscle Work and Fatigue.

Background: To compare fatigue, comfort, and muscle work associated with the use of two periodontal curettes during scaling: one with a novel adaptive design, the other with a conventional non-adaptive design.

Methods: Twelve hygienists scaled a typodont using two Universal Barnhart 5/6 curettes: (1) a prototype featuring an adaptive silicone-covered handle (Curette A), and (2) a stainless-steel curette (Curette B). Surface Electromyography (sEMG) traced muscle work.

A Novel High-Content Screening Assay Identified Belinostat as Protective in a FSGS-Like Zebrafish Model.

Background: FSGS affects the complex three-dimensional morphology of podocytes, resulting in loss of filtration barrier function and the development of sclerotic lesions. Therapies to treat FSGS are limited, and podocyte-specific drugs are unavailable. To address the need for treatments to delay or stop FSGS progression, researchers are exploring the repurposing of drugs that have been approved by the US Food and Drug Administration (FDA) for other purposes.

The ShGlom Combines High-Throughput Drug Screening With Downstream Analyses and Reveals the Protective Role of Vitamin D3 and Calcipotriol on Podocytes.

Chronic kidney disease (CKD) is a major public health burden affecting more than 500 million people worldwide. Podocytopathies are the main cause for the majority of CKD cases due to pathogenic morphological as well as molecular biological alterations of postmitotic podocytes. Podocyte de-differentiation is associated with foot process effacement subsequently leading to proteinuria.

Finding the right fit: evaluation of short-read and long-read sequencing approaches to maximize the utility of clinical microbiome data.

A long-standing challenge in human microbiome research is achieving the taxonomic and functional resolution needed to generate testable hypotheses about the gut microbiota's impact on health and disease. With a growing number of live microbial interventions in clinical development, this challenge is renewed by a need to understand the pharmacokinetics and pharmacodynamics of therapeutic candidates. While short-read sequencing of the bacterial 16S rRNA gene has been the standard for microbiota profiling, recent improvements in the fidelity of long-read sequencing underscores the need for a re-evaluation of the value of distinct microbiome-sequencing approaches.

Visual Search in Naturalistic Scenes Reveals Impaired Cognitive Processing Speed in Multiple Sclerosis.

Background: Standardized neuropsychological testing serves to quantify cognitive impairment in multiple sclerosis (MS) patients. However, the exact mechanism underlying the translation of cognitive dysfunction into difficulties in everyday tasks has remained unclear. To answer this question, we tested if MS patients with intact vs.

Early-onset, fatal interstitial lung disease in STAT3 gain-of-function patients.

Gain-of-function variants in STAT3 are known to cause severe, multifaceted autoimmunity. Here we report three individuals with de-novo STAT3 GOF alleles and early-onset, severe interstitial lung disease manifesting during the first 3 years of life. Imaging and histology revealed different forms of interstitial pneumonia alongside fibrotic and cystic tissue destruction.

Fiji plugins for qualitative image annotations: routine analysis and application to image classification.

Quantitative measurements and qualitative description of scientific images are both important to describe the complexity of digital image data. While various software solutions for quantitative measurements in images exist, there is a lack of simple tools for the qualitative description of images in common user-oriented image analysis software. To address this issue, we developed a set of Fiji plugins that facilitate the systematic manual annotation of images or image-regions.

Impact of psychiatric distress and physical disability on quality of life in neuromyelitis optica spectrum disorder and chronic autoimmune demyelinating polyneuropathies.

Background: Determinants of quality of life (QoL) in demyelinating disorders have been investigated predominantly for multiple sclerosis, especially with regard to "soft clinical signs" such as psychiatric distress. In this exploratory study, we aimed to identify common determinants of QoL for both central and peripheral demyelination in the understudied disease entities of neuromyelitis optica spectrum disorder (NMOSD) and chronic autoimmune demyelinating polyneuropathy (CADP).

Methods: 20 NMOSD and 16 CADP patients were evaluated for physical disability (EDSS and INCAT ODSS), cognitive dysfunction (neuropsychological test battery), psychiatric distress (SCL-90-R), depression (BDI), fatigue (FSMC) and quality of life (EQ-5D-3 L).

Observation and assessment of acoustic contamination of electrophysiological brain signals during speech production and sound perception.

Objective: A current challenge of neurotechnologies is to develop speech brain-computer interfaces aiming at restoring communication in people unable to speak. To achieve a proof of concept of such system, neural activity of patients implanted for clinical reasons can be recorded while they speak. Using such simultaneously recorded audio and neural data, decoders can be built to predict speech features using features extracted from brain signals.

High-Content Screening in Zebrafish for Developmental Nephrotoxicity of Approved Drugs.

Despite widespread drug exposure, for example during gestation or in prematurely born children, organ-specific developmental toxicity of most drugs is poorly understood. Developmental and functional abnormalities are a major cause of kidney diseases during childhood; however, the potential causal relationship to exposure with nephrotoxic drugs during nephrogenesis is widely unknown. To identify developmental nephrotoxic drugs in a large scale, we established and performed an automated high-content screen to score for phenotypic renal alterations in the zebrafish line.

A Multiparametric Assay Platform for Simultaneous In Vivo Assessment of Pronephric Morphology, Renal Function and Heart Rate in Larval Zebrafish.

Automated high-throughput workflows allow for chemical toxicity testing and drug discovery in zebrafish disease models. Due to its conserved structural and functional properties, the zebrafish pronephros offers a unique model to study renal development and disease at larger scale. Ideally, scoring of pronephric phenotypes includes morphological and functional assessments within the same larva.

Automated high-throughput heartbeat quantification in medaka and zebrafish embryos under physiological conditions.

Accurate quantification of heartbeats in fish models is an important readout to study cardiovascular biology, disease states and pharmacology. However, dependence on anaesthesia, laborious sample orientation or requirement for fluorescent reporters have hampered the use of high-throughput heartbeat analysis. To overcome these limitations, we established an efficient screening assay employing automated label-free heart rate determination of randomly oriented, non-anesthetized medaka (Oryzias latipes) and zebrafish (Danio rerio) embryos in microtiter plates.

Multi-template matching: a versatile tool for object-localization in microscopy images.

Background: The localization of objects of interest is a key initial step in most image analysis workflows. For biomedical image data, classical image-segmentation methods like thresholding or edge detection are typically used. While those methods perform well for labelled objects, they are reaching a limit when samples are poorly contrasted with the background, or when only parts of larger structures should be detected.

Patients with chronic autoimmune demyelinating polyneuropathies exhibit cognitive deficits which might be associated with CSF evidence of blood-brain barrier disturbance.

Background: Chronic autoimmune demyelinating polyneuropathies (CADP) result in impaired sensorimotor function. However, anecdotal clinical observations suggest the development of cognitive deficits during the course of disease.

Methods: We tested 16 patients with CADP (11 patients with chronic inflammatory demyelinating polyneuropathy, 4 patients with multifocal motor neuropathy and 1 patient with multifocal acquired demyelinating sensory and motor neuropathy) and 40 healthy controls (HC) with a neuropsychological test battery.

Diarrhea as a Potential Cause and Consequence of Reduced Gut Microbial Diversity Among Undernourished Children in Peru.

Background: Detrimental effects of diarrhea on child growth and survival are well documented, but details of the underlying mechanisms remain poorly understood. Recent evidence demonstrates that perturbations to normal development of the gut microbiota in early life may contribute to growth faltering and susceptibility to related childhood diseases. We assessed associations between diarrhea, gut microbiota configuration, and childhood growth in the Peruvian Amazon.

A sparse covarying unit that describes healthy and impaired human gut microbiota development.

Characterizing the organization of the human gut microbiota is a formidable challenge given the number of possible interactions between its components. Using a statistical approach initially applied to financial markets, we measured temporally conserved covariance among bacterial taxa in the microbiota of healthy members of a Bangladeshi birth cohort sampled from 1 to 60 months of age. The results revealed an "ecogroup" of 15 covarying bacterial taxa that provide a concise description of microbiota development in healthy children from this and other low-income countries, and a means for monitoring community repair in undernourished children treated with therapeutic foods.

Low-Frequency Oscillations Code Speech during Verbal Working Memory.

The way the human brain represents speech in memory is still unknown. An obvious characteristic of speech is its evolvement over time. During speech processing, neural oscillations are modulated by the temporal properties of the acoustic speech signal, but also acquired knowledge on the temporal structure of language influences speech perception-related brain activity.

Cognitive Impairment in Multiple Sclerosis Is Reflected by Increased Susceptibility to the Sound-Induced Flash Illusion.

To determine whether the performance of multiple sclerosis (MS) patients in the sound-induced flash illusion (SiFi), a multisensory perceptual illusion, would reflect their cognitive impairment. We performed the SiFi task as well as an extensive neuropsychological testing in 95 subjects [39 patients with relapse-remitting MS (RRMS), 16 subjects with progressive multiple sclerosis (PMS) and 40 healthy control subjects (HC)]. MS patients reported more frequently the multisensory SiFi than HC.

A Smart Imaging Workflow for Organ-Specific Screening in a Cystic Kidney Zebrafish Disease Model.

The zebrafish is being increasingly used in biomedical research and drug discovery to conduct large-scale compound screening. However, there is a lack of accessible methodologies to enable automated imaging and scoring of tissue-specific phenotypes at enhanced resolution. Here, we present the development of an automated imaging pipeline to identify chemical modifiers of glomerular cyst formation in a zebrafish model for human cystic kidney disease.

Determinants of quality of life in relapsing-remitting and progressive multiple sclerosis.

Background: Numerous factors can affect multiple sclerosis (MS) patients' quality of life (QoL). We investigated how physical impairment, upper extremity function, cognitive impairment, cognitive reserve, symptoms of psychological distress, depression, fatigue as well as age and disease duration contribute to patient-reported measures of QoL in relapse-remitting MS (RRMS) and progressive MS (PMS).

Methods: 39 patients with RRMS and 16 patients with PMS were evaluated for physical impairment (EDSS assessed by a neurologist), upper extremity function (9-hole peg test), cognitive deficits (broad neuropsychological test battery), cognitive reserves (highest obtained degree of education and vocabulary), symptoms of psychological distress (Symptom Checklist-90-R), depression (Beck Depression Inventory) and fatigue (Fatigue Scale for Motor and Cognitive Functions).