EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics.

Epidermal growth factor receptor (EGFR) regulates many crucial cellular programs, with seven different activating ligands shaping cell signaling in distinct ways. Using crystallography and other approaches, we show how the EGFR ligands epiregulin (EREG) and epigen (EPGN) stabilize different dimeric conformations of the EGFR extracellular region. As a consequence, EREG or EPGN induce less stable EGFR dimers than EGF-making them partial agonists of EGFR dimerization. Unexpectedly, this weakened dimerization elicits more sustained EGFR signaling than seen with EGF, provoking responses in breast cancer cells associated with differentiation rather than proliferation. Our results reveal how responses to different EGFR ligands are defined by receptor dimerization strength and signaling dynamics. These findings have broad implications for understanding receptor tyrosine kinase (RTK) signaling specificity. Our results also suggest parallels between partial and/or biased agonism in RTKs and G-protein-coupled receptors, as well as new therapeutic opportunities for correcting RTK signaling output.

Structure-based design of a soluble human cytomegalovirus glycoprotein B antigen stabilized in a prefusion-like conformation.

Human cytomegalovirus (HCMV) glycoprotein B (gB) is a class III membrane fusion protein required for viral entry. HCMV vaccine candidates containing gB have demonstrated moderate clinical efficacy, but no HCMV vaccine has been approved. Here, we used structure-based design to identify and characterize amino acid substitutions that stabilize gB in its metastable prefusion conformation. One variant containing two engineered interprotomer disulfide bonds and two cavity-filling substitutions (gB-C7), displayed increased expression and thermostability. A 2.8 Å resolution cryoelectron microscopy structure shows that gB-C7 adopts a prefusion-like conformation, revealing additional structural elements at the membrane-distal apex. Unlike previous observations for several class I viral fusion proteins, mice immunized with postfusion or prefusion-stabilized forms of soluble gB protein displayed similar neutralizing antibody titers, here specifically against an HCMV laboratory strain on fibroblasts. Collectively, these results identify initial strategies to stabilize class III viral fusion proteins and provide tools to probe gB-directed antibody responses.

Prefusion stabilization of the Hendra and Langya virus F proteins.

Nipah virus (NiV) and Hendra virus (HeV) are pathogenic paramyxoviruses that cause mild-to-severe disease in humans. As members of the Henipavirus genus, NiV and HeV use an attachment (G) glycoprotein and a class I fusion (F) glycoprotein to invade host cells. The F protein rearranges from a metastable prefusion form to an extended postfusion form to facilitate host cell entry. Prefusion NiV F elicits higher neutralizing antibody titers than postfusion NiV F, indicating that stabilization of prefusion F may aid vaccine development. A combination of amino acid substitutions (L104C/I114C, L172F, and S191P) is known to stabilize NiV F in its prefusion conformation, although the extent to which substitutions transfer to other henipavirus F proteins is not known. Here, we perform biophysical and structural studies to investigate the mechanism of prefusion stabilization in F proteins from three henipaviruses: NiV, HeV, and Langya virus (LayV). Three known stabilizing substitutions from NiV F transfer to HeV F and exert similar structural and functional effects. One engineered disulfide bond, located near the fusion peptide, is sufficient to stabilize the prefusion conformations of both HeV F and LayV F. Although LayV F shares low overall sequence identity with NiV F and HeV F, the region around the fusion peptide exhibits high sequence conservation across all henipaviruses. Our findings indicate that substitutions targeting this site of conformational change might be applicable to prefusion stabilization of other henipavirus F proteins and support the use of NiV as a prototypical pathogen for henipavirus vaccine antigen design.IMPORTANCEPathogenic henipaviruses such as Nipah virus (NiV) and Hendra virus (HeV) cause respiratory symptoms, with severe cases resulting in encephalitis, seizures, and coma. The work described here shows that the NiV and HeV fusion (F) proteins share common structural features with the F protein from an emerging henipavirus, Langya virus (LayV). Sequence alignment alone was sufficient to predict which known prefusion-stabilizing amino acid substitutions from NiV F would stabilize the prefusion conformations of HeV F and LayV F. This work also reveals an unexpected oligomeric interface shared by prefusion HeV F and NiV F. Together, these advances lay a foundation for future antigen design targeting henipavirus F proteins. In this way, Nipah virus can serve as a prototypical pathogen for the development of protective vaccines and monoclonal antibodies to prepare for potential henipavirus outbreaks.

Distinctive features of the respiratory syncytial virus priming loop compared to other non-segmented negative strand RNA viruses.

De novo initiation by viral RNA-dependent RNA polymerases often requires a polymerase priming residue, located within a priming loop, to stabilize the initiating NTPs. Polymerase structures from three different non-segmented negative strand RNA virus (nsNSV) families revealed putative priming loops in different conformations, and an aromatic priming residue has been identified in the rhabdovirus polymerase. In a previous study of the respiratory syncytial virus (RSV) polymerase, we found that Tyr1276, the L protein aromatic amino acid residue that most closely aligns with the rhabdovirus priming residue, is not required for RNA synthesis but two nearby residues, Pro1261 and Trp1262, were required. In this study, we examined the roles of Pro1261 and Trp1262 in RNA synthesis initiation. Biochemical studies showed that substitution of Pro1261 inhibited RNA synthesis initiation without inhibiting back-priming, indicating a defect in initiation. Biochemical and minigenome experiments showed that the initiation defect incurred by a P1261A substitution could be rescued by factors that would be expected to increase the stability of the initiation complex, specifically increased NTP concentration, manganese, and a more efficient promoter sequence. These findings indicate that Pro1261 of the RSV L protein plays a role in initiation, most likely in stabilizing the initiation complex. However, we found that substitution of the corresponding proline residue in a filovirus polymerase had no effect on RNA synthesis initiation or elongation. These results indicate that despite similarities between the nsNSV polymerases, there are differences in the features required for RNA synthesis initiation.

Targeted HIV Self-Testing Identifies Persons with Undiagnosed HIV and Active Engagement Links them to Care: The GetaKit Study.

Current international HIV testing guidelines recommend that HIV negative persons from HIV priority groups complete repeat screening every 3-6 months; local guidelines in our jurisdiction recommend that such retesting should occur every 3 months. Such an approach allows for timely HIV diagnosis and linkage to care - and aligns with the UNAIDS 95-95-95 targets to have 95% of undiagnosed persons be aware of their HIV status. To meet these aims, new approaches to HIV testing have been developed, including our HIV self-testing initiative, GetaKit.ca, which uses an online screening algorithm to determine eligibility and has built in pathways for re-test reminders, linkage HIV prevention care, and rapid follow-up for positive test results. To understand self-testing frequency in relation to our local recommendations for resting every 3 months, we evaluated data from participants who ordered repeat HIV self-tests through GetaKit.ca. Descriptive analyses were performed on participant characteristics and chi-square tests were performed on aggregated participant risk data. During the study period, 5235 HIV self-tests were distributed to 3627 participants, of whom, 26% ordered more than once and 27% belonged to an HIV priority population. Participants who retested were more likely to have been white, male, and part of an HIV priority population; they were also more likely to have completed prior STI or HIV testing or had a prior STI diagnosis, compared to those who did not. We identified 16 new HIV diagnoses, 2 of which were among repeat testers. Our results suggest that HIV self-testing can be useful to help meet UNAIDS targets to identify undiagnosed infections; however, such efforts are less likely to be successful without adequate linkage to follow-up services, including HIV treatment and prevention care.

Real world outcomes of distributing Lucira Check-It® COVID self-tests in Ontario, Canada: the GetaKit COVID study.

BACKGROUND: In Ontario, Canada we developed and implemented an online screening algorithm for the distribution of HIV self-tests, known as GetaKit. During the COVID pandemic, we adapted the GetaKit algorithm to screen for COVID based on population and infection data and distributed COVID rt-LAMP self-tests (using the Lucira Check-It®) to eligible participants. METHODS: GetaKit/COVID was a prospective observational study that occurred over a 7-month period from September 2021 to April 2022. All potential participants completed an online registration and risk assessment, including demographic information, COVID symptoms and risk factors, and vaccination status. Bivariate comparisons were performed for three outcomes: results reporting status, vaccination status, and COVID diagnosis status. Data were analysed using Chi-Square for categorial covariates and Independent Samples T-Test and Mann-Whitney U test for continuous covariates. Bivariate logistic regression models were applied to examine associations between the covariates and outcomes. RESULTS: During the study period, we distributed 6469 COVID self-tests to 4160 eligible participants; 46% identified as Black, Indigenous or a Person of Colour (BIPOC). Nearly 70% of participants reported their COVID self-test results; 304 of which were positive. Overall, 91% also reported being vaccinated against COVID. Statistical analysis found living with five or fewer people, having tested for COVID previously, and being fully vaccinated were positive factors in results reporting. For COVID vaccination, people from large urban centers, who identified their ethnicity as white, and who reported previous COVID testing were more likely to be fully vaccinated. Finally, being identified as a contact of someone who had tested positive for COVID and the presence of COVID-related symptoms were found to be positive factors in diagnosis. CONCLUSIONS: While most participants who accessed this service were vaccinated against COVID and the majority of diagnoses were identified in participants who had symptoms of, or an exposure to, COVID, our program was able to appropriately link participants to recommended follow-up based on reported risks and results. These findings highlight the utility of online screening algorithms to provide health services, particularly for persons with historical barriers to healthcare access, such as BIPOC or lower-income groups.

Adverse events associated with anastomotic coupling devices in microvascular reconstruction.

OBJECTIVE: In light of the recent US Food and Drug Administration (FDA) Class 2 safety recall notice for anastomotic coupling devices, it is important to understand related adverse events. The aim of this study was to characterize adverse events in anastomotic coupling devices for microvascular reconstruction. METHODS: A retrospective cross-sectional analysis using the 2011 to 2021 US FDA Manufacturer and User Facility Device Experience (MAUDE) database. All reports of adverse events involving anastomotic coupling devices were retrieved from the MAUDE database. Descriptive statistics were used to analyze categorized events. RESULTS: There were a total of 293 documented adverse events related to anastomotic coupling devices. These adverse events resulted in 91 (31.1 %) patient injuries and 239 (81.6 %) device malfunctions. The most frequent patient problems were thrombosis/hematoma (n = 38; 41.8 %), unspecified injury (n = 31; 34.1 %), and failure to anastomose (n = 13; 14.3 %). Free flap necrosis was reported in 42 % of thrombosis/hematoma cases (n = 16). The most common malfunctions were devices operating differently than expected (n = 74; 31.0 %), connection problems (n = 41; 17.2 %), and twisted/bent material (n = 19; 7.9 %). There was no significant trend in the number of adverse events over the study period (p > 0.05). CONCLUSIONS: Adverse events from anastomotic coupling devices represent an important and modifiable factor in free tissue failure. Adverse events are predominately related to devices operating differently than expected and may result in vascular compromise of the free flap. Reconstructive surgeons should be cognizant of defective anastomotic coupling devices and be prepared to utilize traditional hand-sewn anastomosis.

Approach to sexually transmitted infection testing for men who have sex with men.

OBJECTIVE: To provide a guide on appropriate sexually transmitted infection (STI) testing for primary care providers to use with patients who identify as men who have sex with men (MSM). SOURCES OF INFORMATION: Canadian guidelines for STI testing and enteric and protozoan infections; Ontario guidelines for HIV screening and mpox; and US guidelines for STI testing. MAIN MESSAGE: Across Canada rates of sexually transmitted bacterial, enteric, protozoan, and systemic infections-including HIV and mpox-have been steadily increasing among cisgender and transgender MSM. Despite often having similar clinical presentations, these infections have different incubation periods and testing approaches and must be ruled out effectively to guide diagnosis and treatment for MSM-identifying patients who present with symptoms of various conditions. Clinical information and screening recommendations, however, are often found in multiple guidelines rather than in a single source, thus further complicating these clinical encounters. This document provides a consolidated set of evidence and recommendations for STI testing in MSM. CONCLUSION: Testing approaches for STIs should be comprehensive and based on the patient's reported risk factors and clinical presentation. Where ongoing STI risk is identified and negative laboratory test results are received, MSM should also be counselled on recommendations for repeat screening and HIV prevention services, such as preexposure prophylaxis.

The experiences of people who use injection drugs with accessing hepatitis c testing and diagnosis in western countries: A scoping review.

BACKGROUND: The purpose of this scoping review was to summarize the literature that reported on the experiences of people who use injection drugs' access to hepatitis C testing and diagnosis in Western countries. METHODS: The initial search was conducted in 2020 and an updated review was completed in 2022. Seven electronic databases were searched using a peer-reviewed search strategy and included: full-text, peer-reviewed studies with people who inject(ed) drugs, hepatitis C testing or diagnosis, conducted in Western countries. Excluded were studies published prior to 2014 and intervention studies. Two-step screening was conducted in duplicate. Conventional content analysis was used. RESULTS: Six studies were found from the search. The studies were published between 2014 and 2021 in Australia, United Kingdom, and United States. A total of 19 participant characteristics were extracted to contextualize their experiences, demonstrating a lack of demographic data. Four themes were found: Awareness and Knowledge, Stigma, Healthcare Service, and Psychological Responses. There were 58 occurrences of client quotes where participants described their experiences, 29 occurrences of quotes describing client-identified barriers, and 14 occurrences of quotes describing client-identified facilitators. CONCLUSION: A scoping review was conducted to present the experiences, barriers, and facilitators of people who use injection drugs to hepatitis C testing. The lack of demographic data and connection to client quotes further exacerbates the inequities among the population by overlooking their intragroup identities. Understanding their experiences of accessing hepatitis C testing and collecting demographic data will help advance health policies and interventions targeting people who use injection drugs.

Lefebvre's production of space: Implications for nursing.

In this paper, we argue that nurses need to be aware of how the production of space in specific contexts - including health care systems and research institutions - perpetuates marginalized populations' state of social otherness. Lefebvre's idea regarding spatial triad is mobilized in this paper, as it pertains to two-spirited, lesbian, gay, bisexual, trans and queer populations (2SLGBTQ*). We believe that nurses can create counter-spaces within health care systems and research institutions that challenge normative discourses. Lefebvre's work provides us the necessary tools to understand how various places or environments produce identities. In understanding Lefebvre's principles, we believe that nurses can play an essential role in creating counter-spaces, thereby instigating counter-institutional practices, for those who experience otherness.

Activity of EGFR transmembrane region variants indicates specific transmembrane dimers are not required for EGFR activity.

The Epidermal Growth Factor Receptor (EGFR) is a Receptor Tyrosine Kinase that mediates cell proliferation and differentiation events during development and maintenance of complex organisms. Formation of specific, ligand-dependent EGFR dimers is a key step in stimulating EGFR signaling, and crystal structures of active, dimeric forms of isolated EGFR extracellular regions and kinase domains have revealed much about how dimer interactions regulate EGFR activity. The nature and role of the transmembrane region in regulating EGFR activity remains less clear, however. Proposed roles for the transmembrane region range from nonspecific but energetically favorable interactions to specific transmembrane dimer conformations being associated with active, inactive, or activity-modulated states of EGFR. To investigate the role of specific transmembrane dimers in modulating EGFR activity we generated thirteen EGFR variants with altered transmembrane sequences designed to favor or disfavor specific types of transmembrane region interactions. We show using FRET microscopy that EGFR transmembrane regions have an intrinsic propensity to associate in mammalian cell membranes that is counteracted by the extracellular region. We show using cell-based assays that each of the EGFR transmembrane variants except the Neu variant, which results in constitutive receptor phosphorylation, is able to autophosphorylate and stimulate phosphorylation of downstream effectors Erk and Akt. Our results indicate that many transmembrane sequences, including polyleucine, are compatible with EGFR activity and provide no evidence for specific transmembrane dimers regulating EGFR function.

First-time testers in the GetaKit study: conceptualizing new paths to care for gbMSM.

When analyzing the data for Ontario, Canada, HIV rates continue to be highest among gay, bisexual and other men who have sex with men (gbMSM). Since HIV diagnosis is a key component of HIV care, self-testing has provided options for allowing this population to access care, resulting in a significant number of first-time testers. Between 1 April 2021 and 31 January 2022, 882 gbMSM participants ordered an HIV self-test through GetaKit. Of these, 270 participants reported that they had never undergone HIV testing previously. Our data showed that first-time testers were generally younger, members of BIPOC (Black, Indigenous and people of color) communities and they reported more invalid test results than those who had tested previously. This suggests that HIV self-testing may be a more successful and appealing component of the HIV prevention armamentarium for this population, but one that is not without its shortcomings as an entry to care.

Safer opioid supply: qualitative program evaluation.

BACKGROUND: As the overdose crisis in Canada continues to escalate in severity, novel interventions and programs are required. Safer Supply programs offer pharmaceutical-grade medication to people who use drugs to replace and decrease harms related to the toxic illicit drug supply. Given the paucity of research surrounding these programs, we sought to better understand the experience of being part of a Safer Supply program from the perspective of current participants. METHODS: We completed semi-structured interviews and surveys with Safer Supply participants in Ottawa, Canada. Interviews were audio-recorded, transcribed, and analyzed thematically. Descriptive statistics were used to report survey data. RESULTS: Participants most commonly discussed Safer Supply benefits. This included programs offering a sense of community, connection, hope for the future, and increased autonomy. Participants also described program concerns, such as restrictive protocols, inadequate drugs, and diversion. CONCLUSIONS: Our research demonstrated that participants found Safer Supply to be effective and impactful for their substance use goals. While participants did discuss concerns about the program, overall, we found that this is an important harm reduction-based program for people who use drugs in the midst of the overdose crisis.

HIV self-testing enabled access to testing for Black persons: The GetaKit study.

In Ontario, new HIV diagnoses continue to affect gay, bisexual, and other men who have sex with men (gbMSM) and persons of African, Caribbean, or Black (ACB) ethnicities. Because treatment and suppressed viral loads flow from diagnosis, testing is key. We sought to determine the outcomes of online ordering and mail-out of free at-home HIV self-testing in Ontario, Canada. We implemented the GetaKit study to offer such free HIV self-testing using the INSTI® test and offered it via a website (GetaKit.ca) to eligible persons in Ontario. From April 1, 2021 to January 31, 2022, we distributed kits to 1551 persons; 40% were white and 26% were ACB. We found that ACB participants were less likely to fulfill established criteria for HIV PrEP, such as previous sexually transmitted infections diagnoses and drug use, despite having a similar test positivity rate. We also found that ACB women, who may represent a larger number of new infections than previously thought, did not have a higher rate of first-time testing. Our results suggest that HIV self-testing can enable testing, but that work is required to increase uptake among ACB persons and women. Overall, HIV self-testing thus corresponded with increased testing among persons who were Black, yet lower rates of results reporting. Patient or Public Contributions: Community members from the AIDS Committee of Ottawa, Max Ottawa, and Black Cap, and nurses from Ottawa Public Health were involved in the design, promotion, and implementation of this study.

Intellectual Property in Facial Plastic and Reconstructive Surgery: The Importance and Process of Obtaining Intellectual Property Rights.

Understanding the purpose and process of obtaining intellectual property rights (IPR) is fundamental to health care innovation. Facial plastic and reconstructive surgeons are natural innovators; however, knowledge deficit in this space may hinder the ability to move ideas from the "bench to bedside." Here we provide an overview of IPR, outlining the steps necessary to obtain intellectual property protection in an academic setting while highlighting recent U.S. Food and Drug Administration (FDA) approvals pertaining to facial plastic and reconstructive surgery.

Genome-Wide Association Study and Genomic Prediction of Fusarium Wilt Resistance in Common Bean Core Collection.

The common bean (Phaseolus vulgaris L.) is a globally cultivated leguminous crop. Fusarium wilt (FW), caused by Fusarium oxysporum f. sp. phaseoli (Fop), is a significant disease leading to substantial yield loss in common beans. Disease-resistant cultivars are recommended to counteract this. The objective of this investigation was to identify single nucleotide polymorphism (SNP) markers associated with FW resistance and to pinpoint potential resistant common bean accessions within a core collection, utilizing a panel of 157 accessions through the Genome-wide association study (GWAS) approach with TASSEL 5 and GAPIT 3. Phenotypes for Fop race 1 and race 4 were matched with genotypic data from 4740 SNPs of BARCBean6K_3 Infinium Bea Chips. After ranking the 157-accession panel and revealing 21 Fusarium wilt-resistant accessions, the GWAS pinpointed 16 SNPs on chromosomes Pv04, Pv05, Pv07, Pv8, and Pv09 linked to Fop race 1 resistance, 23 SNPs on chromosomes Pv03, Pv04, Pv05, Pv07, Pv09, Pv10, and Pv11 associated with Fop race 4 resistance, and 7 SNPs on chromosomes Pv04 and Pv09 correlated with both Fop race 1 and race 4 resistances. Furthermore, within a 30 kb flanking region of these associated SNPs, a total of 17 candidate genes were identified. Some of these genes were annotated as classical disease resistance protein/enzymes, including NB-ARC domain proteins, Leucine-rich repeat protein kinase family proteins, zinc finger family proteins, P-loopcontaining nucleoside triphosphate hydrolase superfamily, etc. Genomic prediction (GP) accuracy for Fop race resistances ranged from 0.26 to 0.55. This study advanced common bean genetic enhancement through marker-assisted selection (MAS) and genomic selection (GS) strategies, paving the way for improved Fop resistance.

Delivering COVID self-tests through GetaKit.ca: Creating testing access during a pandemic.

OBJECTIVES: To determine the real-world outcomes associated with using the GetaKit.ca website to distribute COVID self-tests to persons with risk factors, with a focus on facilitating testing for persons who are Black, Indigenous, or of Colour (BIPOC). METHODS: GetaKit was an open cohort observational study to distribute free self-tests, starting with HIV self-testings and then adding the Lucira Check-It® COVID self-test. Participants would register on our website and complete a risk assessment, which would calculate their need for each type of testing. RESULTS: Focusing on the COVID self-tests, from September to December 2021 (with targeted outreach in winter 2022), we distributed 6474 COVID self-tests to 3653 persons through 4161 unique orders, of which 47% came from BIPOC participants. Compared to white participants, BIPOC participants were more likely to have been a contact of COVID but less likely to be vaccinated. As well, 69% of results were reported back via the GetaKit.ca website, with 5.3% of these being positive. The positivity rate for our 3653 participants was 9.6%. CONCLUSIONS: Delivering COVID self-tests via our website provided tests to BIPOC communities and yielded positivity rates that matched local COVID testing centres. This highlights the utility of such systems for delivering testing during future pandemics.

Perceptions, motivations, and beliefs about HIV risk and pre-exposure prophylaxis (PrEP) among participants in a nurse-led PrEP service (PrEP-RN).

BACKGROUND: While HIV pre-exposure prophylaxis (PrEP) has become more readily available in Canada, its uptake among HIV priority populations continues to be affected by system-level and individual factors. Such impediments relate to challenges by healthcare providers in assessing HIV-related risk and variability in patients' motivations for PrEP initiation and continued engagement in care. METHODS: In Ottawa, Canada, a group of researchers implemented Canada's first nurse-led HIV prevention program, known as PrEP-RN. As part of this pilot, qualitative interviews were completed with fourteen patients who had accessed PrEP-RN. The purpose of these interviews was to understand participants' perspectives related to HIV prevention and experiences accessing care through a nurse-led service. Interviews were analyzed using thematic analysis, which were organized into the two major themes of (1) motivations for PrEP initiation and (2) beliefs about the benefits of PrEP. RESULTS: Findings revealed participants' motivations for PrEP differed from healthcare provider's views of risk, which were influenced by external life factors and personal perceptions of risk. In addition, participants discussed the benefits of PrEP in terms of its ability to manage their potential mistrust of sexual partners, control their sexual health, and liberate fears and anxieties related to HIV. CONCLUSIONS: Based on these findings, health and allied providers should consider incorporating individual motivations and beliefs into patient education and counselling about PrEP to better target HIV prevention care at persons are at elevated risk of HIV. These perspectives could also be used to re-structure web and social media campaigns to increase PrEP uptake among HIV priority populations.

Identification and validation of a QTL for spikelet number on chromosome arm 6BL of common wheat (Triticum aestivum L.).

To provide food security for a growing world population, it will be necessary to increase yields of staple crops such as wheat (Triticum aestivum L.). Yield is a complex, polygenic trait influenced by grain weight and number, which are negatively correlated with one another. Spikelet number is an important determinant of grain number, but allelic variants impacting its expression are often associated with heading date, constraining their use in wheat germplasm that must be adapted for specific environments. Identification and characterization of genetic variants affecting spikelet number will increase selection efficiency through their deployment in breeding programs. In this study, a quantitative trait locus (QTL) on chromosome arm 6BL for spikelet number was identified and validated using an association mapping panel, a recombinant inbred line population, and seven derived heterogeneous inbred families. The superior allele, QSn.csu-6Bb, was associated with an increase of 0.248 to 0.808 spikelets per spike across multiple environments that varied for mean spikelet number. Despite epistatic interactions between QSn.csu-6B and three other loci (WAPO-A1, VRN-D3, and PPD-B1), genotypes with a greater number of superior alleles at these loci consistently exhibit higher spikelet number. The frequency of superior alleles at these loci varies among winter wheat varieties adapted to different latitudes of the US Great Plains, revealing opportunities for breeders to select for increased spikelet number using simple molecular markers. This work lays the foundation for the positional cloning of the genetic variant underlying the QSn.csu-6B QTL to strengthen our understanding of spikelet number determination in wheat. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01288-7.

Personality, Success, and Beyond: The Layperson's Perception of Patients With Facial Transplantation.

BACKGROUND: While the goal of facial vascularized composite allotransplantation (FVCA) is to provide patients with improved physical and social function, no study has evaluated layperson perception of social acceptance and perceived career success of patients with FVCA. The purpose of this study was to determine how FVCA changes social acceptance and perceived career success of patients with facial disfiguration. METHODS: Eight hundred fifteen laypersons were surveyed through Mechanical Turk to evaluate their perceptions of patients with FVCA. Respondents were shown facial photographs of patients pre-FVCA, post-FVCA, and matched controls and evaluated these photos on 26 items of perceived social acceptance and career success. Responses were analyzed using descriptive statistics and the Wilcoxon signed-rank test. RESULTS: Both male and female post-FVCA photos were perceived as significantly more socially accepted and professionally successful than their pre-FVCA photos in at least 21 out of 26 items (P < 0.001 for all), but the posttransplant patients scored lower than their control in at least 25 out of 26 items (P < 0.001 for all). Additionally, there were discrepancies in findings based on patient gender. CONCLUSIONS: This study suggests that while FVCA has a significantly positive impact on social acceptance and perceived professional success, it does not fully reinstate these qualities. Furthermore, varying surgical outcomes and/or cognitive biases (such as gender) may impact perceptions of the individual by the public. Our findings suggest a need to standardize practices to better predict and improve outcomes and encourage surgeons to consider patient factors such as gender when planning these procedures.