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Degenerative Cervical Myelopathy (DCM) is a common and disabling condition, with a relatively modest research capacity. In order to accelerate knowledge discovery, the AO Spine RECODE-DCM project has recently established the top priorities for DCM research. Uptake of these priorities within the research community will require their effective dissemination, which can be supported by identifying key opinion leaders (KOLs). In this paper, we aim to identify KOLs using artificial intelligence. We produce and explore a DCM co-authorship network, to characterise researchers' impact within the research field. Through a bibliometric analysis of 1674 scientific papers in the DCM field, a co-authorship network was created. For each author, statistics about their connections to the co-authorship network (and so the nature of their collaboration) were generated. Using these connectedness statistics, a neural network was used to predict H-Index for each author (as a proxy for research impact). The neural network was retrospectively validated on an unseen author set. DCM research is regionally clustered, with strong collaboration across some international borders (e.g., North America) but not others (e.g., Western Europe). In retrospective validation, the neural network achieves a correlation coefficient of 0.86 (p<0.0001) between the true and predicted H-Index of each author. Thus, author impact can be accurately predicted using only the nature of an author's collaborations. Analysis of the neural network shows that the nature of collaboration strongly impacts an author's research visibility, and therefore suitability as a KOL. This also suggests greater collaboration within the DCM field could help to improve both individual research visibility and global synergy.

Robust and cost-effective genome editing in a diverse array of cells and model organisms is now possible thanks to the discovery of the RNA-guided endonucleases of the CRISPR-Cas system. The commonly used Cas9 of Streptococcus pyogenes shows high levels of activity but, depending on the application, has been associated with some shortcomings. Firstly, the enzyme has been shown to cause mutagenesis at genomic sequences resembling the target sequence. Secondly, the stringent requirement for a specific motif adjacent to the selected target site can limit the target range of this enzyme. Lastly, the physical size of Cas9 challenges the efficient delivery of genomic engineering tools based on this enzyme as viral particles for potential therapeutic applications. Related and parallel strategies have been employed to address these issues. Taking advantage of the wealth of structural information that is becoming available for CRISPR-Cas effector proteins, Cas9 has been redesigned by mutagenizing key residues contributing to activity and target recognition. The protein has also been shortened and redesigned into component subunits in an attempt to facilitate its efficient delivery. Furthermore, the CRISPR-Cas toolbox has been expanded by exploring the properties of Cas9 orthologues and other related effector proteins from diverse bacterial species, some of which exhibit different target site specificities and reduced molecular size. It is hoped that the improvements in accuracy, target range and efficiency of delivery will facilitate the therapeutic application of these site-specific nucleases.

Introduction: Rural populations routinely rank poorly on common health indicators. While it is understood that rural residents face barriers to health care, the exact nature of these barriers remains unclear. To further define these barriers, a qualitative study of primary care physicians practicing in rural communities was performed. Methods: Semistructured interviews were conducted with primary care physicians practicing in rural areas within western Pennsylvania, the third largest rural population within the USA, using purposively sampling. Data were then transcribed, coded, and analyzed by thematic analysis. Results: Three key themes emerged from the analysis addressing barriers to rural health care: (1) cost and insurance, (2) geographic dispersion, and (3) provider shortage and burnout. Providers mentioned strategies that they either employed or thought would be beneficial for their rural communities: (1) subsidize services, (2) establish mobile and satellite clinics (particularly for specialty care), (3) increase utilization of telehealth, (4) improve infrastructure for ancillary patient support (ie social work services), and (5) increase utilization of advanced practice providers. Conclusion: There are numerous barriers to providing rural communities with quality health care. Barriers that are encountered are multidimensional. Patients are unable to obtain the care they need because of cost-related barriers. More providers need to be recruited to rural areas to combat the shortage and burnout. Advanced care-delivery methods such as telehealth, satellite clinics, or advanced practice providers can help bridge the gaps caused by geographic dispersion. Policy efforts should target all these aspects in order to appropriately address rural healthcare needs.

Individuals with lifelong illnesses need access to adequate information about their condition to make optimal health decisions. Degenerative Cervical Myelopathy (DCM) is the most common form of spinal cord dysfunction in adults worldwide. Its chronic and debilitating nature, varied impact, clinical trajectory, and management options necessitate appropriate informational support to sustain effective clinical and self-directed care strategies. However, before clinicians can meet patients' information needs, they must first have an understanding of their baseline requirements. This study explores the information needs of people with DCM (PwCM). In doing so, it provides a starting point for the development of patient education and knowledge management strategies in clinical practice. Semi-structured interviews with PwCM were conducted using an interview guide. Interviews were audio-recorded and transcribed verbatim. Thematic analysis according to Braun and Clarke's six-phase approach was used to analyse the data. Findings were reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. Twenty PwCM (65% female, 35% male), with ages ranging from 39 to 74 years old participated in the interviews. The findings indicated that the provision of information to PwCM during clinical interactions varies. Accordingly, PwCM's information needs were broad-ranging, as was the nature of the information they found useful. Three main themes were identified (1) Variation in the provision of information to PwCM during clinical interactions, (2) Variations in the information needs of PwCM, and (3) Information that PwCM find useful. Efforts must turn to adequately educating patients at the time of the clinical encounter. A comprehensive and consistent patient-centered information exchange in DCM is necessary to achieve this.

Background Degenerative cervical myelopathy (DCM) is a poorly recognised form of spinal cord injury which arises when degenerative changes in the cervical spine injure the spinal cord. Timely surgical intervention is critical to preventing disability. Despite this, DCM is frequently undiagnosed, and may be misconstrued as normal ageing. For a disease associated with age, we hypothesised that the elderly may represent an underdiagnosed population. This study aimed to evaluate this hypothesis by comparing age-stratified estimates of DCM prevalence based on spinal cord compression (SCC) data with hospital-diagnosed prevalence in the UK. Methods We queried the UK Hospital Episode Statistics database for admissions with a primary diagnosis of DCM. Age-stratified incidence rates were calculated and extrapolated to prevalence by adjusting population-level life expectancy to the standardised mortality ratio of DCM. We compared these figures to estimates of DCM prevalence based on the published conversion rate of asymptomatic SCC to DCM. Results The mean prevalence of DCM across all age groups was 0.19% (0.17, 0.21), with a peak prevalence of 0.42% at age 50–54 years. This contrasts with estimates from SCC data which suggest a mean prevalence of 2.22% (0.436, 2.68) and a peak prevalence of 4.16% at age > 79 years. Conclusions To our knowledge, this is the first study to estimate the age-stratified prevalence of DCM and estimate underdiagnosis. There is a substantial difference between estimates of DCM prevalence derived from SCC data and UK hospital activity data. This is greatest amongst elderly populations, indicating a potential health inequality.

Timing and rate of nitrogen (N) fertilizer application can influence maize (Zea mays L.) grain yield, N uptake, and nitrogen use efficiency (NUE) parameters, but results have been inconsistent across the upper Midwest. This study compared single (fall and preplant) and split applications of differing N rates for maize under irrigated conditions on loamy sand at Becker, MN and under rainfed conditions on loam and clay loam soils at Lamberton, MN and Waseca, MN, respectively, in 2014 to 2016. Fall and preplant applications of N were applied at recommended and 125% of recommended rates (RN) according to University of Minnesota guidelines. Split-application treatments included a two-way (Sp, applied at 75% and 100% of RN) and a three-way split (TSp applied at 50%, 75%, and 100% of RN), with the total N rate equally split among application times. At Becker, maize grain yield with TSp was 12.6 to 15.7 Mg ha-1 among years and significantly greater than that with fall or preplant treatments. The TSp treatment also improved agronomic efficiency (AE) and recovery efficiency (RE) by an average of 30% over fall or preplant treatments. At Lamberton, maize grain yield, AE and RE did not differ among treatments. However, TSp75 improved AE by 8.3 kg kg-1 while producing comparable yields to fall and preplant treatments. At Waseca, Sp or TSp improved grain yield and AE compared with fall treatments. These results suggest that split applications of N can increase maize grain yield, AE, and RE on irrigated coarse-textured soils and applying N fertilizer near planting or as a split application can improve N management on non-irrigated clay loam soils.

During meiotic recombination, homologue-templated repair of programmed DNA double-strand breaks (DSBs) produces relatively few crossovers and many difficult-to-detect non-crossovers. By intercrossing two diverged mouse subspecies over five generations and deep-sequencing 119 offspring, we detect thousands of crossover and non-crossover events genome-wide with unprecedented power and spatial resolution. We find that both crossovers and non-crossovers are strongly depleted at DSB hotspots where the DSB-positioning protein PRDM9 fails to bind to the unbroken homologous chromosome, revealing that PRDM9 also functions to promote homologue-templated repair. Our results show that complex non-crossovers are much rarer in mice than humans, consistent with complex events arising from accumulated non-programmed DNA damage. Unexpectedly, we also find that GC-biased gene conversion is restricted to non-crossover tracts containing only one mismatch. These results demonstrate that local genetic diversity profoundly alters meiotic repair pathway decisions via at least two distinct mechanisms, impacting genome evolution and Prdm9 -related hybrid infertility. During meiotic recombination, genetic information is transferred or exchanged between parental chromosome copies. Using a large hybrid mouse pedigree, the authors generated high-resolution maps of these transfer/exchange events and discovered new properties governing their processing and resolution.

Degenerative cervical myelopathy (DCM) is a common and disabling condition. Early effective treatment is limited by late diagnosis. Conventional descriptions of DCM focus on motor and sensory limb disability, however, recent work suggests the true impact is much broader. This study aimed to characterise the symptomatic presentation of DCM from the perspective of people with DCM and determine whether any of the reported symptoms, or groups of symptoms, were associated with early diagnosis. An internet survey was developed, using an established list of patient-reported effects. Participants (N = 171) were recruited from an online community of people with DCM. Respondents selected their current symptoms and primary presenting symptom. The relationship of symptoms and their relationship to time to diagnosis were explored. This included symptoms not commonly measured today, termed 'non-conventional' symptoms. All listed symptoms were experienced by >10% of respondents, with poor balance being the most commonly reported (84.2%). Non-conventional symptoms accounted for 39.7% of symptomatic burden. 55.4% of the symptoms were reported as an initial symptom, with neck pain the most common (13.5%). Non-conventional symptoms accounted for 11.1% of initial symptoms. 79.5% of the respondents were diagnosed late (>6 months). Heavy legs was the only initial symptom associated with early diagnosis. A comprehensive description of the self-reported effects of DCM has been established, including the prevalence of symptoms at disease presentation. The experience of DCM is broader than suggested by conventional descriptions and further exploration of non-conventional symptoms may support earlier diagnosis.

Flares produced following the tidal disruption of stars by supermassive black holes can reveal the properties of the otherwise dormant majority of black holes and the physics of accretion. In the past decade, a class of optical-ultraviolet tidal disruption flares has been discovered whose emission properties do not match theoretical predictions. This has led to extensive efforts to model the dynamics and emission mechanisms of optical-ultraviolet tidal disruptions in order to establish them as probes of supermassive black holes. Here we present the optical-ultraviolet tidal disruption event AT 2022dbl, which showed a nearly identical repetition 700 days after the first flare. Ruling out gravitational lensing and two chance unrelated disruptions, we conclude that at least the first flare represents the partial disruption of a star, possibly captured through the Hills mechanism. Since both flares are typical of the optical-ultraviolet class of tidal disruptions in terms of their radiated energy, temperature, luminosity, and spectral features, it follows that either the entire class are partial rather than full stellar disruptions, contrary to the prevalent assumption, or some members of the class are partial disruptions, having nearly the same observational characteristics as full disruptions. Whichever option is true, these findings could require revised models for the emission mechanisms of optical-ultraviolet tidal disruption flares and a reassessment of their expected rates.