Needs for a conceptual bridge between biological domestication and early food globalization.

The past 15 y has seen much development in documentation of domestication of plants and animals as gradual traditions spanning millennia. There has also been considerable momentum in understanding the dispersals of major domesticated taxa across continents spanning thousands of miles. The two processes are often considered within different theoretical strains. What is missing from our repertoire of explanations is a conceptual bridge between the protracted process over millennia and the multiregional, globally dispersed nature of domestication. The evidence reviewed in this paper bears upon how we conceptualize domestication as an episode or a process. By bringing together the topics of crop domestication and crop movement, those complex, protracted, and continuous outcomes come more clearly into view.

Characterizing the etiology of recurrent tuberculosis using whole genome sequencing-Alaska, USA, 2008-2020.

BACKGROUND: Understanding the etiology of recurrent tuberculosis (rTB) is important for effective TB control. Prior to the advent of whole genome sequencing (WGS), attributing rTB to relapse or reinfection using genetic information was complicated by the limited resolution of conventional genotyping methods. METHODS: We applied a systematic method of evaluating whole genome single nucleotide polymorphism (wgSNP) distances and results of phylogenetic analyses to characterize the etiology of rTB in American Indian and Alaska Native (AIAN) persons in Alaska during 2008-2020. We contextualized our findings through descriptive analyses of surveillance data and results of a literature search for investigations that characterized rTB etiology using WGS. RESULTS: The percentage of TB cases in AIAN persons in Alaska classified as recurrent episodes (11.8%) was three times the national percentage (3.9%). Of 38 recurrent episodes included in genetic analyses, we attributed 25 (65.8%) to reinfection based on wgSNP distances and phylogenetic analyses; this proportion was the highest among 16 published point estimates identified through the literature search. By comparison, we attributed 11 of 38 (28.9%) and 6 of 38 (15.8%) recurrent episodes to reinfection based on wgSNP distances alone and on conventional genotyping methods, respectively. CONCLUSIONS: WGS and attribution criteria involving genetic distances and patterns of relatedness can provide an effective means of elucidating rTB etiology. Our findings indicate that rTB occurs at high proportions among AIAN persons in Alaska and is frequently attributable to reinfection, reinforcing the importance of active surveillance and control measures to limit the spread of TB disease in Alaskan AIAN communities.

Biochemical analysis of SARS-CoV-2 Nsp13 helicase implicated in COVID-19 and factors that regulate its catalytic functions.

Replication of the 30-kilobase genome of SARS-CoV-2, responsible for COVID-19, is a key step in the coronavirus life cycle that requires a set of virally encoded nonstructural proteins such as the highly conserved Nsp13 helicase. However, the features that contribute to catalytic properties of Nsp13 are not well established. Here, we biochemically characterized the purified recombinant SARS-CoV-2 Nsp13 helicase protein, focusing on its catalytic functions, nucleic acid substrate specificity, nucleotide/metal cofactor requirements, and displacement of proteins from RNA molecules proposed to be important for its proofreading role during coronavirus replication. We determined that Nsp13 preferentially interacts with single-stranded DNA compared with single-stranded RNA to unwind a partial duplex helicase substrate. We present evidence for functional cooperativity as a function of Nsp13 concentration, which suggests that oligomerization is important for optimal activity. In addition, under single-turnover conditions, Nsp13 unwound partial duplex RNA substrates of increasing double-stranded regions (16-30 base pairs) with similar efficiency, suggesting the enzyme unwinds processively in this range. We also show Nsp13-catalyzed RNA unwinding is abolished by a site-specific neutralizing linkage in the sugar-phosphate backbone, demonstrating continuity in the helicase-translocating strand is essential for unwinding the partial duplex substrate. Taken together, we demonstrate for the first time that coronavirus helicase Nsp13 disrupts a high-affinity RNA-protein interaction in a unidirectional and ATP-dependent manner. Furthermore, sensitivity of Nsp13 catalytic functions to Mg2+ concentration suggests a regulatory mechanism for ATP hydrolysis, duplex unwinding, and RNA protein remodeling, processes implicated in SARS-CoV-2 replication and proofreading.

Early morning sport scheduling is associated with poorer subjective sleep characteristics in British student-athletes.

This study presents the sleep characteristics of British student-athletes and examines the relationships between sport scheduling and time demands on sleep outcomes. Student-athletes (n = 157, 51% male) completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and the Sleep Hygiene Index (SHI). Self-reported sleep characteristics on weekdays and weekends, weekly frequencies of early morning and late evening sport sessions, and academic-related and sport-related time demands were also collected. Questionnaires revealed a high prevalence of undesired sleep characteristics including poor sleep quality (global PSQI >5 in 49.0%) and low sleep durations on weekdays (25% reporting <7 h). Paired t-tests revealed significant differences in bedtime, waketime, sleep duration, and sleep onset latency between weekdays and weekends (all p < 0.01). Hierarchical regression analyses indicated that early morning sport frequency was a significant predictor of PSQI (ß = 0.30) and SHI (ß = 0.24) global scores, weekday waketimes (ß = -0.17), and weekday sleep durations (ß = -0.25; all p < 0.05) in models adjusted for participant characteristics. Late evening sport frequency, and academic-related and sport-related time demands, were not significant predictors of any sleep outcome. Adjusting sport scheduling to avoid early start times could provide a means to improve sleep outcomes and may improve sporting performance and academic attainment.

Behavioral interventions and behavior change techniques used to improve sleep outcomes in athlete populations: A scoping review.

BACKGROUND: Athletes display a high prevalence of undesired sleep characteristics that may affect both performance and wellbeing. OBJECTIVES: This scoping review aimed to identify and map the existing evidence of behavioral sleep interventions and their effects on sleep outcomes in athletes, and retrospectively code the behavior change techniques (BCTs) implemented using the Behavior Change Technique Taxonomy (BCTTv1). METHODS: Conducted following the JBI methodology for scoping reviews, four online databases were used to identify prospective interventions with at least one behavioral component in competitive athletes, and reporting a sleep outcome pre- and post-intervention. RESULTS: Thirty-three studies met the inclusion criteria, encompassing 892 participants with a median age of 23. Five intervention categories were identified (education, mind-body practices, direct, multi-component, and other), with each demonstrating mixed efficacy but the potential to improve sleep outcomes. The BCTs varied in type and frequency between each category, with only 18 unique BCTs identified across all studies. CONCLUSIONS: The varied efficacy of previous studies at improving sleep outcomes may be attributed to the lack of behavior change theory applied during intervention development. Designing interventions following a targeted specification of the behavioral problem, and the integration of corresponding BCTs should be considered in future research.

Decentralised clinical trials in rural Australia: Opportunities and challenges.

AIMS: To present opportunities and a model to redress the under-representation of rural communities and people in Australian clinical trials. CONTEXT: Clinical trials are essential for building and understanding the health evidence base. The lack of representation of rural people in clinical trials is evident in other countries. Examining the Australian New Zealand Clinical Trial Registry (ANZCTR) suggests this is also the case in Australia. APPROACH: We propose an approach that empowers rurally based academics and clinicians to co-design clinical trials and increase rural Australians' participation in clinical trials to address this inequality of access. A case study of a decentralised, co-designed clinical trial is presented to support this approach. CONCLUSION: Decentralising clinical trials could improve access to clinical trials, strengthen the social capital of rural communities and help address the health inequalities that exist between rural and metropolitan communities.

Deep learning for automatic segmentation of the nuclear envelope in electron microscopy data, trained with volunteer segmentations.

Advancements in volume electron microscopy mean it is now possible to generate thousands of serial images at nanometre resolution overnight, yet the gold standard approach for data analysis remains manual segmentation by an expert microscopist, resulting in a critical research bottleneck. Although some machine learning approaches exist in this domain, we remain far from realizing the aspiration of a highly accurate, yet generic, automated analysis approach, with a major obstacle being lack of sufficient high-quality ground-truth data. To address this, we developed a novel citizen science project, Etch a Cell, to enable volunteers to manually segment the nuclear envelope (NE) of HeLa cells imaged with serial blockface scanning electron microscopy. We present our approach for aggregating multiple volunteer annotations to generate a high-quality consensus segmentation and demonstrate that data produced exclusively by volunteers can be used to train a highly accurate machine learning algorithm for automatic segmentation of the NE, which we share here, in addition to our archived benchmark data.

Online citizen science with the Zooniverse for analysis of biological volumetric data.

Public participation in research, also known as citizen science, is being increasingly adopted for the analysis of biological volumetric data. Researchers working in this domain are applying online citizen science as a scalable distributed data analysis approach, with recent research demonstrating that non-experts can productively contribute to tasks such as the segmentation of organelles in volume electron microscopy data. This, alongside the growing challenge to rapidly process the large amounts of biological volumetric data now routinely produced, means there is increasing interest within the research community to apply online citizen science for the analysis of data in this context. Here, we synthesise core methodological principles and practices for applying citizen science for analysis of biological volumetric data. We collate and share the knowledge and experience of multiple research teams who have applied online citizen science for the analysis of volumetric biological data using the Zooniverse platform ( www.zooniverse.org ). We hope this provides inspiration and practical guidance regarding how contributor effort via online citizen science may be usefully applied in this domain.

Bridging imaging users to imaging analysis - A community survey.

The 'Bridging Imaging Users to Imaging Analysis' survey was conducted in 2022 by the Center for Open Bioimage Analysis (COBA), BioImaging North America (BINA) and the Royal Microscopical Society Data Analysis in Imaging Section (RMS DAIM) to understand the needs of the imaging community. Through multichoice and open-ended questions, the survey inquired about demographics, image analysis experiences, future needs and suggestions on the role of tool developers and users. Participants of the survey were from diverse roles and domains of the life and physical sciences. To our knowledge, this is the first attempt to survey cross-community to bridge knowledge gaps between physical and life sciences imaging. Survey results indicate that respondents' overarching needs are documentation, detailed tutorials on the usage of image analysis tools, user-friendly intuitive software, and better solutions for segmentation, ideally in a format tailored to their specific use cases. The tool creators suggested the users familiarise themselves with the fundamentals of image analysis, provide constant feedback and report the issues faced during image analysis while the users would like more documentation and an emphasis on tool friendliness. Regardless of the computational experience, there is a strong preference for 'written tutorials' to acquire knowledge on image analysis. We also observed that the interest in having 'office hours' to get an expert opinion on their image analysis methods has increased over the years. The results also showed less-than-expected usage of online discussion forums in the imaging community for solving image analysis problems. Surprisingly, we also observed a decreased interest among the survey respondents in deep/machine learning despite the increasing adoption of artificial intelligence in biology. In addition, the community suggests the need for a common repository for the available image analysis tools and their applications. The opinions and suggestions of the community, released here in full, will help the image analysis tool creation and education communities to design and deliver the resources accordingly.

Supporting nursing and allied health student placements in rural and remote Australia: a narrative review of publications by university departments of rural health.

University departments of rural health are Commonwealth-funded to improve recruitment and retention of the rural allied health and nursing (including midwifery) workforce, primarily through student placements. We examined publications by university departments of rural health that were focused on allied health and nursing students undertaking placements in rural Australia, to understand the characteristics, main findings and implications of the research conducted. Interprofessional learning was a key feature of placements and placement education, although other activities such as community engagement added to placement experiences. Factors such as quality supervision and being involved in the community contributed to a positive placement experience and increased rural practice intention. Tracking studies showed a relationship between rural placements, rural practice intention and rural practice. Rural placements occurred across a variety of settings and in locations consistent with the policy framework. Embedding university departments of rural health in rural communities enabled staff to build relationships and increase placement capacity.

Do undertaking rural placements and place of origin inform where allied health graduates work in South Australia?

OBJECTIVE: To examine the principal place of practice after graduation of students who participated in the Rural Health Multidisciplinary Training (RHMT) program and allied health students' place of origin. DESIGN: Cross-sectional study. PARTICIPANTS: Graduates who completed their degree in podiatry, occupational therapy and physiotherapy in 2019. MAIN OUTCOME MEASURES: Principal place of practice at first and third years after graduation. RESULTS: In 2020, 40 allied health professionals (AHPs) who graduated from the University of South Australia in 2019 were practising in rural areas but only 26 of them remained in the rural practice in 2022. The retention rate for rural practice was 65% within 2 years. However, in 2022, 25 allied health professionals left their metropolitan employment location and transitioned to rural practice. Of the 25 allied health graduates who joined the rural practice in 2022, most of them (80%, 20/25) had either rural exposure through the RMHT program or were from rural origin. CONCLUSIONS: Rural exposure via the RHMT program and allied health students' rural place of origin have an important role for rural principal place of practice at first and third years after graduation.

Co-designing a peer-led model of delivering behavioural activation for people living with depression or low mood in Australian farming communities.

INTRODUCTION: Farmers face a range of factors that negatively influence their mental health and suicide risk, yet have limited access to appropriate support. Behavioural activation (BA) is an evidence-based therapy that can be effectively delivered by nonclinical workers. Working with members of farming communities to deliver BA to their peers has the potential to overcome many well-established barriers to mental health help-seeking and improve outcomes for this at-risk group. OBJECTIVE: This paper describes the findings of a co-design phase informing the development of a peer (farmer)-led approach for delivering BA for farmers living with depression or low mood. DESIGN: This qualitative study used a co-design approach involving members of the target community. Focus groups were transcribed and analysed using Thematic Analysis and the Framework approach. FINDINGS: Ten online focus groups with 22 participants were held over 3 months. Four overarching, interlinked themes were identified: (i) filling the gap in rural mental health support; (ii) alignment with the farming context-tailoring how, where and when we engage about mental health; (iii) the 'messenger' is as important as the message; and (iv) sustainability, governance and support. DISCUSSION: Findings suggest BA could be a contextually appropriate model of support for the farming community-given its practical and solution-focused approach-and could help improve access to support. Having peer workers deliver the intervention was viewed as appropriate. Ensuring governance structures are developed to support peers to deliver the intervention will be essential to facilitate effectiveness, safety and sustainability. CONCLUSION: Insights gained through co-design have been critical to the success of developing this new model of support for members of farming communities experiencing depression or low mood.

Development of the ARENA training programme for resilient performance in defense and security settings.

Defense and Security Personnel (DSP) often have to operate in the presence of stressful demands. Prior research has identified factors and processes associated with DSP being able to perform resiliently in demanding situations and settings. The aim of the present study was to develop a resilient performance training programme for UK defense and security operators. An intervention mapping (IM) method was used to guide the development of the programme. Typically, IM follows six sequential phases. In the present work, these phases were shaped by insights from prior research (e.g. systematic review and end user interviews), the input of a dedicated working group (N = 13) and from practitioner focus groups. During the IM process, the importance of programme flexibility was emphasized by practitioners. As such, the enAbling REsilieNt performAnce (ARENA) training programme was designed to be agile and include both face-to-face training and online learning modules. Theoretical behavior change principles, closely aligned to findings of earlier work on resilient defense and security performance, were used to underpin programme content and delivery. Future research should seek to gather data on the impact of the ARENA programme, in the targeted biological, psychological and social factors that previously been associated with resilient performances.

Bayesian Self-Optimization for Telescoped Continuous Flow Synthesis.

The optimization of multistep chemical syntheses is critical for the rapid development of new pharmaceuticals. However, concatenating individually optimized reactions can lead to inefficient multistep syntheses, owing to chemical interdependencies between the steps. Herein, we develop an automated continuous flow platform for the simultaneous optimization of telescoped reactions. Our approach is applied to a Heck cyclization-deprotection reaction sequence, used in the synthesis of a precursor for 1-methyltetrahydroisoquinoline C5 functionalization. A simple method for multipoint sampling with a single online HPLC instrument was designed, enabling accurate quantification of each reaction, and an in-depth understanding of the reaction pathways. Notably, integration of Bayesian optimization techniques identified an 81 % overall yield in just 14 h, and revealed a favorable competing pathway for formation of the desired product.

CancerMine: a literature-mined resource for drivers, oncogenes and tumor suppressors in cancer.

Tumors from individuals with cancer are frequently genetically profiled for information about the driving forces behind the disease. We present the CancerMine resource, a text-mined and routinely updated database of drivers, oncogenes and tumor suppressors in different types of cancer. All data are available online ( http://bionlp.bcgsc.ca/cancermine ) and downloadable under a Creative Commons Zero license for ease of use.

Lessons learnt from MDM2 fluorescence in-situ hybridisation analysis of 439 mature lipomatous lesions with an emphasis on atypical lipomatous tumour/well-differentiated liposarcoma lacking cytological atypia.

AIMS: Amplification of the murine double minute-2 (MDM2) gene, which is usually detected with fluorescence in-situ hybridisation (FISH), is the key driving event for atypical lipomatous tumours (ALTs)/well-differentiated liposarcomas (WDLs). We sought to determine the concordance between the histopathological findings and MDM2 FISH in the diagnosis of ALT/WDL, and to identify the histological features of MDM2-amplified tumours lacking classic atypia. METHODS AND RESULTS: We performed a retrospective analysis of all mature lipomatous lesions subjected to MDM2 FISH analysis at our institution. MDM2 FISH analysis was performed on 439 mature lipomatous lesions: 364 (82.9%) were negative and 75 (17%) were positive. In 17 of 75 (22.6%) ALTs/WDLs, cytological atypia was not identified on initial histological assessment, thus favouring lipoma. On review, these cases shared common histological features, consisting of a very low number of relatively small stromal cells within the tumour lobules, with mildly coarse chromatin and oval nuclei, admixed with unremarkable adipocytes in a tumour background devoid of fibroconnective septa, areas of fibrosis, or blood vessels. These cells matched the cells in which FISH showed MDM2 amplification. In contrast, 13 cases (3.5%) regarded as suspicious for ALT/WDL on the basis of histology lacked MDM2 amplification and were reclassified following the FISH findings. CONCLUSIONS: We conclude that a subset of lipoma-like ALTs/WDLs are not associated with any of the features typically described in ALT/WDL. Our study also showed that tumours >100 mm are more likely to be ALT/WDL; however, a history of recurrence or concerning clinical/radiological features was not significantly associated with classification as ALT/WDL.

"I have the strength to get through this using my past experiences with HIV": findings from a mixed-method survey of health outcomes, service accessibility, and psychosocial wellbeing among people living with HIV during the Covid-19 pandemic.

We examined the impact of Covid-19 restrictions on the wellbeing and access to care among people living with HIV (PLWH) in the UK. A cross-sectional anonymous online survey was circulated to PLWH attending care at three HIV services in Sussex. The questionnaire covered key themes: socio-demographic characteristics; changes in physical and mental health; accessibility of essential health services and information; and socio-economic concerns. Free-text qualitative responses were examined through framework analysis. Quantitative data from 653 respondents were available, with a subset of 385 free-text qualitative responses. In terms of mental health, 501 (77.6%) respondents reported feeling more anxious; 464 (71.8%) reported feeling more depressed than usual; and 128 (19.8%) reported having suicidal thoughts since the start of the pandemic. Respondents worried about running out of HIV medicine (n = 264, 40.7%); accessing HIV services (n = 246, 38.0%) as well as other health services (n = 408, 63.0%). Widespread resilience was also noted: 537 (83.3%) of respondents felt that living with HIV had equipped them with the strength to adapt to the Covid-19 pandemic. Findings highlight important gaps between the multifaceted needs of PLWH. Multisectoral collaborations and investments are needed to adequately support PLWH and to build resilience to future shocks within HIV services.

Bilateral Transverse Upper Gracilis Flaps for Unilateral Breast Reconstruction: A 4-Year Retrospective Study of the "2-in-1" Technique and a Systematic Review With Meta-analysis.

INTRODUCTION: The transverse upper gracilis (TUG) flap is a reliable alternative to abdominally based breast reconstruction because of its advantageous anatomy. However, the limited tissue volume prevents reconstruction of large breasts. The bilateral TUG flaps for unilateral breast reconstruction can overcome this problem. METHODS: A retrospective analysis was performed regarding unilateral breast reconstruction with bilateral TUGs at the Queen Victoria Hospital from 2015 to 2019. Associations between categorical variables were examined with Fisher exact test, and any differences in continuous variables by complication status were evaluated with Mann-Whitney-Wilcoxon test for independent samples. A relevant systematic review was conducted with a meta-analysis of proportions using the Freeman-Tukey arcsine transformation for the estimation of the overall survival rates. RESULTS: Ten cases were identified with 6 having a delayed reconstruction. Median age and body mass index were 50.8 years and 23.9 kg/m 2 , respectively, and average flap weight was 268.3 g. One flap was placed superiorly with its pedicle anastomosed to the retrograde internal mammary vessels, except of half of the cases where a second anterograde vein was used. The mean follow-up was 21.4 months, and all flaps survived. Two patients returned to theater, and 4 experienced donor-site problems. The presence of complications was not associated with age, ever smoking, body mass index, TUG weight, or anastomosis to retrograde internal mammary vein. The systematic review resulted in 8 eligible articles with a total sample of 156 flaps. The overall survival rate was 96.8%. In 6 cases, the indication was Poland syndrome (7.7%), and in 48.7%, axillary vessels were also used as recipient vessels. The estimated overall flap survival rate was 100% (95% confidence interval, 99%-100%), and no significant heterogeneity was noted ( I2 = 0%, P = 0.71). CONCLUSIONS: The "2-in-1" technique can lead to symmetrical aesthetically pleasant results for both recipient and donor sites. Our case series and the conducted systematic review reiterate the reliability of this approach.

Quantification of Multi-class Cyanopeptides in Swiss Lakes with Automated Extraction, Enrichment and Analysis by Online-SPE HPLC-HRMS/MS.

The frequency and intensity of cyanobacterial blooms continue to increase in freshwater systems across the globe. Cyanobacteria can release toxins and several bioactive secondary metabolites and analytical methods are needed to effectively assess their concentrations in surface waters. Since booms can evolve rapidly in parts of a lake, high resolution of spatial and temporal sampling increases the complexity of monitoring efforts. Here, we present the validation of an automated, online-solid phase extraction (SPE) high performance liquid chromatography (HPLC)-high resolution tandem mass spectrometry (HRMS/MS) method. This online-SPE HPLC-HRMS/MS methods enables quantitative monitoring of surface waters for 17 cyanobacterial peptides (cyanopeptides), spanning 5 distinct cyanopeptide classes, including: microcystins, anabaenopeptins, nodularins, cyclamides and cyanopeptolins. The method can quantify these cyanopeptides in the low ng/L-range with high accuracy (85-116%) and low relative matrix effects (<25%). We demonstrated its application to Swiss lake waters (Zürichsee, Hallwilersee, Greifensee), which also highlighted the value of adding cyanopeptides beyond common microcystins when monitoring surface waters for cyanobacteria.

Stakeholders' perceptions of how nurse-physician communication may impact patient care: protocol for a concept mapping study.

Effective nurse-physician interprofessional communication is important to ensure that patients receive evidence-based care and treatment. There is a gap in knowledge about how nurse-physician communication impacts patient care. We propose using concept mapping to develop an in-depth understanding of patients, nurses, and physicians' perspectives on how physician-nurse communication affects patient care. There are six phases to concept mapping: determining the focus, generating statements, structuring statements, producing the map, interpretating the map, and map utilization. We will use 'Ariadne', a concept mapping software package for data collection and analysis. The study outcome will be a two-dimensional concept map providing a visual representation of how nurse-physician communication influences patient care. We will report similarity and differences among three stakeholder groups. Our research will inform the development of testable hypotheses about nurse-physician communication and patient care.