Baricitinib Withdrawal and Retreatment in Patients With Severe Alopecia Areata: The BRAVE-AA1 Randomized Clinical Trial.

Importance: Baricitinib has demonstrated efficacy for treating severe alopecia areata in adults. There is currently limited information about the need for continuous therapy after achieving scalp hair regrowth. Objective: To report results from the randomized withdrawal period of the BRAVE-AA1 trial. Design, Setting, and Participants: BRAVE-AA1 was a randomized, placebo-controlled, phase 3 randomized clinical trial with a treatment withdrawal substudy that was conducted at 70 centers in 3 countries beginning in March 2019. It included 654 adults with severe alopecia areata (AA) (Severity of Alopecia Tool [SALT] score ≥50) who were randomized 3:2:2 to receive treatment with baricitinib, 4 mg; baricitinib, 2 mg; or placebo. Data were analyzed in August 2023. Intervention: At week 52, 154 patients who were responders (SALT score ≤20) were rerandomized 3:1 to continue to take their current dose of baricitinib or transition to placebo (randomized withdrawal). Responders randomized to placebo who experienced a loss of treatment benefit (>20-point worsening in SALT score) at any time after week 52 were retreated with their original baricitinib dose. Main Outcome and Measures: The proportion of patients who lost treatment benefit through week 152 and the proportion of patients who recaptured response after retreatment. The last observation carried forward was used to impute missing or censored data. Results: Of 654 patients who received treatment, the mean (SD) age was 37.1 (13.0) years, and there were 383 women (58.6%). At week 52, 10 of 39 responders taking baricitinib, 2 mg, and 30 of 115 responders taking baricitinib, 4 mg, were rerandomized to placebo. At 4 and 8 weeks of treatment withdrawal, 0% and 10% to 11% of patients, respectively, lost treatment benefit regardless of dose. At week 152, 80% of patients had lost benefit compared with 7% for those who continued baricitinib therapy for both dose groups. Within the follow-up observation periods, 5 of 8 patients taking 2 mg (63%) and 21 of 24 patients taking 4 mg (87.5%) recaptured a SALT score of 20 or less response after retreatment. Conclusions and Relevance: Severe AA is a chronic, relapsing condition, and this randomized clinical trial found that withdrawal of therapy for a patient population with severe AA who had achieved meaningful hair regrowth after 1 year of treatment with baricitinib resulted in loss of benefit for almost all patients, indicating that continued therapy is required to maintain hair regrowth. Trial Registration: ClinicalTrials.gov Identifier: NCT03570749.

Treatment patterns and healthcare resource utilization among patients with alopecia areata: A real-world chart review in South Korea.

Alopecia areata (AA) is a clinically heterogeneous, immune-mediated, non-scarring hair loss disorder. This real-world chart review sought to characterize treatment patterns and healthcare resource use among patients with severe AA in South Korea. A web-based chart review of 40 dermatologists was conducted in which the medical charts of 151 adult patients diagnosed with severe AA between May 2019 and April 2021 were reviewed. Anonymized data on patient characteristics, treatment patterns, healthcare resource use, and clinical outcomes were extracted from the date of severe disease diagnosis until the date of data collection (September-November 2022). Sixty-six percent of patients were diagnosed with severe disease at initial presentation, while 34% were re-classed to severe during the disease course. Mean estimated patient age at the time of diagnosis of severe AA was 37.1 (range 22-68) years. Fifty-three percent of patients were male. Most patients (93.4%) received pharmacological treatment for their condition; 45.5% received ≥2 lines of treatment with a mean duration of 24 months. First-line treatment discontinuation due to lack of efficacy occurred in 46.0% of cases. Hair regrowth occurred in 71.0% of patients, 59.2% of whom experienced major regrowth (≥60%) during the follow-up period. Median (95% confidence interval) time to regrowth was 13.7 (11.0-20.6) months. Treatment visit rates per person-year ranged from two (phototherapy) to 10 (topical treatment), dermatologist visits occurred at a rate of 12.9 per person-year and 6.0% of patients were hospitalized due to alopecia areata. The majority of hospitalizations were related to treatment and occurred in patients who received pulse systemic corticosteroid therapy. The patient and economic burden of AA in South Korea is high and there remains a critical unmet need among patients with severe AA with respect to the effectiveness of commonly used treatment strategies.

Korean Consensus Criteria for the Severity Classification of Alopecia Areata.

BACKGROUND: A set of criteria for severity classification is essential in alopecia areata (AA). Currently, no guidelines are universally accepted for defining AA severity. OBJECTIVE: This study aimed to establish a set of consensus criteria for classifying the severity of and identifying treatment refractoriness in AA. METHODS: A preliminary draft of the definition for moderate-to-severe AA was crafted based on available evidence, and members of the Korean Hair Research Society (KHRS) subsequently endorsed the recommendation through an online survey. RESULTS: In the first Delphi round, consensus was attained on 15 questions. After refining certain items in the second round, consensus was achieved on 23 out of 26 questions. The KHRS first defined AA severity using the severity of alopecia tool (SALT). SALT ≥50 was defined as severe, 20≤ SALT <50 as moderate, and SALT <20 as mild. Moderate AA was considered severe if it meets one or more of the following criteria: dermatology life quality index >10, presence of accompanying eyebrow or eyelash loss, positive hair loss activity, or treatment-refractory AA. CONCLUSION: These consensus criteria can help clinicians accurately diagnose AA, provide appropriate treatment, and monitor its progression.

Ganoderma lucidum extract attenuates corticotropin-releasing hormone-induced cellular senescence in human hair follicle cells.

Corticotropin-releasing hormone (CRH) is a key mediator in stress-induced hair growth inhibition. Here, we investigated the impact of stress-induced senescence and evaluated the potential of Ganoderma lucidum (GL) extract in mitigating CRH-induced senescence in human hair follicle cells (hHFCs). We show that CRH treatment increased the senescence-associated beta-galactosidase (SA-ß-GAL) activity and reactive oxygen species (ROS) formation in hHFCs and suppressed alkaline phosphatase (ALP) activity and anagen-inducing genes. However, GL extract restored ALP activity and decreased the expression levels of anagen-related genes in CRH-treated hHFCs. It decreased SA-ß-GAL activity, reduced ROS production, and prevented the phosphorylation of MAPK signaling pathways in CRH-related stress response. Moreover, GL reversed the CRH-induced inhibition of two-cell assemblage (TCA) elongation and Ki67 expression. GL extract attenuates stress-induced hair follicular senescence by delaying catagen entry and scavenging ROS. Our findings suggest that GL extract could be used for treating stress-induced hair loss.

Transpedicular injection of rhBMP-2 with ß-tricalcium phosphate to reduce the proximal junctional kyphosis after adult spinal deformity correction: preliminary study.

The aim of this preliminary study was to assess the impact of injecting recombinant human bone morphogenetic protein-2 (rhBMP-2) with ß-tricalcium phosphate (ß-TCP) carrier into the uppermost instrumented vertebra (UIV) during surgery to prevent the development of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). The 25 patients from study group had received 0.5 mg rhBMP-2 mixed with 1.5 g ß-TCP paste injection into the UIV during surgery. The control group consisted of 75 patients who underwent surgery immediately before the start of the study. The incidences of PJK and PJF were analyzed as primary outcomes. Spinopelvic parameters and patient-reported outcomes were analyzed as secondary outcomes. Hounsfield unit (HU) measurements were performed to confirm the effect of rhBMP-2 with ß-TCP on bone formation at preoperative and postoperative at computed tomography. PJK and PJF was more occurred in control group than study group (p = 0.02, 0.29, respectively). The HU of the UIV significantly increased 6 months after surgery. And the increment at the UIV was also significantly greater than that at the UIV-1 6 months after surgery. Injection of rhBMP-2 with ß-TCP into the UIV reduced PJK and PJF rates 6 months after surgery with new bone formation.

Comparison of Fusion Rates among Various Demineralized Bone Matrices in Posterior Lumbar Interbody Fusion.

Background and Objectives: Posterior lumbar interbody fusion (PLIF) plays a crucial role in addressing various spinal disorders. The success of PLIF is contingent upon achieving bone fusion, as failure can lead to adverse clinical outcomes. Demineralized bone matrix (DBM) has emerged as a promising solution for promoting fusion due to its unique combination of osteoinductive and osteoconductive properties. This study aims to compare the effectiveness of three distinct DBMs (Exfuse®, Bongener®, and Bonfuse®) in achieving fusion rates in PLIF surgery. Materials and Methods: A retrospective review was conducted on 236 consecutive patients undergoing PLIF between September 2016 and February 2019. Patients over 50 years old with degenerative lumbar disease, receiving DBM, and following up for more than 12 months after surgery were included. Fusion was evaluated using the Bridwell grading system. Bridwell grades 1 and 2 were defined as 'fusion', while grades 3 and 4 were considered 'non-fusion.' Clinical outcomes were assessed using visual analog scale (VAS) scores for pain, the Oswestry disability index (ODI), and the European quality of life-5 (EQ-5D). Results: Fusion rates were 88.3% for Exfuse, 94.3% for Bongener, and 87.7% for Bonfuse, with no significant differences. All groups exhibited significant improvement in clinical outcomes at 12 months after surgery, but no significant differences were observed among the three groups. Conclusions: There were no significant differences in fusion rates and clinical outcomes among Exfuse, Bongener, and Bonfuse in PLIF surgery.

Topical minoxidil and dietary supplement for the treatment of chemotherapy-induced alopecia in childhood: a retrospective cohort study.

Chemotherapy-induced alopecia (CIA) is a common and debilitating condition in children, with limited research on its characteristics and treatment. Therefore, this study aims to describe the characteristics of pediatric patients with CIA and the treatment outcomes of topical minoxidil and L-cystine, medicinal yeast, and pantothenic acid complex-based dietary supplements (CYP). This retrospective cohort study analyzed data from patients who underwent high-dose conditioning chemotherapy followed by hematopoietic stem cell transplantation and were treated with either topical minoxidil or CYP for CIA between January 2011 and January 2022. Among the 70 patients evaluated, 61 (87.1%) experienced clinical improvement. Patients in the groups with superior treatment outcomes received a greater cumulative amount of minoxidil and underwent treatment for a more extended duration (P < 0.05) than those in the other groups. All 70 (100%) patients received topical minoxidil, and 42 (60%) were administered CYP. Hair thickness was significantly higher in the combination therapy group than in the minoxidil monotherapy group (21.4% vs. 9.3%, P = 0.02). However, only 3 (4.3%) patients reported mild and self-limiting adverse events. In conclusion, our study shows that minoxidil and CYP administration represent viable treatment options for pediatric CIA.

Endocrine and metabolic comorbidities in primary cicatricial alopecia: A nationwide population-based study.

Primary cicatricial alopecia (PCA) is a rare, scarring, hair loss disorder. Due to its low incidence, little is known about endocrine and metabolic comorbidities in patients with PCA. Thus, we aimed to investigate the association between PCA and endocrine and metabolic disorders. This nationwide, population-based, cross-sectional study included patients diagnosed with PCA or non-cicatricial alopecia (NCA) and normal individuals without history of alopecia registered in the Korean National Health Insurance Service database between January 1, 2011, and December 31, 2020. We calculated the odds ratios of endocrine and metabolic comorbidities of patients with PCA compared to all patients or age- and sex-matched patients with NCA or normal individuals using multivariable logistic regression models. A total of 3 021 483 individuals (mean age [SD], 38.7 [15.0] years, 1 607 380 [53.2%] men), including 11 956 patients with PCA, 601 852 patients with NCA, and 2 407 675 normal participants, were identified. Patients with PCA had an increased risk for dyslipidemia (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.06-1.24), diabetes (aOR 1.38, 95% CI 1.24-1.53), and hypertension (aOR 1.10, 95% CI 1.02-1.19) compared to matched patients with NCA. Regarding PCA subtypes, lichen planopilaris/frontal fibrosing alopecia was positively associated with hypothyroidism (aOR 2.03, 95% CI 1.44-2.86) compared to NCA. Folliculitis decalvans and dissecting cellulitis were positively associated with dyslipidemia (aOR 1.16, 95% CI 1.05-1.28 and aOR 1.16, 95% CI 1.04-1.29, respectively), diabetes (aOR 1.38, 95% CI 1.20-1.58 and aOR 1.52, 95% CI 1.32-1.74, respectively), and hypertension (aOR 1.10, 95% CI 1.00-1.20 and aOR 1.14, 95% CI 1.02-1.27, respectively). Similar trends were observed when each PCA subgroup was compared with the normal control group. This study demonstrates that patients with PCA are more likely to have endocrine and metabolic comorbidities than patients without PCA. Further research on these comorbidities may improve the understanding of PCA.

Single-Cell and Spatial Transcriptome Analysis of Dermal Fibroblast Development in Perinatal Mouse Skin: Dynamic Lineage Differentiation and Key Driver Genes.

Several single-cell RNA studies of developing mouse skin have elucidated the molecular and cellular processes involved in skin development. However, they have primarily focused on either the fetal or early postnatal period, leaving a gap in our understanding of skin development. In this study, we conducted a comprehensive time-series analysis by combining single-cell RNA-sequencing datasets collected at different stages of development (embryonic days 13.5, 14.5, and 16.5 and postnatal days 0, 2, and 4) and validated our findings through multipanel in situ spatial transcriptomics. Our analysis indicated that embryonic fibroblasts exhibit heterogeneity from a very early stage and that the rapid determination of each lineage occurs within days after birth. The expression of putative key driver genes, including Hey1, Ebf1, Runx3, and Sox11 for the dermal papilla trajectory; Lrrc15 for the dermal sheath trajectory; Zfp536 and Nrn1 for the papillary fibroblast trajectory; and Lrrn4cl and Mfap5 for the fascia fibroblast trajectory, was detected in the corresponding, spatially identified cell types. Finally, cell-to-cell interaction analysis indicated that the dermal papilla lineage is the primary source of the noncanonical Wnt pathway during skin development. Together, our study provides a transcriptomic reference for future research in the field of skin development and regeneration.

Activation of mitochondrial aldehyde dehydrogenase 2 promotes hair growth in human hair follicles.

INTRODUCTION: Hair loss is a common phenomenon associated with various environmental and genetic factors. Mitochondrial dysfunction-induced oxidative stress has been recognized as a crucial determinant of hair follicle (HF) biology. Aldehyde dehydrogenase 2 (ALDH2) mitigates oxidative stress by detoxifying acetaldehyde. This study investigated the potential role of ALDH2 modulation in HF function and hair growth promotion. OBJECTIVES: To evaluate the effects of ALDH2 activation on oxidative stress in HFs and hair growth promotion. METHODS: The modulatory role of ALDH2 on HFs was investigated using an ALDH2 activator. ALDH2 expression in human HFs was evaluated through in vitro immunofluorescence staining. Ex vivo HF organ culture was employed to assess hair shaft elongation, while the fluorescence probe 2',7'- dichlorodihydrofluorescein diacetate was utilized to detect reactive oxygen species (ROS). An in vivo mouse model was used to determine whether ALDH2 activation induces anagen. RESULTS: During the anagen phase, ALDH2 showed significantly higher intensity than that in the telogen phase, and its expression was primarily localized along the outer layer of HFs. ALDH2 activation promoted anagen phase induction by reducing ROS levels and enhancing reactive aldehyde clearance, which indicated that ALDH2 functions as a ROS scavenger within HFs. Moreover, ALDH2 activation upregulated Akt/GSK 3ß/ß-catenin signaling in HFs. CONCLUSIONS: Our findings highlight the hair growth promotion effects of ALDH2 activation in HFs and its potential as a promising therapeutic approach for promoting anagen induction.

Clinical Benefits of Baricitinib Therapy According to Scalp Hair Regrowth in Patients with Severe Alopecia Areata.

OBJECTIVES: The present analyses report integrated results from BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) on the clinical benefits of baricitinib treatment on the basis of the amount of scalp hair regrowth through 52 weeks of treatment. METHODS: This post hoc analysis was conducted with data from patients who were treated continuously for 52 weeks with baricitinib 4 mg or 2 mg. Clinical outcomes were assessed using the Severity of Alopecia Tool (SALT) and Clinician-Reported Outcome (ClinRO) for Eyebrow (EB) and Eyelash (EL) hair. Secondary measures included the Hospital Anxiety and Depression Scale and Skindex-16 adapted for alopecia areata. At week 52, patients were classified into three subgroups: SALT ≤ 20 response, intermediate response (achieved a 30% improvement from baseline (SALT30) without a SALT score ≤ 20), or nonresponse (never achieved SALT30). The criterion of SALT30 approximates a minimal clinical meaningful response to therapy. RESULTS: At week 52, with baricitinib 4 mg treatment, the greatest (70%) improvement in EB and EL was observed in responders, but approximately 50% of patients with intermediate response and 20% of nonresponders experienced complete/nearly complete EB and EL regrowth. Improvement in emotional distress was directionally related to improvements in scalp hair regrowth, while impact on quality of life was proportionately greater for the responder subgroup. CONCLUSIONS: Clinically meaningful regrowth in eyebrow and eyelash hair can occur in the absence of complete scalp hair regrowth after treatment with baricitinib. Emotional distress and quality of life improvement is most associated with obtaining a clinical meaningful improvement in scalp hair. TRIAL REGISTRATION NUMBER: BRAVE-AA1, ClinicalTrials.gov number, NCT03570749, start date, 24 September 2018; BRAVE-AA2, ClinicalTrials.gov number, NCT03899259, start date, 8 July 2019.

Design of auditory P300-based brain-computer interfaces with a single auditory channel and no visual support.

Non-invasive brain-computer interfaces (BCIs) based on an event-related potential (ERP) component, P300, elicited via the oddball paradigm, have been extensively developed to enable device control and communication. While most P300-based BCIs employ visual stimuli in the oddball paradigm, auditory P300-based BCIs also need to be developed for users with unreliable gaze control or limited visual processing. Specifically, auditory BCIs without additional visual support or multi-channel sound sources can broaden the application areas of BCIs. This study aimed to design optimal stimuli for auditory BCIs among artificial (e.g., beep) and natural (e.g., human voice and animal sounds) sounds in such circumstances. In addition, it aimed to investigate differences between auditory and visual stimulations for online P300-based BCIs. As a result, natural sounds led to both higher online BCI performance and larger differences in ERP amplitudes between the target and non-target compared to artificial sounds. However, no single type of sound offered the best performance for all subjects; rather, each subject indicated different preferences between the human voice and animal sound. In line with previous reports, visual stimuli yielded higher BCI performance (average 77.56%) than auditory counterparts (average 54.67%). In addition, spatiotemporal patterns of the differences in ERP amplitudes between target and non-target were more dynamic with visual stimuli than with auditory stimuli. The results suggest that selecting a natural auditory stimulus optimal for individual users as well as making differences in ERP amplitudes between target and non-target stimuli more dynamic may further improve auditory P300-based BCIs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-022-09901-3.

Evaluating the Efficacy of Water-Soluble Bone Wax (Tableau Wax) in Reducing Blood Loss in Spinal Fusion Surgery: A Randomized, Controlled, Pilot Study.

Background and Objectives: Lumbar decompression with fusion surgery is an effective treatment for spinal stenosis, but critical postoperative hematoma is a concern. Bone wax has been widely used to control bone bleeding but it has some drawbacks. This study aimed to evaluate the efficacy of Tableau wax, a bioabsorbable hemostatic material, in patients undergoing spinal fusion surgery through a pilot study design. Materials and Methods: A total of 31 patients were enrolled in this single-surgeon, single-institution study. The participants underwent transforaminal lumbar interbody fusion surgery and were randomly assigned to the control group (Bone wax) or test group (Tableau wax). Demographic data, pre- and post-operative hemoglobin levels, blood loss volume, surgical time, Oswestry Disability Index, and EQ-5D scores were recorded. Results: The study showed no significant difference in preoperative and postoperative hemoglobin levels, Oswestry Disability Index, and EQ-5D scores between the groups. However, the Tableau wax group had a significantly lower reduction in hemoglobin levels (1.3 ± 1.0 g/dL) and blood loss (438.2 mL) compared to the Bone wax group (2.2 ± 0.9 g/dL and 663.1 mL, respectively; p = 0.018 and p = 0.022).

Recurrent Vascularizing Keratitis in Infants With Hereditary Mucoepithelial Dysplasia Related to SREBF1 Mutation.

PURPOSE: This study aims to present ophthalmic manifestations of 2 infants with hereditary mucoepithelial dysplasia (HMD) related to SREBF1 mutation over a 5-year period. METHODS: Two female infants with an unremarkable perinatal history were evaluated for photophobia that had been manifest since 3 months after birth and diffuse scalp alopecia. Complete ocular examinations under anesthesia were performed, as well as genetic and systemic workup. RESULTS: Both patients had vascularizing keratitis in both eyes, characterized by the growth of corneal new vessels from the 360 degrees periphery to the center and the formation of stromal leucomatous opacity at the leading edge. The keratitis partially regressed in response to topical corticosteroids and waxed and waned during the 5 years of follow-up. In addition, the loss of scalp hair developed in a cyclical pattern, causing diffuse scalp alopecia in the patients. Rheumatologic, nutritional, and developmental evaluations were within normal ranges. Whole-exome sequencing identified a heterozygous c.1669C>T (p.Arg557Cys) pathogenic variant in the SREBF1 gene associated with HMD in both patients. CONCLUSIONS: In pediatric patients with recurrent vascularizing keratitis and diffuse scalp alopecia starting early in life, HMD should be considered, and genetic tests and collaboration with dermatologists and pediatricians on the diagnosis should be provided.

Poster Session: Investigating temporal evolutions of perceptual choice within biological and artificial neural networks.

Perceptual decisions involve a process that evolves over time until it reaches a decision boundary. It's important to understand how this process unfolds. Recent psychophysical data indicates that the visual system extracts motion axis information faster than motion direction information (Kwon et al., 2015, J Vision). To understand the underlying mechanisms, we developed a biophysically realistic cortical network model of decision making. We generalized the two-variable reduced spiking neural network (Wong et al., 2006, J Neuroscience) to four-variable. The network input is based on motion energy (Adelson et al., 1985, Josa a) and the temporal profile of surround influence (Tadin et al., 2006, J Neuroscience). The model reproduces the prior experimental findings, showing the motion axis extraction before direction extraction. It reveals a stronger axis-wise inhibitory connection between the selective neural populations than the direction-wise inhibitory connection. We further designed a recurrent deep neural network to validate the neural population connectivity pattern. Our model provides a quantitative explanation for the temporal evolution of motion direction judgments. The results show that the spatiotemporal filtering for visual motion integration, the center-surround antagonism, and stronger axis-wise inhibitory connection between the selective neural populations can explain how the visual system can extract motion axis orientation before detecting motion direction.

An event-termination cue causes perceived time to dilate.

The perceived duration of time does not veridically reflect the physical duration but is distorted by various factors, such as the stimulus magnitude or the observer's emotional state. Here, we showed that knowledge about an event's termination time is another significant factor. We often experience time passage differently when we know that an event will terminate soon. To quantify this, we asked 33 university students to report a rotating clock hand's duration with or without a termination cue that indicated the position at which the clock hand disappeared. The results showed that the presence of the termination cue dilated perceived durations, and the dilating effect was larger when the stimulus duration was longer, or the speed of the rotating stimulus was slower. A control experiment with a start-cue excluded the possibility that the cue's mere existence caused the results. Further computational analyses based on the attention theory-of-time perception revealed that the size of dilation is best explained by neither an event's duration nor the distance traveled by the clock hand, but by how long the clock hand spends time near the termination cue. The results imply that an event-termination cue generates a field in which the perceived time dilates.

Efficacy and safety of ritlecitinib in adolescents with alopecia areata: Results from the ALLEGRO phase 2b/3 randomized, double-blind, placebo-controlled trial.

BACKGROUND/OBJECTIVES: This subgroup analysis of the ALLEGRO phase 2b/3 trial (NCT03732807) evaluated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, for the treatment of alopecia areata (AA) in patients aged 12-17 years. METHODS: In ALLEGRO-2b/3, patients aged ≥12 years with AA and ≥50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (±4-week 200-mg loading dose) or 10 mg or placebo for 24 weeks. In a subsequent 24-week extension period, ritlecitinib groups continued their doses, and patients initially assigned to placebo switched to 200/50 or 50 mg daily. Clinician- and patient-reported hair regrowth outcomes and safety were assessed. RESULTS: In total, 105 adolescents were randomized. At Week 24, 17%-28% of adolescents achieved a Severity of Alopecia Tool (SALT) score ≤20 (≤20% scalp without hair) in the ritlecitinib 30 mg and higher treatment groups versus 0% for placebo. At Week 48, 25%-50% of patients had a SALT score ≤20 across ritlecitinib treatment groups (30 mg and higher). Adolescents reporting that their AA "moderately" or "greatly" improved were 45%-61% in the ritlecitinib groups (30 mg and higher) (vs. 10%-22% for placebo) at Week 24 and 44%-80% at Week 48. The most common adverse events in adolescents were headache, acne, and nasopharyngitis. No deaths, major adverse cardiovascular events, malignancies, pulmonary embolisms, opportunistic infections, or herpes zoster infections were reported. CONCLUSION: Ritlecitinib treatment demonstrated clinician-reported efficacy, patient-reported improvement, and an acceptable safety profile through Week 48 in adolescents with AA with ≥50% scalp hair loss.

Cortical representation of musical pitch in event-related potentials.

Neural coding of auditory stimulus frequency is well-documented; however, the cortical signals and perceptual correlates of pitch have not yet been comprehensively investigated. This study examined the temporal patterns of event-related potentials (ERP) in response to single tones of pitch chroma, with an assumption that these patterns would be more prominent in musically-trained individuals than in non-musically-trained individuals. Participants with and without musical training (N = 20) were presented with seven notes on the C major scale (C4, D4, E4, F4, G4, A4, and B4), and whole-brain activities were recorded. A linear regression analysis between the ERP amplitude and the seven notes showed that the ERP amplitude increased or decreased as the frequency of the pitch increased. Remarkably, these linear correlations were anti-symmetric between the hemispheres. Specifically, we found that ERP amplitudes of the left and right frontotemporal areas decreased and increased, respectively, as the pitch frequency increased. Although linear slopes were significant in both groups, the musically-trained group exhibited marginally steeper slope, and their ERP amplitudes were most discriminant for frequency of tone of pitch at earlier latency than in the non-musically-trained group (~ 460 ms vs ~ 630 ms after stimulus onset). Thus, the ERP amplitudes in frontotemporal areas varied according to the pitch frequency, with the musically-trained participants demonstrating a wider range of amplitudes and inter-hemispheric anti-symmetric patterns. Our findings may provide new insights on cortical processing of musical pitch, revealing anti-symmetric processing of musical pitch between hemispheres, which appears to be more pronounced in musically-trained people. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00274-y.