A multi-cancer early detection blood test using machine learning detects early-stage cancers lacking USPSTF-recommended screening.

US Preventive Services Task Force (USPSTF) guidelines recommend single-cancer screening for select cancers (e.g., breast, cervical, colorectal, lung). Advances in genome sequencing and machine learning have facilitated the development of blood-based multi-cancer early detection (MCED) tests intended to complement single-cancer screening. MCED tests can interrogate circulating cell-free DNA to detect a shared cancer signal across multiple tumor types. We report real-world experience with an MCED test that detected cancer signals in three individuals subsequently diagnosed with cancers of the ovary, kidney, and head/neck that lack USPSTF-recommended screening. These cases illustrate the potential of MCED tests to detect early-stage cancers amenable to cure.

Comparable low revision rates of stemmed and stemless total anatomic shoulder arthroplasties after exclusion of metal backed glenoid components: a collaboration between the Australian and Danish national shoulder arthroplasty registries.

BACKGROUND: The stemmed anatomical total shoulder arthroplasty is the gold standard in the treatment of glenohumeral osteoarthritis. However, the use of stemless total shoulder arthroplasties has increased in recent years. The number of revision procedures are relatively low and therefore it has been recommended that national joint replacement registries should collaborate when comparing revision rates. Therefore, we aimed to compare the revision rates of stemmed and stemless TSA used for the diagnosis of glenohumeral osteoarthritis using data from both the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) and the Danish Shoulder Arthroplasty Registry (DSR). METHODS: We included all patients who were registered in the AOANJRR and the DSR from January 1 2012 to December 2021 with an anatomical total shoulder arthroplasty used for osteoarthritis. Revision for any reason was used as the primary outcome. We used the Kaplan-Meier method to illustrate the cumulative revision rates and a multivariate cox regression model to calculate the hazard ratios. All analyses were performed separately for data from AOANJRR and DSR, and the results were then reported using a qualitative approach. RESULTS: 13066 arthroplasties from AOANJRR and 2882 arthroplasties from DSR were included. The hazard ratio for revision of stemmed TSA with stemless TSA as reference, adjusted for age and gender, was 1.67 (95% CI 1.34-2.09, p<0.001) in AOANJRR and 0.57 (95% CI 0.36-0.89, p=0.014) in DSR. When including glenoid type and fixation, surface bearing (only in AOANJRR) and hospital volume in the cox regression model the hazard ratio for revision of stemmed TSA compared to stemless TSA was 1.22 (95% CI 0.85-1.75, p=0.286) in AOANJRR and 1.50 (95% CI 0.91-2.45, p=0.109) in DSR. The adjusted hazard ratio for revision of total shoulder arthroplasties with metal backed glenoid components compared to all-polyethylene glenoid components was 2.54 (95% CI 1.70-3.79, p < 0.001) in AOANJRR and 4.1 (95% CI 1.92-8.58, p<0.001) in DSR. CONCLUSION: Based on data from two national shoulder arthroplasty registries, we found no significant difference in risk of revision between stemmed and stemless total shoulder arthroplasties after adjusting for the type of glenoid component. We advocate that metal-backed glenoid components should be used with caution and not on a routine basis.

A diverse portfolio of marine protected areas can better advance global conservation and equity.

Marine protected areas (MPAs) are widely used for ocean conservation, yet the relative impacts of various types of MPAs are poorly understood. We estimated impacts on fish biomass from no-take and multiple-use (fished) MPAs, employing a rigorous matched counterfactual design with a global dataset of >14,000 surveys in and around 216 MPAs. Both no-take and multiple-use MPAs generated positive conservation outcomes relative to no protection (58.2% and 12.6% fish biomass increases, respectively), with smaller estimated differences between the two MPA types when controlling for additional confounding factors (8.3% increase). Relative performance depended on context and management: no-take MPAs performed better in areas of high human pressure but similar to multiple-use in remote locations. Multiple-use MPA performance was low in high-pressure areas but improved significantly with better management, producing similar outcomes to no-take MPAs when adequately staffed and appropriate use regulations were applied. For priority conservation areas where no-take restrictions are not possible or ethical, our findings show that a portfolio of well-designed and well-managed multiple-use MPAs represents a viable and potentially equitable pathway to advance local and global conservation.

A comparison of revision rates for stemmed and stemless primary anatomic shoulder arthroplasty with all-polyethylene glenoid components: analysis from the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: We compared the rate of all-cause revision of 2 classes of primary anatomic shoulder arthroplasty, stemmed (stTSA) and stemless (slTSA), undertaken with cemented all-polyethylene glenoid components. METHODS: A large national arthroplasty registry identified 2 cohort groups for comparison, stTSA and l undertaken for all diagnoses between January 1, 2011, and December 31, 2021. A subanalysis from January 1, 2017, allowed capturing of additional patient demographics including American Society of Anesthesiologists score, body mass index, and glenoid morphology. The cumulative percent revision (CPR) was determined using Kaplan-Meier estimates of survivorship and hazard ratios (HR) from Cox proportional hazard models adjusted for age and gender. RESULTS: Of the 7995 stTSA procedures, the CPR at 9 years was 5.6% (95% confidence interval [CI]: 5.0, 6.4), and for 3156 slTSA procedures, the CPR was 4.4% (95% CI: 3.6, 5.5). There was no significant difference in the rate of revision between the study groups (HR = 0.76 [95% CI: 0.51, 1.14], P = .189, adjusted for age, gender, humeral head size, humeral fixation, bearing surface, glenoid design, and mean surgeon volume [MSV]). There was an increased rate of revision for stTSA and slTSA undertaken with humeral head sizes <44 mm (stTSA <44 mm vs. 44-50 mm, HR = 1.56 [CI: 1.18, 2.08], P = .001; slTSA <44 mm vs. 44-50 mm, HR = 2.08 [CI: 1.32, 3.33], P = .001). MSV as a continuous predictor was not a revision risk to stTSA vs. slTSA, but categorically, a low MSV (<10 stTSA + slTSA cases per annum) was associated with a higher revision rate for stTSA (10-20 cases/yr vs. <10 cases/yr, HR = 0.72 [CI: 0.55, 0.95], P = .019) but was not in slTSA. Revision rates were increased for stTSA with non-crosslinked polyethylene (XLPE) glenoids vs. XPLE after 2 years (HR = 2.20 [CI: 1.57, 3.08], P < .001) but did not significantly differ for slTSA. Metal/XPLE (humeral/glenoid) bearing surface of stTSA rate of revision was not different from each combination of slTSA bearing surface. Instability/dislocation was a revision risk for slTSA vs. stTSA (HR = 1.93 [CI: 1.28, 2.91], P = .001), but from 2017, neither of American Society of Anesthesiologists score, body mass index, and glenoid morphology changed the rate of revision. CONCLUSIONS: Revision rates of stTSA and slTSA did not significantly differ and were associated with humeral head size but not patient characteristics. Surgeon inexperience of anatomic shoulder arthroplasty and non-XLPE glenoids were risk factors for stTSA revision but not slTSA. The metal/XLPE stTSA rate of revision was not found to differ significantly from slTSA regardless of polyethylene or humeral head bearing type. Revision for instability/dislocation was more common for slTSA.

Introducing Elinor for monitoring the governance and management of area-based conservation.

Monitoring the governance and management effectiveness of area-based conservation has long been recognized as an important foundation for achieving national and global biodiversity goals and enabling adaptive management. However, there are still many barriers that prevent conservation actors, including those affected by governance and management systems from implementing conservation activities and programs and from gathering and using data on governance and management to inform decision-making across spatial scales and through time. We explored current and past efforts to assess governance and management effectiveness and barriers actors face in using the resulting data and insights to inform conservation decision-making. To help overcome these barriers, we developed Elinor, a free and open-source monitoring tool that builds on the work of Nobel Prize winner Elinor Ostrom to facilitate the gathering, storing, sharing, analyzing, and use of data on environmental governance and management across spatial scales and for areas under different governance and management types. We consider the process of codesigning and piloting Elinor with conservation scientists and practitioners and the main components of the assessment and online data system. We also consider how Elinor complements existing approaches by addressing governance and management in a single assessment at a high level for different types of area-based conservation, providing flexible options for data collection, and integrating a data system with an assessment that can support data use and sharing across different spatial scales, including global monitoring of the Global Biodiversity Framework. Although challenges will continue, the process of developing Elinor and the tool itself offer tangible solutions to barriers that prevent the systematic collection and use of governance and management data. With broader uptake, Elinor can play a valuable role in enabling more effective, inclusive, and durable area-based conservation.

Introducción de Elinor para el monitoreo de la gobernanza y la gestión de la conservación con base en zonas geográficas Resumen El monitoreo de la efectividad de la gobernanza y de la gestión de la conservación basada en zonas geográficas ha sido reconocido durante mucho tiempo como una base importante para alcanzar las metas nacionales y mundiales de la biodiversidad y permitir un manejo adaptativo. Sin embargo, todavía existen barreras que evitan que los actores de la conservación, incluidos aquellos afectados por los sistemas de gobernanza y gestión, implementen actividades y programas de conservación y recopilen y usen datos de la gobernanza y la gestión para informar las decisiones a lo largo de las escalas espaciales y a través del tiempo. Exploramos los esfuerzos hechos en la actualidad y en el pasado para evaluar la efectividad de la gobernanza y la gestión así como las barreras que los actores enfrentan al usar los datos y el conocimiento resultantes para informar la toma de decisiones de conservación. Para ayudar a derribar estas barreras desarrollamos Elinor, una herramienta de monitoreo gratuita y de software libre que parte del trabajo de la ganadora del Premio Nobel Elinor Ostrom, para facilitar la recopilación, almacenamiento, divulgación, análisis y uso de los datos sobre la gobernanza y la gestión ambiental en las escalas espaciales y para las zonas con diferentes tipos de gobernanza y gestión. Planteamos co­diseñar y pilotear Elinor con los científicos y practicantes de la conservación y usando los componentes principales del sistema de evaluación y de datos en línea. También planteamos cómo Elinor complementa las estrategias existentes al abordar la gobernanza y la gestión en una sola evaluación a un nivel elevado para diferentes tipos de conservación basada en zonas geográficas, lo que proporciona opciones flexibles para la colecta de datos, e integramos un sistema de datos con una evaluación que soporta el uso y divulgación de datos en diferentes escalas espaciales, incluido el Marco Mundial para la Biodiversidad. Aunque los retos seguirán existiendo, el proceso de desarrollo de Elinor y la propia herramienta ofrecen soluciones tangibles a las barreras que previenen la colecta sistemática y el uso de datos de la gobernanza y la gestión. Con una mayor aceptación, Elinor puede tener un papel importante en el momento de hacer posible una conservación basada en zonas geográficas más eficaz, integradora y duradera.

Primary inlay reverse shoulder arthroplasty has a higher rate of revision than onlay reverse shoulder arthroplasty: Analysis from the Australian Orthopaedic Association National Joint Replacement Registry.

Background: Two classes of primary reverse total shoulder arthroplasty (rTSA), inlay (in-rTSA), and onlay (on-rTSA) were compared to determine differences in rates of revision. Methods: Between 1 January 2012 and 31 December 2020, all primary in-rTSA or on-rTSA procedures were compared from a large national arthroplasty registry by cumulative percentage revision (CPR). Kaplan-Meier estimates of survivorship and hazard ratios from Cox proportional hazard models adjusted for age, gender, glenosphere size, and humeral fixation determined any associations to the risk of revision. Results: Of the 14,807 in-rTSA and 6590 on-rTSA procedures, the CPR at seven years was 4.9%. There was an increased risk of revision for in-rTSA vs on-rTSA (p = 0.039) when adjusted for age, gender, glenosphere size, and humeral fixation. Glenosphere size <38 mm adjusted for age and gender (p = 0.016) increased the revision risk. Revision for instability/dislocation occurred more often for in-rTSA vs on-rTSA (p < 0.001) in the first three months. Males had a higher rate of revision than females for in-rTSA (3months+, p = 0.001) and for on-rTSA (p < 0.001). Discussion: Care should be taken when considering in-rTSA particularly in males, and if preoperative planning suggests a small (<38 mm) glenosphere. Level of evidence: Level III, therapeutic study. Original article.

Chronic shoulder pain.

BACKGROUND: Chronic shoulder pain is a common presenting compliant in general practice. The differential diagnosis is broad and varies with patient age. OBJECTIVE: This article reviews the management of patients presenting with chronic shoulder pain. A structured approach to history and physical examination is presented, and appropriate investigations are discussed. Non-surgical and surgical treatment options are reviewed. DISCUSSION: Many patients presenting with chronic shoulder pain can be successfully treated non-surgically. A multidisciplinary approach including physiotherapy, occupational therapy and psychology as needed will optimise care. Patients presenting with acute injuries or 'red flag' diagnoses should be urgently referred for specialist care. Referral to an orthopaedic surgeon is also recommended for patients who have failed an appropriate course of non-surgical treatment.

Effects of management objectives and rules on marine conservation outcomes.

Understanding the relative effectiveness and enabling conditions of different area-based management tools is essential for supporting efforts that achieve positive biodiversity outcomes as area-based conservation coverage increases to meet newly set international targets. We used data from a coastal social-ecological monitoring program in 6 Indo-Pacific countries to analyze whether social, ecological, and economic objectives and specific management rules (temporal closures, fishing gear-specific, species-specific restrictions) were associated with coral reef fish biomass above sustainable yield levels across different types of area-based management tools (i.e., comparing those designated as marine protected areas [MPAs] with other types of area-based management). All categories of objectives, multiple combinations of rules, and all types of area-based management had some sites that were able to sustain high levels of reef fish biomass-a key measure for coral reef functioning-compared with reference sites with no area-based management. Yet, the same management types also had sites with low biomass. As governments advance their commitments to the Kunming-Montreal Global Biodiversity Framework and the target to conserve 30% of the planet's land and oceans by 2030, we found that although different types of management can be effective, most of the managed areas in our study regions did not meet criteria for effectiveness. These findings underscore the importance of strong management and governance of managed areas and the need to measure the ecological impact of area-based management rather than counting areas because of their designation.

Efectos de las reglas y objetivos de manejo sobre los resultados de conservación marina Resumen Es esencial entender la efectividad relativa y las condiciones habilitantes de las diferentes herramientas de manejo basadas en el área para respaldar los esfuerzos que brindan resultados positivos para la biodiversidad conforme aumenta la cobertura de la conservación basada en el área para alcanzar los objetivos internacionales recién establecidos. Usamos los datos de un programa de monitoreo socioeconómico costero en seis países del Indo-Pacífico para analizar si los objetivos sociales, ecológicos y económicos y las reglas específicas de manejo (cierres temporales, restricciones de equipo de pesca, vedas de especies) se asociaban con la biomasa de los peces de arrecife de coral por encima de los niveles de producción sustentable en diferentes tipos de herramientas de manejo basadas en el área (es decir, comparar aquellas designadas como áreas marinas protegidas[AMP] con otros tipos de manejo basado en el área). Todas las categorías de objetivos, las múltiples combinaciones de reglas y todos los tipos de manejo basado en el área tuvieron algunos sitios capaces de mantener los niveles altos de biomasa de peces de arrecife-una medida importante para el funcionamiento de los arrecifes-en comparación con los sitios de referencia sin manejo basado en el área. Sin embargo, los mismos tipos de manejo también tuvieron sitios con baja biomasa. Conforme los gobiernos avanzan en sus compromisos con el Marco Global de Biodiversidad de Kunming-Montreal y hacia el objetivo de conservar el 30% del suelo y los océanos del planeta para el 2030, descubrimos que, aunque diferentes tipos de manejo pueden ser efectivos, la mayoría de las áreas manejadas en nuestras regiones de estudio no cumplieron con los criterios de efectividad. Este descubrimiento enfatiza la importancia de una gestión y un gobierno sólidos de las áreas manejadas y la necesidad de medir el impacto ecológico del manejo basado en el área en lugar de contar las áreas por su designación.

Multi-Institutional Analysis of Cancer Patient Exposure, Perceptions, and Trust in Information Sources Regarding Complementary and Alternative Medicine.

PURPOSE: Complementary and alternative medicine (CAM) use during cancer treatment is controversial. We aim to evaluate contemporary CAM use, patient perceptions and attitudes, and trust in various sources of information regarding CAM. METHODS: A multi-institutional questionnaire was distributed to patients receiving cancer treatment. Collected information included respondents' clinical and demographic characteristics, rates of CAM exposure/use, information sources regarding CAM, and trust in each information source. Comparisons between CAM users and nonusers were performed with chi-squared tests and one-way analysis of variance. Multivariable logistic regression models for trust in physician and nonphysician sources of information regarding CAM were evaluated. RESULTS: Among 749 respondents, the most common goals of CAM use were management of symptoms (42.2%) and treatment of cancer (30.4%). Most CAM users learned of CAM from nonphysician sources. Of CAM users, 27% reported not discussing CAM with their treating oncologists. Overall trust in physicians was high in both CAM users and nonusers. The only predictor of trust in physician sources of information was income >$100,000 in US dollars per year. Likelihood of trust in nonphysician sources of information was higher in females and lower in those with graduate degrees. CONCLUSION: A large proportion of patients with cancer are using CAM, some with the goal of treating their cancer. Although patients are primarily exposed to CAM through nonphysician sources of information, trust in physicians remains high. More research is needed to improve patient-clinician communication regarding CAM use.

Predictors of Cognitive Change in Parkinson Disease: A 2-year Follow-up Study.

BACKGROUND: Mild cognitive impairment is common in Parkinson disease (PD-MCI). However, instability in this clinical diagnosis and variability in rates of progression to dementia raises questions regarding its utility for longitudinal tracking and prediction of cognitive change in PD. We examined baseline neuropsychological test and cognitive diagnosis predictors of cognitive change in PD. METHODS: Persons with PD, without dementia PD (N=138) underwent comprehensive neuropsychological assessment at baseline and were followed up to 2 years. Level II Movement Disorder Society criteria for PD-MCI and PD dementia (PDD) were applied annually. Composite global and domain cognitive z -scores were calculated based on a 10-test neuropsychological battery. RESULTS: Baseline diagnosis of PD-MCI was not associated with a change in global cognitive z -scores. Lower baseline attention and higher executive domain z -scores were associated with greater global cognitive z -score worsening regardless of cognitive diagnosis. Worse baseline domain z -scores in the attention and language domains were associated with progression to MCI or PDD, whereas higher baseline scores in all cognitive domains except executive function were associated with clinical and psychometric reversion to "normal" cognition. CONCLUSIONS: Lower scores on cognitive tests of attention were predictive of worse global cognition over 2 years of follow-up in PD, and lower baseline attention and language scores were associated with progression to MCI or PDD. However, PD-MCI diagnosis per se was not predictive of cognitive decline over 2 years. The association between higher executive domain z -scores and greater global cognitive worsening is probably a spurious result.

Lessons learned through crisis: the effect of Covid-19 on pre-service Technology Education teacher development.

The Covid-19 pandemic forced post-secondary institutions to shift their technical offerings to blended and/or remote delivery. The Pandemic was a catalyst for pre-service Technology Education programs, traditionally designed for face-to-face learning, to explore innovative pedagogical arrangements. The purpose of this study was to understand the experiences and perceptions of pre-service teachers as they navigated their way through their Pandemic-impacted Technology Education Diploma program. In particular, pre-service teachers were asked about the challenges, benefits, and lessons learned through their lived experiences dealing with the re-organization for remote and blended learning in response to the various waves of the Covid-19 Pandemic. An exploration of the learner experience within pre-service Technology Education programs contributes to a growing body of literature that continues to offer meaningful insight on the institutional arrangements to cope with the limitations brought on by the Pandemic. Interviews from a purposeful sample of nine (N = 9) pre-service teachers was the primary data source within this qualitative study that sought to understand the following research question: How have institutional responses to Covid-19 impacted the experiences and perceptions of pre-service teachers enrolled in a re-organized Technology Education Diploma program? Thematic analysis was used to identify and explore recurring nodes within the data. The findings of this study suggest that the shift in instructional modality had significant impacts on how pre-service teachers experienced their Technology Education program. The reorganization delayed the development of peer relationships within the program cohorts and disrupted lines of communication.

COVID-19-Related Employment Disruptions and Increased Financial Burden Among Survivors of Adolescent and Young Adult Cancer.

Background: Financial burden is a major concern for survivors of adolescent and young adult (AYA) cancers. We identified if employment disruptions during the COVID-19 pandemic affected AYA survivors' financial burden. Methods: AYAs who were enrolled in a cancer patient navigation program were e-mailed a survey in fall 2020. Survey items included sociodemographics, employment disruption, and two measures of financial burden: COmprehensive Score for Financial Toxicity (COST) and material and behavioral financial hardship items (for any reason, COVID-19 induced, cancer induced). Financial burden outcomes were dichotomized at the median (COST = 21; financial hardship = 3). The association of employment disruptions and sociodemographics with financial burden was assessed using multivariable logistic regression models. Results: Reduced hours/job loss was reported by 24.0% of 341 participants. Survivors with a high school education or less (odds ratio [OR]: 2.70; 95% confidence interval [CI]: 1.21-6.03) or who had decreased hours or job loss (OR: 3.97; 95% CI: 2.01-7.84) had greater odds for high financial toxicity. Reduced hours/job loss was the only factor associated with high material and behavioral financial hardship for both any reason (OR: 2.75; 95% CI: 1.41-5.33) and owing to COVID-19 (OR: 4.98; 95% CI: 2.28-10.92). Cancer treatment since March 2020 was associated with cancer-induced high material and behavioral financial hardship (OR: 3.31; 95% CI: 1.96-5.58). Conclusion: Employment disruptions owing to the COVID-19 pandemic, lower education levels, and cancer treatment were associated with high financial burden among AYA cancer survivors. Our findings suggest the need for multilevel interventions to identify and address financial burden among vulnerable cancer survivors.

Financial burdens during the COVID-19 pandemic are related to disrupted healthcare utilization among survivors of adolescent and young adult cancers.

PURPOSE: We examined whether financial burdens occurring during the COVID-19 pandemic impacted healthcare utilization among survivors of adolescent and young adult cancers. METHODS: We surveyed survivors enrolled in a patient navigation program to obtain self-reports of delayed/skipped cancer care or other care, changes to medication obtainment, and changes to medication use since the COVID-19 pandemic began. Reported financial burdens were defined as financial toxicity in the past 4 weeks (COmprehensive Score for financial Toxicity [COST] ≤ median 21) and material hardships (range = 4-11) since March 2020. Adjusted logistic regression models calculated associations and effect modification by gender. RESULTS: Survivors (n = 341) were mostly female (61.3%) and non-Hispanic White (83.3%). Nearly 20% delayed/skipped cancer care, 35.2% delayed/skipped other care, 19.1% changed medication obtainment, and 12.6% changed medication use. Greater material hardships were associated with delayed/skipped cancer care (odds ratio (OR) = 3.13, 95% CI = 1.44-6.81) and other care (OR = 2.17, 95% CI = 1.18-3.98), and changed medication obtainment (OR = 2.72, 95% CI = 1.43-5.18) or use (OR = 4.49, 95% CI = 2.05-9.80). Financial toxicity was associated with delayed/skipped other care (OR = 2.53, 95% CI = 1.31-4.89) and changed medication obtainment (OR = 1.96, 95% CI = 1.01-3.83) and medication use (OR = 3.73, 95% CI = 1.59-8.73). The association of material hardships and any changes in healthcare utilization was greater among female compared to male survivors. CONCLUSION: Financial burdens experienced during the pandemic impeded survivors' ability to utilize necessary healthcare, with worse impacts among female survivors. IMPLICATIONS FOR CANCER SURVIVORS: Delayed or skipped healthcare may lead to an increased cancer mortality or severity of therapy-related conditions. Providing resources that enable survivors experiencing financial burdens to continue critical cancer and preventive care during the COVID-19 pandemic is a priority.

Evidence of an additional centre of apple domestication in Iran, with contributions from the Caucasian crab apple Malus orientalis Uglitzk. to the cultivated apple gene pool.

Divergence processes in crop-wild fruit tree complexes in pivotal regions for plant domestication such as the Caucasus and Iran remain little studied. We investigated anthropogenic and natural divergence processes in apples in these regions using 26 microsatellite markers amplified in 550 wild and cultivated samples. We found two genetically distinct cultivated populations in Iran that are differentiated from Malus domestica, the standard cultivated apple worldwide. Coalescent-based inferences showed that these two cultivated populations originated from specific domestication events of Malus orientalis in Iran. We found evidence of substantial wild-crop and crop-crop gene flow in the Caucasus and Iran, as has been described in apple in Europe. In addition, we identified seven genetically differentiated populations of wild apple (M. orientalis), not introgressed by the cultivated apple. Niche modelling combined with genetic diversity estimates indicated that these wild populations likely resulted from range changes during past glaciations. This study identifies Iran as a key region in the domestication of apple and M. orientalis as an additional contributor to the cultivated apple gene pool. Domestication of the apple tree therefore involved multiple origins of domestication in different geographic locations and substantial crop-wild hybridization, as found in other fruit trees. This study also highlights the impact of climate change on the natural divergence of a wild fruit tree and provides a starting point for apple conservation and breeding programmes in the Caucasus and Iran.

Concordance of MRI-Guided Fusion and Systematic 12-Core Prostate Biopsy for the Detection of Prostate Cancer.

Background: MRI-guided fusion biopsy is increasingly utilized over systematic 12-core biopsy for men with MRI-visible prostate lesions. Patients and Methods: Patients with MRI visible lesions who underwent MRI-guided fusion and systematic 12-core biopsy from 2016-2020 in the Intermountain Healthcare (IHC) system were consecutively analyzed. This was in the setting of a continuous quality assurance initiative among the reading radiologists. Primary outcome was prostate cancer (PCa) detection defined by Gleason grade group (GGG) 1 or higher. Clinically significant cancer (CSC) was defined as GGG 2 or higher. Patients were stratified by biopsy date, 2016-2017 and 2018-2021, and lesions were stratified by PI-RADS v2 category. Results: A total of 184 patients with 324 MRI-detectable lesions underwent both biopsy modalities in the IHC system from 2016 to 2021. CSC was detected in 23.5% of MRI-guided fusion biopsies. Comparing PI-RAD v2 categories 1-3 to categories 4-5, rate of CSC was 10% and 42% respectively. MRI-guided fusion and systematic 12-core biopsies were concordant for PCa in 77% of men and CSC in 83%. MRI-guided fusion biopsy detected PCa in 26/103 and CSC in 20/131 men in whom systematic 12-core biopsy was negative. Systematic 12-core biopsy detected PCa in 17/94 and CSC in 11/122 men in whom MRI-guided fusion was negative. Conclusions: Omitting MRI-guided fusion or systematic 12-core biopsy would have resulted in underdiagnosis of CSC in 11% or 6% of patients respectively. Combining biopsies increased detection rate of CSC. This was in the setting of a continuous quality assurance program at a large community-based hospital.

Participation, not penalties: Community involvement and equitable governance contribute to more effective multiuse protected areas.

Accelerating ecosystem degradation has spurred proposals to vastly expand the extent of protected areas (PAs), potentially affecting the livelihoods and well-being of indigenous peoples and local communities (IPLCs) worldwide. The benefits of multiuse PAs that elevate the role of IPLCs in management have long been recognized. However, quantitative examinations of how resource governance and the distribution of management rights affect conservation outcomes are vital for long-term sustainability. Here, we use a long-term, quasi-experimental monitoring dataset from four Indonesian marine PAs that demonstrates that multiuse PAs can increase fish biomass, but incorporating multiple governance principles into management regimes and enforcing rules equitably are critical to achieve ecological benefits. Furthermore, we show that PAs predicated primarily on enforcing penalties can be less effective than those where IPLCs have the capacity to engage in management. Our results suggest that well-governed multiuse PAs can achieve conservation objectives without undermining the rights of IPLCs.

Src activates retrograde membrane traffic through phosphorylation of GBF1.

The Src tyrosine kinase controls cancer-critical protein glycosylation through Golgi to ER relocation of GALNTs enzymes. How Src induces this trafficking event is unknown. Golgi to ER transport depends on the GTP exchange factor (GEF) GBF1 and small GTPase Arf1. Here, we show that Src induces the formation of tubular transport carriers containing GALNTs. The kinase phosphorylates GBF1 on 10 tyrosine residues; two of them, Y876 and Y898, are located near the C-terminus of the Sec7 GEF domain. Their phosphorylation promotes GBF1 binding to the GTPase; molecular modeling suggests partial melting of the Sec7 domain and intramolecular rearrangement. GBF1 mutants defective for these rearrangements prevent binding, carrier formation, and GALNTs relocation, while phosphomimetic GBF1 mutants induce tubules. In sum, Src promotes GALNTs relocation by promoting GBF1 binding to Arf1. Based on residue conservation, similar regulation of GEF-Arf complexes by tyrosine phosphorylation could be a conserved and widespread mechanism.

Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19.

Importance: Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2). Objective: To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer. Design, Setting, and Participants: This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease. Exposures: Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19. Main Outcomes and Measures: The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching. Results: After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42). Conclusions and Relevance: Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity.