Meta-Analysis of Validated Quality of Life Outcomes Following Voice Feminization in Transwomen.

OBJECTIVES: For transwomen undergoing voice feminization interventions, fundamental frequency (F 0 ; vocal pitch) is a commonly reported functional outcome measure in the literature. However, F 0 may not correlate well with improvement in quality of life (QoL). Several validated voice-related QoL instruments have been used to assess QoL improvement in these patients, yet there is no consensus on the most appropriate instrument. This systematic review and meta-analysis aimed to assess the relationship between change in F 0 and QoL improvement following voice feminization, and to compare validated QoL instruments commonly used in this population. DATA SOURCES: PubMed, Cochrane, and Embase. REVIEW METHODS: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Primary studies of transwomen undergoing voice feminization, reporting validated QoL outcomes were included. Meta-analyses for associations between mean change in QoL score and mean change in F 0 , as well as variations in mean change in QoL score by QoL instrument, were performed using a multilevel mixed effects model. RESULTS: No statistically significant correlation was found between change in F 0 and QoL score improvement post-intervention. Different validated instruments showed statistically significant variation in QoL score change, with the Trans Women Voice Questionnaire (TWVQ) capturing a greater improvement in QoL score relative to other instruments. CONCLUSIONS: Lack of correlation between changes in F 0 and QoL improvement further supports that F 0 alone is insufficient to assess the efficacy of voice feminizing interventions. Validated QoL measures are useful adjuncts. Of these, the TWVQ appears to be the most sensitive for measurement of QoL improvement following voice feminization.

Systematic Review and Meta-analysis of Facial Anthropometric Variations Among Cisgender Females of Different Ethnicities: Implications for Feminizing Facial Gender Affirming Surgery.

BACKGROUND: Feminizing Facial Gender-Affirming Surgery (FFGAS) is gaining popularity among the diverse population of patients impacted by gender incongruence. However, most studies examining facial femininity are based on Caucasians. Thus, it is unclear if ethnic differences exist in anthropometric measures relevant to FFGAS procedures. This study aims to analyze ethnic anthropometric variations in the cisgender female face to identify differences that are potentially relevant to FFGAS. METHODS: A systematic review and meta-analysis of the PubMed, EMBASE, and Cochrane databases was performed following PRISMA guidelines on June 25, 2021. Original studies reporting facial anthropometry in cisgender women were included. Anthropometric measures of interest included mandibular and zygomatic width, facial and forehead height, and nasolabial angle. A meta-analysis was performed using a linear mixed-effects model for each anthropometric measure. RESULTS: A total of 1246 abstracts were screened, yielding 21 articles that met the inclusion criteria. Facial anthropometric data of 4792 cisgender females of 16 different ethnicities were analyzed. This meta-analysis demonstrated that compared with Caucasian cisgender women, Japanese, Chinese, and Korean cisgender women had a wider mandible (Japanese +20.13 mm [SE 4.43, P <0.001, P value adjusted for multiple comparisons (p-adj)=0.002], Chinese +16.22 mm [SE 4.39, P =0.002, p-adj=0.013]; and Korean +14.46 mm [SE 3.97, P =0.002, p-adj=0.014]). Further, when compared with Caucasian cisgender women, Chinese cisgender women demonstrated a larger zygomatic width, African American cisgender women tended to have smaller nasolabial angles, and Indian and Japanese cisgender women tended to have a smaller and larger facial height, respectively. However, following P value adjustment for multiple comparisons, these differences were not found to be statistically significant. CONCLUSIONS: We found that mandibular width tends to be greater for Japanese and Chinese cisgender women relative to Caucasian cisgender women. This data may be useful in counseling patients during preoperative evaluations ahead of mandibular reduction. No other anthropometric features were found to be significantly different among the ethnic groups studied. This portends that current approaches to FFGAS, which emphasize patient-specific needs and maintenance of a harmonious appearance, may require minimal or no adjustment to account for ethnic facial anthropometric differences.

Recipient Selection Criteria for Facial Transplantation: A Systematic Review.

BACKGROUND: Recipient selection is an important determinant of surgical outcomes in facial transplantation (FT). Appropriately, each FT program develops their own guidelines for recipient selection criteria. Currently, there is no resource to simultaneously assess and identify similarities and differences between these guidelines. Such information could be useful in distinguishing areas of FT that are well understood from those that could benefit from further exploration. METHODS: We performed a systematic review of the scientific literature from inception to June 18, 2021, using Pubmed, Embase, Cochrane Library, and Scopus to identify articles pertaining to recipient selection criteria. Clinical trials were identified through the Clinicaltrials.gov registry. United States and international program websites were reviewed for patient-facing information. RESULTS: Our systematic review yielded 90 suitable articles, 8 clinical trials, and 7 program websites containing the recipient selection criteria of 24 different FT programs. The most reported on recipient criteria were age, positive human immunodeficiency viral status (HIV+), positive hepatitis C viral status, psychosocial stability, and medical compliance. Other criteria were rarely addressed, such as blindness and recipient immune status. CONCLUSIONS: Guidelines among different face transplant programs are changing over time. We found consensus on certain recipient selection criteria, but the majority remain program or surgeon dependent, emphasizing that FT is still an evolving procedure. Although most programs reported on their recipient selection criteria, the rationale was often missing. Further discussion about recipient selection criteria and the reasoning behind employing or changing them will help advance the field.

The Histone Chaperone FACT Induces Cas9 Multi-turnover Behavior and Modifies Genome Manipulation in Human Cells.

Cas9 is a prokaryotic RNA-guided DNA endonuclease that binds substrates tightly in vitro but turns over rapidly when used to manipulate genomes in eukaryotic cells. Little is known about the factors responsible for dislodging Cas9 or how they influence genome engineering. Unbiased detection through proximity labeling of transient protein interactions in cell-free Xenopus laevis egg extract identified the dimeric histone chaperone facilitates chromatin transcription (FACT) as an interactor of substrate-bound Cas9. FACT is both necessary and sufficient to displace dCas9, and FACT immunodepletion converts Cas9's activity from multi-turnover to single turnover. In human cells, FACT depletion extends dCas9 residence times, delays genome editing, and alters the balance between indel formation and homology-directed repair. FACT knockdown also increases epigenetic marking by dCas9-based transcriptional effectors with a concomitant enhancement of transcriptional modulation. FACT thus shapes the intrinsic cellular response to Cas9-based genome manipulation most likely by determining Cas9 residence times.

Evidence for DNA-mediated nuclear compartmentalization distinct from phase separation.

RNA Polymerase II (Pol II) and transcription factors form concentrated hubs in cells via multivalent protein-protein interactions, often mediated by proteins with intrinsically disordered regions. During Herpes Simplex Virus infection, viral replication compartments (RCs) efficiently enrich host Pol II into membraneless domains, reminiscent of liquid-liquid phase separation. Despite sharing several properties with phase-separated condensates, we show that RCs operate via a distinct mechanism wherein unrestricted nonspecific protein-DNA interactions efficiently outcompete host chromatin, profoundly influencing the way DNA-binding proteins explore RCs. We find that the viral genome remains largely nucleosome-free, and this increase in accessibility allows Pol II and other DNA-binding proteins to repeatedly visit nearby DNA binding sites. This anisotropic behavior creates local accumulations of protein factors despite their unrestricted diffusion across RC boundaries. Our results reveal underappreciated consequences of nonspecific DNA binding in shaping gene activity, and suggest additional roles for chromatin in modulating nuclear function and organization.