Assessment of Clinician-Reported Outcome Measures for Alopecia Areata: A Systematic Scoping Review.

Clinician-reported outcome measures (ClinROMs) are an important part of disease assessment in daily practice and clinical trials. There is a broad disagreement on the most appropriate ClinROM for a comprehensive assessment of alopecia areata (AA) severity. This paper aims to identify the currently available ClinROMs for AA through a systematic literature search, address their practical strengths and weaknesses, and identify the road ahead for future research. A search was conducted of the published, peer-reviewed literature via PubMed (Medline) and EMBASE (via Ovid) databases. Articles published in English within the last 23 years (post-2000) that objectively measured AA severity were included. We did not select scoring systems that were solely based on patient-reported outcomes (PROs). The literature search identified 1376 articles, of which 27 were chosen for full-text review. Based on our eligibility criteria, fourteen articles were identified, describing sixteen different ClinROMs. Five ClinROMs solely measured scalp hair loss (SALT, SALTⅡ, ALODEX, pSALT, and AA-IGA). Three trichoscopy-based ClinROMs assessed disease activity (AAPI, AAPS, and Coudability hair score). Six ClinROMs exclusively assessed non-scalp areas (BETA, BELA, ALBAS, ClinRO for Eyelash, Eyebrow, and Nail assessment). Two ClinROMs assessed both the scalp and beyond-scalp areas (AASI and AASc). The practical strengths and weaknesses of each assessment tool were described. Various practical limitations associated with established tools have impeded their universal implementation in routine clinical practice. There is a significant need for a holistic clinical severity scoring system to capture all the key severity identifiers beyond the involvement of the scalp.

Synaptic architecture of leg and wing premotor control networks in Drosophila.

Animal movement is controlled by motor neurons (MNs), which project out of the central nervous system to activate muscles1. MN activity is coordinated by complex premotor networks that facilitate the contribution of individual muscles to many different behaviours2-6. Here we use connectomics7 to analyse the wiring logic of premotor circuits controlling the Drosophila leg and wing. We find that both premotor networks cluster into modules that link MNs innervating muscles with related functions. Within most leg motor modules, the synaptic weights of each premotor neuron are proportional to the size of their target MNs, establishing a circuit basis for hierarchical MN recruitment. By contrast, wing premotor networks lack proportional synaptic connectivity, which may enable more flexible recruitment of wing steering muscles. Through comparison of the architecture of distinct motor control systems within the same animal, we identify common principles of premotor network organization and specializations that reflect the unique biomechanical constraints and evolutionary origins of leg and wing motor control.

Connectomic reconstruction of a female Drosophila ventral nerve cord.

A deep understanding of how the brain controls behaviour requires mapping neural circuits down to the muscles that they control. Here, we apply automated tools to segment neurons and identify synapses in an electron microscopy dataset of an adult female Drosophila melanogaster ventral nerve cord (VNC)1, which functions like the vertebrate spinal cord to sense and control the body. We find that the fly VNC contains roughly 45 million synapses and 14,600 neuronal cell bodies. To interpret the output of the connectome, we mapped the muscle targets of leg and wing motor neurons using genetic driver lines2 and X-ray holographic nanotomography3. With this motor neuron atlas, we identified neural circuits that coordinate leg and wing movements during take-off. We provide the reconstruction of VNC circuits, the motor neuron atlas and tools for programmatic and interactive access as resources to support experimental and theoretical studies of how the nervous system controls behaviour.

The Alopecia Areata Severity and Morbidity Index (ASAMI) Study: Results From a Global Expert Consensus Exercise on Determinants of Alopecia Areata Severity.

Importance: Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact. Objective: To explore factors associated with AA severity beyond scalp hair loss, and to support the development of the Alopecia Areata Severity and Morbidity Index (ASAMI). Evidence Review: A total of 74 hair and scalp disorder specialists from multiple continents were invited to participate in an eDelphi project consisting of 3 survey rounds. The first 2 sessions took place via a text-based web application following the Delphi study design. The final round took place virtually among participants via video conferencing software on April 30, 2022. Findings: Of all invited experts, 64 completed the first survey round (global representation: Africa [4.7%], Asia [9.4%], Australia [14.1%], Europe [43.8%], North America [23.4%], and South America [4.7%]; health care setting: public [20.3%], private [28.1%], and both [51.6%]). A total of 58 specialists completed the second round, and 42 participated in the final video conference meeting. Overall, consensus was achieved in 96 of 107 questions. Several factors, independent of the Severity of Alopecia Tool score, were identified as potentially worsening AA severity outcomes. These factors included a disease duration of 12 months or more, 3 or more relapses, inadequate response to topical or systemic treatments, rapid disease progression, difficulty in cosmetically concealing hair loss, facial hair involvement (eyebrows, eyelashes, and/or beard), nail involvement, impaired quality of life, and a history of anxiety, depression, or suicidal ideation due to or exacerbated by AA. Consensus was reached that the Alopecia Areata Investigator Global Assessment scale adequately classified the severity of scalp hair loss. Conclusions and Relevance: This eDelphi survey study, with consensus among global experts, identified various determinants of AA severity, encompassing not only scalp hair loss but also other outcomes. These findings are expected to facilitate the development of a multicomponent severity tool that endeavors to competently measure disease impact. The findings are also anticipated to aid in identifying candidates for current and emerging systemic treatments. Future research must incorporate the perspectives of patients and the public to assign weight to the domains recognized in this project as associated with AA severity.

Synaptic architecture of leg and wing motor control networks in Drosophila.

Animal movement is controlled by motor neurons (MNs), which project out of the central nervous system to activate muscles. Because individual muscles may be used in many different behaviors, MN activity must be flexibly coordinated by dedicated premotor circuitry, the organization of which remains largely unknown. Here, we use comprehensive reconstruction of neuron anatomy and synaptic connectivity from volumetric electron microscopy (i.e., connectomics) to analyze the wiring logic of motor circuits controlling the Drosophila leg and wing. We find that both leg and wing premotor networks are organized into modules that link MNs innervating muscles with related functions. However, the connectivity patterns within leg and wing motor modules are distinct. Leg premotor neurons exhibit proportional gradients of synaptic input onto MNs within each module, revealing a novel circuit basis for hierarchical MN recruitment. In comparison, wing premotor neurons lack proportional synaptic connectivity, which may allow muscles to be recruited in different combinations or with different relative timing. By comparing the architecture of distinct limb motor control systems within the same animal, we identify common principles of premotor network organization and specializations that reflect the unique biomechanical constraints and evolutionary origins of leg and wing motor control.

Australian dermatologists' prescribing behaviours for male androgenetic alopecia.

Androgenetic alopecia (AGA) is highly prevalent among Australian men and can have significant psychological impacts. Despite its prevalence, treatment options have traditionally been limited. In this study, we examined the current prescribing patterns of Australian dermatologists for male AGA.

Cell-type specific transcriptomic signatures of neocortical circuit organization and their relevance to autism.

A prevailing challenge in neuroscience is understanding how diverse neuronal cell types select their synaptic partners to form circuits. In the neocortex, major classes of excitatory projection neurons and inhibitory interneurons are conserved across functionally distinct regions. There is evidence these classes form canonical circuit motifs that depend primarily on their identity; however, regional cues likely also influence their choice of synaptic partners. We mined the Allen Institute's single-cell RNA-sequencing database of mouse cortical neurons to study the expression of genes necessary for synaptic connectivity and physiology in two regions: the anterior lateral motor cortex (ALM) and the primary visual cortex (VISp). We used the Allen's metadata to parse cells by clusters representing major excitatory and inhibitory classes that are common to both ALM and VISp. We then performed two types of pairwise differential gene expression analysis: (1) between different neuronal classes within the same brain region (ALM or VISp), and (2) between the same neuronal class in ALM and VISp. We filtered our results for differentially expressed genes related to circuit connectivity and developed a novel bioinformatic approach to determine the sets uniquely enriched in each neuronal class in ALM, VISp, or both. This analysis provides an organized set of genes that may regulate synaptic connectivity and physiology in a cell-type-specific manner. Furthermore, it identifies candidate mechanisms for circuit organization that are conserved across functionally distinct cortical regions or that are region dependent. Finally, we used the SFARI Human Gene Module to identify genes from this analysis that are related to risk for autism spectrum disorder (ASD). Our analysis provides clear molecular targets for future studies to understand neocortical circuit organization and abnormalities that underlie autistic phenotypes.

Effective treatment of refractory lichen planus pemphigoides with a Janus kinase-1/2 inhibitor.

Lichen planus pemphigoides is a rare autoimmune subepidermal blistering disease clinically and histopathologically characterized by features of lichen planus and bullous pemphigoid. We describe a case of refractory lichen planus pemphigoides successfully treated with the selective and reversible Janus kinase-1/2 inhibitor, baricitinib.