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Several fully continuous probabilistic genotyping software (PGS) use Markov chain Monte Carlo algorithms (MCMC) to assign weights to different proposed genotype combinations at a locus. Replicate interpretations of the same profile in these software are expected not to produce identical weights and likelihood ratio (LR) values due to the Monte Carlo aspect. This paper reports a detailed precision study under reproducibility conditions conducted as a collaborative exercise across the National Institute of Standards and Technology (NIST), Federal Bureau of Investigation (FBI), and Institute of Environmental Science and Research (ESR). Replicate interpretations generated across the three laboratories used the same input files, software version, and settings but different random number seed and different computers. This work demonstrates that using different computers to analyze replicate interpretations does not contribute to any variations in LR values. The study quantifies the magnitude of differences in the assigned LRs that is only due to run-to-run MCMC variability and addresses the potential explanations for the observed differences., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: People with chronic low back pain (LBP) often demonstrate altered muscle activation with movements that involve the lumbopelvic region and hips., Objective: The purpose of this study was to compare gluteus medius activity during sidelying hip abduction (SHA) and sidelying hip abduction-lateral rotation (SHALR) with and without instruction for lumbopelvic stabilization in people with and without chronic LBP., Methods: A cross-sectional study was conducted recruiting participants with ( n  = 17) and without ( n  = 17) chronic LBP. Gluteus medius activity was recorded with surface electromyography during the performance of SHA and SHALR with and without instructions including the abdominal drawing-in maneuver for lumbopelvic stabilization., Results: For SHA and SHALR, there was a significant main effect for instruction for stabilization indicated by a decrease in gluteus medius activity with instructions ( p  = .001, p  < .001). There was not a significant main effect of chronic LBP on gluteus medius activity between groups for either activity. There was no significant interaction effect of pain and instruction for stabilization with SHA or SHALR., Conclusion: Knowledge of changes in gluteus medius muscle activation patterns with trunk stabilization instruction may help clinicians with assessment of exercise performance to optimize gluteus medius activation.

Background: Breast cancer screening and surgical interventions are often underutilized in the Chinese community. For both Chinese American (CA) and native Chinese (NC) patients, screening rates are well below medical recommendations, which places these patients at risk for late diagnoses and larger tumors. There is also a notable reluctance to breast reconstruction after mastectomy. We investigated the role of sociodemographic and cultural barriers in breast treatment trends among Chinese breast cancer survivors., Methods: A literature search for full-text articles published between 2011 and 2021 was performed using PubMed, The Web of Science, and Embase. The articles that were selected contained information regarding Chinese individuals in the United States or China who had undergone breast cancer screening or diagnosis of breast cancer and received treatment with or without reconstructive surgery., Results: Both patient populations exhibited screening rates that were significantly lower than national recommendations. Of the CA patients, 25% reported never receiving a mammogram, whereas 450 million NCs have been left unscreened despite efforts made by the Chinese government. Misinformation, cultural beliefs, and fear significantly contributed to diminished breast health care among CA and NC women. Fear of recurrence, breast value, community influence, and limited health care resources were found to be the primary drivers of low breast reconstruction uptake., Conclusions: In both NC and CA women, there is a critical need for improved breast health information dissemination and overall quality of care. The findings summarized in this review can guide such efforts., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Across scar studies, there is a lack of dark-skinned individuals, who have a predisposition for keloid formation, altered pigmentation and poorer quality of life (QOL). There is a need for patients of colour to be included in scar scale development and validation. In this study, we evaluate the racial diversity of patients included in the validation of scar assessment scales. A systematic review was conducted for articles reporting on the validation of a scar assessment tool. Racial, ethnic and Fitzpatrick skin type (FST) data were extracted. Fifteen scar scale validation studies were included. Nine of the studies did not mention FST, race or ethnicity of the patients. Two of the studies that reported FST or race information only included White patients or included no FST V/VI patients: mapping assessment of scars (MAPS) and University of North Carolina '4P'. Only four studies included non-White patients or dark-skinned patients in the validation of their scar scale: the modified Vancouver Scar Scale (VSS), modified Patient and Observer Scar Assessment Scale (POSAS), acne QOL and SCAR-Q scales. The patients included in the modified VSS validation were 7% and 13% FST V/VI, 14% African in the modified POSAS and 4.5% FST V/VI in the SCAR-Q. We highlight the severe lack of diversity in scar scale validation, with only 4 out of 15 studies including dark-skinned patients. Given the susceptibility of darker-skinned individuals to have poorer scarring outcomes, it is critical to include patients of colour in the very assessment tools that determine their scar prognosis. Inclusion of patients of colour in scar scale development will improve scar assessment and clinical decision-making., (© 2023 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

Background: There are different types of grafts for rhinoplasty, each with certain advantages and disadvantages. Fresh frozen cadaveric costal allograft (CCA) provides an alternative to rhinoplasties. The aim of this study was to compare the outcomes of fresh frozen CCA and traditional autologous costal cartilage in cosmetic and reconstructive rhinoplasty procedures., Methods: This is a prospective, single-center, nonrandomized, open-label clinical trial. Objective assessment to evaluate warping, resorption, and displacement of the cartilage was achieved by measuring the differences of standardized values (deviation angle, nasofrontal angle, total facial convexity, nasofacial angle, and nasolabial angle) obtained at 6-months and 12-months postoperative follow-up on standard two-dimensional photographs (Δ = ∣measurement 6 - measurement 12 ∣). Subjective assessment was measured by the FACE-Q assessment., Results: Fifty eligible patients between March 2017 and October 2020 were included. The average age was 43.9 ± 16.6 years and the mean follow-up period was 14.8 months. In the control group, the changes (Δ) in the deviation angle and nasolabial angle were greater than in the CCA group ( P < 0.05). In the CCA group, the mean score of satisfaction with nose improved at 6 months and 1 year postoperatively ( P < 0.05). The mean score of satisfaction with nostrils and overall facial appearance also increased in the CCA group at 6 months postoperatively ( P < 0.05). Six patients from the CCA group and 10 patients from the control group experienced postoperative complications., Conclusions: Fresh frozen CCA is a safe and reliable source of rhinoplasty grafts. It is aseptic, readily available, and free of donor site complications., Competing Interests: Dr. Galiano is a consultant for MTF Biologics. This study was supported by MTF Biologics. The other authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Standard methods of mixture analysis involve subjecting a dried crime scene sample to a "bulk" DNA extraction method such that the resulting isolate compromises a homogenized DNA mixture from the individual donors. If, however, instead of bulk DNA extraction, a sufficient number of individual cells from the mixed stain are subsampled prior to genetic analysis then it should be possible to recover highly probative single source, non-mixed scDNA profiles from each of the donors. This approach can detect low DNA level minor donors to a mixture that otherwise would not be identified using standard methods and can also resolve rare mixtures comprising first degree relatives and thereby also prevent the false inclusion of non-donor relatives. This literature landscape review and associated commentary reports on the history and increasing interest in current and potential future applications of scDNA in forensic genomics, and critically evaluates opportunities and impediments to further progress., Competing Interests: No competing interests to disclose., (© 2023 The Author(s).)

Probabilistic genotyping systems are able to analyse complex mixed DNA profiles and show good power to discriminate contributors from non-contributors. However, the abilities of the statistical analyses are still unavoidably bound by the quality of information being analysed. If a profile has a high number of contributors, or a contributor that is present in trace amounts, then the amount of information about those individuals in the DNA profile is limited. Recent work has shown the ability to gain better resolution of the genotypes of contributors to complex profiles using cell subsampling. This is the process of taking many sets of a limited number of cells and individually profiling each set. These 'mini-mixtures' can provide greater information about the genotypes of underlying contributors. In our work we take the resulting profiles from multiple subsamplings of complex DNA profiles in equal amounts and show how testing for, and then assuming, a common DNA donor can further improve the ability to resolve the genotypes of contributors. Using direct cell sub-sampling and statistical analysis software DBLR™, we were able to recover single source profiles of uploadable quality from five out of the six contributors of an equally proportioned mixture. Through the analysis of mixtures in this work we provide a template for carrying out common donor analysis for maximum effect., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Some of the authors of this paper are developers of the software programs STRmix™ and DBLR™, which were used to produce the reported results., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA)., Design: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as "important" or "essential" by ≥80% of participants were retained, and participants could suggest additional domains. In Round 2, participants rated their level of agreement that each domain was essential for evaluating OAMPs: 0 = strongly disagree to 10 = strongly agree. A domain was retained if ≥80% rated it ≥6. In Round 3, participants rated remaining domains using same scale as in Round 2; a domain was recommended as "core" if ≥80% of participants rated it ≥9 and as "optional" if ≥80% rated it ≥7., Results: A total of 178 individuals from 26 countries participated; 85 completed all survey rounds. Only one domain, "ability to participate in daily activities", met criteria for a core domain; 25 domains met criteria for an optional recommendation: 8 Patient Impacts, 5 Implementation Outcomes, 5 Participant Characteristics, 3 OAMP Characteristics and 4 Clinician Characteristics., Conclusion: The ability of patients with OA to participate in daily activities should be evaluated in all OAMPs. Teams evaluating OAMPs should consider including domains from the optional recommended set, with representation from all five categories and based on stakeholder priorities in their local context., (Published by Elsevier Ltd.)

Background: The rise in Botox, fillers, and chemical peel procedures demands transparent online information that discloses all relevant risks and complications. This study assesses the quality of complication disclosure on the most popular cosmetic sites., Methods: The top 50 Google search results for "Botox," "fillers," and "chemical peel" were analyzed for their reporting on relevant complications. Websites were categorized based on their origin. An overall complication, prevention, management, prevalence, and disclaimer score were assigned to each site., Results: A total of 136 websites were analyzed. Of these websites, 31 (22.7%) did not mention any complications or risks associated with the treatment. The most commonly reported complications were bruising (67.0%) for Botox, swelling (79.0%) for fillers, and redness (58%) for chemical peels. The least-reported serious complications were toxin spread effects (31.0%) for Botox, vision loss (23.0%) for fillers, and allergic reaction for chemical peel (18.0%). Reports of serious and rare side effects were significantly lower than those of common side effects (Botox, P = .001; fillers, P = .004; chemical peels, P < .001). The overall mean (standard deviation) complication score across all websites was 2.81/5 (1.31). Online health reference and academic/hospital sites disclosed complications better than sources in most other categories ( P < .001)., Conclusions: The reporting of online complications for the top 3 cosmetic procedures performed in the US is highly variable, biased, and at times, completely absent. Patients pursuing cosmetic surgery are heavily influenced by the internet and vulnerable to misinformation. Cosmetic procedure websites are in need of drastic improvement to ensure the health and safety of all patients., Competing Interests: Disclosures: The authors have no conflict of interest to disclose.

Probabilistic genotyping (PG) and its associated software has greatly aided in forensic DNA mixture analysis, with it primarily being applied to mixed DNA profiles obtained from bulk cellular extracts. However, these software applications do not always result in probative information about the identity of all donors to said mixtures/extracts. This is primarily due to mixture complexity caused by overlapping alleles and the presence of artifacts and minor donors. One way of reducing mixture complexity is to perform direct single cell subsampling of the bulk mixture prior to genotyping and interpretation. The analysis of low template DNA samples, including from single or few cells, has also benefited from the application of PG methods. With the application of PG, multiple cell subsamples originating from the same donor can be combined into a single analysis using the software replicate analysis function often resulting in full DNA profile donor information. In the present work, we demonstrate how two PG software systems, STRmix TM and EuroForMix, were successfully validated for single or few cell applications.

Since Y-STR typing only amplifies male Y chromosomal DNA, it can simplify the interpretation of some DNA mixtures that contain female DNA. However, if there are multiple male contributors, mixed Y-STR DNA profiles will often be obtained. Y-STR mixture analysis cases are particularly challenging though as, currently, there are no validated probabilistic genotyping (PG) software solutions commercially available to aid in their interpretation. One approach to fully deconvoluting these challenging mixtures into their individual donors is to conduct single-cell genotyping by isolating individual cells from a mixture prior to conducting DNA typing. In this work, a physical micromanipulation technique involving a tungsten needle and direct PCR with decreased reaction volume and increased cycle number was applied to equimolar 2- and 3-person buccal cell male DNA mixtures and a mock touch DNA case scenario involving the consecutive firing of a handgun by two males. A consensus DNA profiling approach was then utilized to obtain YFiler™ Plus Y-STR haplotypes. Buccal cells were used to optimize and test the direct single-cell subsampling approach, and 2-3 person male buccal cell mixtures were fully deconvoluted into their individual donor Y-STR haplotypes. Single-cell (or agglomerated cell clump) subsampling from the gun's trigger recovered single-source Y-STR profiles from both individuals who fired the gun, the owner, and the other unrelated male. Only the non-owner's DNA was found in the cells recovered from the handle. In summary, direct single-cell subsampling as described represents a potential simple way to analyze and interpret Y-STR mixtures., (© 2022 American Academy of Forensic Sciences.)

Aim: To evaluate an intravitreally injected nanoparticle platform designed to deliver VEGF-A siRNA to inhibit retinal neovascular leakage as a new treatment for proliferative diabetic retinopathy and diabetic macular edema. Materials & methods: Fusogenic lipid-coated porous silicon nanoparticles loaded with VEGF-A siRNA, and pendant neovascular integrin-homing iRGD, were evaluated for efficacy by intravitreal injection in a rabbit model of retinal neovascularization. Results: For 12 weeks post-treatment, a reduction in vascular leakage was observed for treated diseased eyes versus control eyes (p = 0.0137), with a corresponding reduction in vitreous VEGF-A. Conclusion: Fusogenic lipid-coated porous silicon nanoparticles siRNA delivery provides persistent knockdown of VEGF-A and reduced leakage in a rabbit model of retinal neovascularization as a potential new intraocular therapeutic.

Analysis of complex DNA mixtures comprised of related individuals requires a great degree of care due to the increased risk of falsely including non-donor first-degree relatives. Although alternative likelihood ratio (LR) propositions that may aid in the analysis of these difficult cases can be employed, the prior information required for their use is not always known, nor do these alternative propositions always prevent false inclusions. For example, with a father/mother/child mixture, conditioning the mixture on the presence of one of the parents is recommended. However, the definitive presence of the parent(s) is not always known and an assumption of their presence in the mixture may not be objectively justifiable. Additionally, the high level of allele sharing seen with familial mixtures leads to an increased risk of underestimating the number of contributors (NOC) to a mixture. Therefore, fully resolving and identifying each of the individuals present in familial mixtures and excluding related non-donors is an important goal of the mixture deconvolution process and can be of great investigative value. Here, firstly, we further investigated and confirmed the problems encountered with standard bulk analysis of familial mixtures and demonstrated the ability of single cell analysis to fully distinguish first-degree relatives (FDR). Then, separation of each of the individual donors via single cell analysis was carried out by a combination of direct single cell subsampling (DSCS), enhanced DNA typing, and probabilistic genotyping, and applied to three complex familial 4-person mixtures resulting in a probative gain of LR for all donors and an accurate determination of the NOC. Significantly, non-donor first-degree relatives that were falsely included (LRs > 102−108) by a standard bulk sampling and analysis approach were no longer falsely included using DSCS.

Mutations in the Membrane-type frizzled related protein (Mfrp) gene results in an early-onset retinal degeneration associated with retinitis pigmentosa, microphthalmia, optic disc drusen and foveal schisis. In the current study, a previously characterized mouse model of human retinal degeneration carrying homozygous c.498&#95;499insC mutations in Mfrp (Mfrp KI/KI ) was used. Patients carrying this mutation have retinal degeneration at an early age. The model demonstrates subretinal deposits and develops early-onset photoreceptor degeneration. We observed large subretinal deposits in Mfrp KI/KI mice which were strongly CD68 positive and co-localized with autofluorescent spots. Single cell RNA sequencing of Mfrp KI/KI mice retinal microglia showed a significantly higher number of pan-macrophage marker Iba-1 and F4/80 positive cells with increased expression of activation marker (CD68) and lowered microglial homeostatic markers (TMEM119, P2ry13, P2ry13, Siglech) compared with wild type mice confirming microglial activation as observed in retinal immunostaining showing microglia activation in subretinal region. Trajectory analysis identified a small cluster of microglial cells with activation transcriptomic signatures that could represent a subretinal microglia population in Mfrp KI/KI mice expressing higher levels of APOE. We validated these findings using immunofluorescence staining of retinal cryosections and found a significantly higher number of subretinal Iba-1/ApoE positive microglia in Mfrp KI/KI mice with some subretinal microglia also expressing lowered levels of microglial homeostatic marker TMEM119, confirming microglial origin. In summary, we confirm that Mfrp KI/KI mice carrying the c.498&#95;499insC mutation had a significantly higher population of activated microglia in their retina with distinct subsets of subretinal microglia. Further, studies are required to confirm whether the association of increased subretinal microglia in MfrpKI/KI mice are causal in degeneration., (© 2022. The Author(s).)

When a minor DNA component to a binary mixture is present at a weight ratio of approximately 1:50 or less, the presence of this minor donor is undetectable (or barely detectable) by standard mixture deconvolution approaches. In an attempt to retrieve probative minor donor DNA profile information, multiple quintuple cell subsamples were collected from a 1:50 DNA mixture using direct single cell subsampling (DSCS) paired with probabilistic genotyping (PG), the latter validated for use with single or few cells. DSCS employs a simplified micromanipulation technique paired with an enhanced DNA profiling approach, involving direct cell lysis and a sensitive PCR process, to genotype individual cells. Multiple five-cell subsamples were used to interrogate sufficient cells from the mixture such that some of the created 5-cell "mini-mixture" subsamples contained a cell from the minor donor. The latter mini-mixture subsamples, which now comprised weight ratios of 1:4 as opposed to the bulk mixture 1:50, were analyzed with the PG systems STRmix TM and EuroForMix resulting in a significant probative gain of information, (LR ≅ 10 11 , compared to standard bulk mixture PG methods, LR ≅ 10 1 -10 2 ).

DNA mixtures are a common source of crime scene evidence and are often one of the more difficult sources of biological evidence to interpret. With the implementation of probabilistic genotyping (PG), mixture analysis has been revolutionized allowing previously unresolvable mixed profiles to be analyzed and probative genotype information from contributors to be recovered. However, due to allele overlap, artifacts, or low-level minor contributors, genotype information loss inevitably occurs. In order to reduce the potential loss of significant DNA information from donors in complex mixtures, an alternative approach is to physically separate individual cells from mixtures prior to performing DNA typing thus obtaining single source profiles from contributors. In the present work, a simplified micro-manipulation technique combined with enhanced single-cell DNA typing was used to collect one or few cells, referred to as direct single-cell subsampling (DSCS). Using this approach, single and 2-cell subsamples were collected from 2 to 6 person mixtures. Single-cell subsamples resulted in single source DNA profiles while the 2-cell subsamples returned either single source DNA profiles or new mini-mixtures that are less complex than the original mixture due to the presence of fewer contributors. PG (STRmix™) was implemented, after appropriate validation, to analyze the original bulk mixtures, single source cell subsamples, and the 2-cell mini mixture subsamples from the original 2-6-person mixtures. PG further allowed replicate analysis to be employed which, in many instances, resulted in a significant gain of genotype information such that the returned donor likelihood ratios (LRs) were comparable to that seen in their single source reference profiles (i.e., the reciprocal of their random match probabilities). In every mixture, the DSCS approach gave improved results for each donor compared to standard bulk mixture analysis. With the 5- and 6- person complex mixtures, DSCS recovered highly probative LRs (≥10 20 ) from donors that had returned non-probative LRs (<10 3 ) by standard methods., (Copyright © 2022 The Chartered Society of Forensic Sciences. Published by Elsevier B.V. All rights reserved.)

HER2+ breast cancer patients are presented with either synchronous (S-BM), latent (Lat), or metachronous (M-BM) brain metastases. However, the basis for disparate metastatic fitness among disseminated tumor cells of similar oncotype within a distal organ remains unknown. Here, employing brain metastatic models, we show that metabolic diversity and plasticity within brain-tropic cells determine metastatic fitness. Lactate secreted by aggressive metastatic cells or lactate supplementation to mice bearing Lat cells limits innate immunosurveillance and triggers overt metastasis. Attenuating lactate metabolism in S-BM impedes metastasis, while M-BM adapt and survive as residual disease. In contrast to S-BM, Lat and M-BM survive in equilibrium with innate immunosurveillance, oxidize glutamine, and maintain cellular redox homeostasis through the anionic amino acid transporter xCT. Moreover, xCT expression is significantly higher in matched M-BM brain metastatic samples compared to primary tumors from HER2+ breast cancer patients. Inhibiting xCT function attenuates residual disease and recurrence in these preclinical models., Competing Interests: Declaration of interests A.B.H. has received research grant support from Takeda and travel support from Puma Biotechnology. C.L.A. receives or has received research grant support from Pfizer, Lilly, and Takeda; holds stock options in Provista and Y-TRAP; and serves or has served in an advisory role to Novartis, Lilly, TAIHO Oncology, Daiichi Sankyo, Merck, AstraZeneca, OrigiMed, Immunomedics, and Susan G. Komen Foundation. R.J.D. is a founder of Atavistik Biosciences and an advisor for Agios Pharmaceuticals, Nirogy Therapeutics, and Vida Ventures., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Physical activity (PA) is important for managing osteoarthritis (OA), but many patients are inactive. Research is needed on strategies to leverage clinical encounters to engage patients in PA. Guided by the socioecological model of health behavior, this study aimed to engage stakeholders in the process of refining an Osteoarthritis Physical Activity Care Pathway (OA-PCP). Six focus groups and seven individual interviews were conducted with key stakeholders. Focus groups were specific to stakeholder roles and included patients with OA, support partners, and clinic personnel ( n = 6 focus groups). Interview participants were local and national PA program representatives ( n = 7 interviews). Data were analyzed by thematic analysis. Themes identified in the data included ways the OA-PCP can help patients with OA address challenges to PA engagement, strategies for connecting patients with PA resources, methods for implementing OA-PCP into clinical settings and potential use of PA trackers in the OA-PCP program. Stakeholders' comments were summarized into key recommendations for OA-PCP. Some recommendations reinforced and led to refinements in planned aspects of OA-PCP, including tailoring to individual patients, involvement of a support partner, and addressing pain with PA. Other recommendations resulted in larger changes for OA-PCP, including the addition of three email- or mail-based contacts and not requiring use of a PA tracker. The refined OA-PCP program is being evaluated in an exploratory trial, with the ultimate goal of establishing a PA program for OA that can be successfully implemented in clinical settings.