A minimum data set-Core outcome set, core data elements, and core measurement set-For degenerative cervical myelopathy research (AO Spine RECODE DCM): A consensus study.

BACKGROUND: Degenerative cervical myelopathy (DCM) is a progressive chronic spinal cord injury estimated to affect 1 in 50 adults. Without standardised guidance, clinical research studies have selected outcomes at their discretion, often underrepresenting the disease and limiting comparability between studies. Utilising a standard minimum data set formed via multi-stakeholder consensus can address these issues. This combines processes to define a core outcome set (COS)-a list of key outcomes-and core data elements (CDEs), a list of key sampling characteristics required to interpret the outcomes. Further "how" these outcomes should be measured and/or reported is then defined in a core measurement set (CMS). This can include a recommendation of a standardised time point at which outcome data should be reported. This study defines a COS, CDE, and CMS for DCM research. METHODS AND FINDINGS: A minimum data set was developed using a series of modified Delphi processes. Phase 1 involved the setup of an international DCM stakeholder group. Phase 2 involved the development of a longlist of outcomes, data elements, and formation into domains. Phase 3 prioritised the outcomes and CDEs using a two-stage Delphi process. Phase 4 determined the final DCM minimal data set using a consensus meeting. Using the COS, Phase 5 finalised definitions of the measurement construct for each outcome. In Phase 6, a systematic review of the literature was performed, to scope and define the psychometric properties of measurement tools. Phase 7 used a modified Delphi process to inform the short-listing of candidate measurement tools. The final measurement set was then formed through a consensus meeting (Phase 8). To support implementation, the data set was then integrated into template clinical research forms (CRFs) for use in future clinical trials (Phase 9). In total, 28 outcomes and 6 domains (Pain, Neurological Function, Life Impact, Radiology, Economic Impact, and Adverse Events) were entered into the final COS. Thirty two outcomes and 4 domains (Individual, Disease, Investigation, and Intervention) were entered into the final CDE. Finally, 4 outcome instruments (mJOA, NDI, SF-36v2, and SAVES2) were identified for the CMS, with a recommendation for trials evaluating outcomes after surgery, to include baseline measurement and at 6 months from surgery. CONCLUSIONS: The AO Spine RECODE-DCM has produced a minimum data set for use in DCM clinical trials today. These are available at https://myelopathy.org/minimum-dataset/. While it is anticipated the CDE and COS have strong and durable relevance, it is acknowledged that new measurement tools, alongside an increasing transition to study patients not undergoing surgery, may necessitate updates and adaptation, particularly with respect to the CMS.

Degenerative Cervical Myelopathy Awareness in Primary Care: UK National Cross-Sectional Survey of General Practitioners.

BACKGROUND: Degenerative cervical myelopathy (DCM) is a progressive neurological condition, characterized by spinal cord injury secondary to degenerative changes in the spine. Misdiagnosis in primary care forms part of a complex picture leading to an average diagnostic delay of 2 years. This leads to potentially preventable and permanent disability. A lack of awareness secondary to deficits in postgraduate education may contribute to these delays. OBJECTIVE: This study aims to assess the awareness of DCM in the setting of general practice. METHODS: General practitioners completed a quantitative web-based cross-sectional questionnaire. The 17-item questionnaire captured data regarding demographics, subjective awareness, and objective knowledge. The questionnaire was disseminated via professional networks, including via practice managers and senior practice partners. Incentivization was provided via a bespoke DCM fact sheet for those that completed the survey. RESULTS: A total of 54 general practitioners representing all 4 UK nations responded to the survey. General practitioners most commonly self-assessed that they had "limited awareness" of DCM (n=24, 51%). General practitioners felt most commonly "moderately able" to recognize a case of DCM (n=21, 46%). In total, 13% (n=6) of respondents reported that they would not be at all able to recognize a patient with DCM. Respondents most commonly reported that they were "moderately confident" in their ability to triage a patient with DCM (n=19, 41%). A quarter of respondents reported no prior introduction to DCM throughout their medical training (n=13, 25%). The mean score for knowledge-based questions was 42.6% (SD 3.96%) with the lowest performance observed in patient demographic and clinical recognition items. CONCLUSIONS: General practitioners lack confidence in the recognition and management of DCM. These findings are consistent with the diagnostic delays previously described in the literature at the primary care level. Further work to develop and implement educational interventions to general practitioner practices is a crucial step to improving patient outcomes in DCM.

"Factors influencing readmission patterns following radical cystectomy: An analysis of social determinants and discharge outcomes".

INTRODUCTION AND OBJECTIVES: Radical cystectomy readmission rates remain high, with around 25% of patients readmitted to index and nonindex hospitals in 30 days. Nonindex readmissions have been associated with poorer outcomes, including longer lengths of stay and higher mortality rates. This study aimed to examine the associations of social factors (e.g., sex, race, socioeconomic status, insurance type, and resident location) on readmission to index versus nonindex hospitals and discharge disposition. METHODS: We conducted a population-based retrospective study using the Pennsylvania Cancer Registry (PCR) to identify patients diagnosed with nonmetastatic muscle-invasive bladder cancer who underwent radical cystectomy in Pennsylvania between 2010 and 2018. Readmitted patients were identified using the Pennsylvania Health Care Cost Containment Council data (PHC4). The primary outcome was readmission location (i.e., index or nonindex hospital) following radical cystectomy. We used chi-square tests for categorical variables, Wilcoxon rank sum test for continuous variables, multivariable logistic regression model to assess predictors of being readmitted to an index hospital and calculating the predicted probability of being admitted to an index hospital depending on discharge disposition. RESULTS: A total of 517 patients were readmitted within 30-days after radical cystectomy. The majority of readmissions were index readmissions (83%). Median readmission hospital stay was 4 days (interquartile range [IQR] 4) for index and 5 days (IQR 7) for nonindex hospitals, P = 0.01. Patients readmitted to index hospitals had fewer comorbidities (median weighted Elixhauser Comorbidity Index 2 (IQR 2)) and lived in urban areas (89%). Discharge with home care was associated with a higher odds of index readmission (odds ratio, [OR] 2.40; 95% confidence interval, [CI] 1.25-4.52). CONCLUSIONS: Patients residing in urban areas and with fewer comorbidities were more likely to be readmitted to index hospitals than nonindex hospitals. Socioeconomic status and insurance type did not correlate with the type of readmission. Finally, being discharged with home health care was found to be a predictor of readmission to an index hospital.

Effect of Private Equity Ownership on Access to Outpatient Urologic Cancer Care in Medicare Recipients.

OBJECTIVES: To compare appointment availability and wait times between private equity--owned and non-private equity-owned urology clinics for two common urologic complaints. METHODS: We identified all PE-owned urology clinic locations as of June 2022 (n=390). For each PE-owned location, a geographically matched, non-PE owned clinic was identified. Each office was called using a "secret shopper" method with a standardized script, requesting an appointment on behalf of their Medicare-aged father for evaluation of gross hematuria or elevated prostate specific antigen (PSA). The primary outcome was appointment availability, and the secondary outcome was wait time until soonest appointment. RESULTS: PE-owned and non-PE-owned clinics treated the presenting complaints with similar frequency (gross hematuria: 85% v. 88%, p=0.3, elevated PSA: 93% v. 94%, p=0.5). Wait time in days until the next available appointment was similar for PE-owned clinics compared to non-PE clinics for both complaints (gross hematuria: 16 v. 13, p=0.06, elevated PSA: 18 v. 19, p=0.7). If available, the time in days until the soonest next appointment with an advanced practice provider was also similar between PE-owned and non-PE clinics (gross hematuria: 13 v. 11, p=0.07, elevated PSA: 13 v. 12, p=0.6). CONCLUSIONS: Overall, there were no large scale differences in access to outpatient urologic care between PE-owned clinics and non-PE owned clinics. Access to care in PE-owned clinics is likely clinically similar to geographic-matched controls for Medicare patients with gross hematuria or elevated PSA.

The characteristics of CTCF binding sequences contribute to enhancer blocking activity.

While the elements encoding enhancers and promoters have been relatively well studied, the full spectrum of insulator elements which bind the CCCTC binding factor (CTCF), is relatively poorly characterized. This is partly due to the genomic context of CTCF sites greatly influencing their roles and activity. Here we have developed an experimental system to determine the ability of minimal, consistently sized, individual CTCF elements to interpose between enhancers and promoters and thereby reduce gene expression during differentiation. Importantly, each element is tested in the identical location thereby minimising the effect of genomic context. We found no correlation between the ability of CTCF elements to block enhancer-promoter activity with the degree of evolutionary conservation; their resemblance to the consensus core sequences; or the number of CTCF core motifs harboured in the element. Nevertheless, we have shown that the strongest enhancer-promoter blockers include a previously described bound element lying upstream of the CTCF core motif. In addition, we found other uncharacterised DNaseI footprints located close to the core motif that may affect function. We have developed an assay of CTCF sequences which will enable researchers to sub-classify individual CTCF elements in a uniform and unbiased way.

Controversies in prostate cancer screening.

Prostate cancer is the second most diagnosed cancer and the fifth leading cause of cancer death among men worldwide. In the 1980s, the development and implementation of Prostate-Specific Antigen (PSA) testing for diagnosing prostate cancer led to a surge in the number of prostate cancer diagnoses. We explore the trends in recommendations and new innovations in adjunctive testing for prostate cancer screening.

Stereotactic Body Radiation Adoption Impacts Prostate Cancer Treatment Patterns.

OBJECTIVES: To investigate stereotactic body radiation (SBRT) adoption for prostate cancer. As evidence supporting SBRT mounts, its utilization and impact relative to other prostate cancer treatments is unknown. METHODS: We used SEER-Medicare to identify patients diagnosed with localized prostate cancer from 2008-2017. We then identified physician networks by identifying the primary treating physician of each patient based on primary treatment, then linking each physician to a practice. We examined trends in prostate cancer treatment between networks performing SBRT or not using chi-squared tests and logistic regression models. RESULTS: There were 35,972 patients who received treatment for prostate cancer at 234 physician networks. Of these patients, 30,635 were treated in a non-SBRT network (n=190), while 5,337 received treatment in a SBRT network (n=44). Patients who received care in an SBRT network were more likely to live in metropolitan areas ≥1 million (70% v. 46%, p<0.001), have a higher median income >$60,000 (62% v. 42%, p<0.001), and live in the northeast (35% v. 12%) or west (40% v. 38%, p<0.001) compared to non-SBRT networks. In SBRT networks, more patients received IMRT (31% v. 23%), and fewer patients received prostatectomy (16% v. 23%) or active surveillance (15% v. 19%) compared to non-SBRT networks. Black men were 45% less likely to receive SBRT (OR=0.55, CI-0.36-0.85) compared to White men. CONCLUSIONS: SBRT utilization is increasing relative to other prostate cancer treatments. Prostate cancer treatment mix is different in networks that offer SBRT, and SBRT is less available to some patient groups, raising concern for novel treatment inequity.

Mutagenesis on a complex mouse genetic background by site-specific nucleases.

Mouse models with complex genetic backgrounds are increasingly used in preclinical research to accurately model human disease and to enable temporal and cell-specific evaluation of genetic manipulations. Backcrossing mice onto these complex genetic backgrounds takes time and leads to significant wastage of animals. In this study, we aimed to evaluate whether site-specific nucleases could be used to generate additional genetic mutations in a complex genetic background, using the REVERSA mouse model of atherosclerosis, a model harbouring four genetically altered alleles. The model is comprised of a functional null mutation in the Ldlr gene in combination with a ApoB100 allele, which, after high-fat diet, leads to the rapid development of atherosclerosis. The regression of the pathology is achieved by inducible knock-out of the Mttp gene. Here we report an investigation to establish if microinjection of site-specific nucleases directly into zygotes prepared from the REVERSA could be used to investigate the role of the ATP binding cassette transporter G1 (ABCG1) in atherosclerosis regression. We show that using this approach we could successfully generate two independent knockout lines on the REVERSA background, both of which exhibited the expected phenotype of a significant reduction in cholesterol efflux to HDL in bone marrow-derived macrophages. However, loss of Abcg1 did not impact atherosclerosis regression in either the aortic root or in aortic arch, demonstrating no important role for this transporter subtype. We have demonstrated that site-specific nucleases can be used to create genetic modifications directly onto complex disease backgrounds and can be used to explore gene function without the need for laborious backcrossing of independent strains, conveying a significant 3Rs advantage.

Overarching Priorities for Health and Care Research in the United Kingdom: A Coproduced Synthesis of James Lind Alliance 'Top 10s'.

INTRODUCTION: James Lind Alliance (JLA) Priority Setting Partnerships (PSPs) produce 'Top 10' lists of health and care research priorities through a structured, shared decision-making process with patients or service users, carers and health or care professionals who identify questions that are most important to them. To date, over 150 PSPs in different areas of health and care have published research priorities. Some PSPs share similar priorities, which could be combined, promoted and addressed through collaborative research to increase value and reduce research waste. AIM: The aim of this study was to identify overarching themes common to JLA PSP priorities across different areas of health and care. METHODS: Our analysis included 'Top 10' research priorities produced by UK-based JLA PSPs between 2016 and 2020. The priorities were coded deductively by the Health Research Classification System (HRCS) health category and research activity. We then carried out online workshops with patients, service users and carers to generate new codes not already captured by this framework. Within each code, multistakeholder inductive thematic analysis was used to identify overarching themes, defined as encompassing priorities from three or more PSPs covering two or more health categories. We used codesign methods to produce an interactive tool for end users to navigate the overarching themes. RESULTS: Five hundred and fifteen research priorities from 51 PSPs were included in our analysis. The priorities together encompassed 20 of 21 HRCS health categories, the most common being 'generic health relevance' (22%), 'mental health' (18%) and 'musculoskeletal' (14%). We identified 89 overarching themes and subthemes, which we organised into a hierarchy with seven top-level themes: quality of life, caregivers and families, causes and prevention, screening and diagnosis, treatment and management, services and systems and social influences and impacts. CONCLUSION: There are many overarching themes common to research priorities across multiple areas of health and care. To facilitate new research and research funding, we have developed an interactive tool to help researchers, funders and patients or service users to explore these priority topics. This is freely available to download online. PATIENT OR PUBLIC CONTRIBUTION: Patients or service users and carers were involved throughout the study, including deciding the aims, designing the study, analysing priorities to identify themes, interpreting and reporting the findings.

Naturally sterile Mus spretus hybrids are suitable for the generation of pseudopregnant embryo transfer recipients.

For the preparation of embryo transfer recipients, surgically vasectomized mice are commonly used, generated by procedures associated with pain and discomfort. Sterile transgenic strains provide a nonsurgical replacement, but their maintenance requires breeding and genotyping procedures. We have previously reported the use of naturally sterile STUSB6F1 hybrids for the production of embryo transfer recipients and found the behavior of these recipients to be indistinguishable from those generated by vasectomized males. The method provides two substantial 3R impacts: refinement (when compared with surgical vasectomy) and reduction in breeding procedures (compared with sterile transgenic lines). Despite initial promise, the 3Rs impact of this innovation was limited by difficulties in breeding the parental STUS/Fore strain, which precluded the wider distribution of the sterile hybrid. The value of a 3R initiative is only as good as the uptake in the community. Here we, thus, select a different naturally sterile hybrid, generated from strains that are widely available: the B6SPRTF1 hybrid between C57BL/6J and Mus spretus. We first confirmed its sterility by sperm counting and testes weight and then trialed the recovery of cryopreserved embryos and germplasm within three UK facilities. Distribution of sperm for the generation of these hybrids by in vitro fertilization was found to be the most robust distribution method and avoided the need to maintain a live M. spretus colony. We then tested the suitability of B6SPRTF1 sterile hybrids for the generation of embryo transfer recipients at these same three UK facilities and found the hybrids to be suitable when compared with surgical vasectomized mice and a sterile transgenic strain. In conclusion, the potential 3Rs impact of this method was confirmed by the ease of distribution and the utility of sterile B6SPRTF1 hybrids at independent production facilities.

Finite Element Analysis for Degenerative Cervical Myelopathy: Scoping Review of the Current Findings and Design Approaches, Including Recommendations on the Choice of Material Properties.

BACKGROUND: Degenerative cervical myelopathy (DCM) is a slow-motion spinal cord injury caused via chronic mechanical loading by spinal degenerative changes. A range of different degenerative changes can occur. Finite element analysis (FEA) can predict the distribution of mechanical stress and strain on the spinal cord to help understand the implications of any mechanical loading. One of the critical assumptions for FEA is the behavior of each anatomical element under loading (ie, its material properties). OBJECTIVE: This scoping review aims to undertake a structured process to select the most appropriate material properties for use in DCM FEA. In doing so, it also provides an overview of existing modeling approaches in spinal cord disease and clinical insights into DCM. METHODS: We conducted a scoping review using qualitative synthesis. Observational studies that discussed the use of FEA models involving the spinal cord in either health or disease (including DCM) were eligible for inclusion in the review. We followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. The MEDLINE and Embase databases were searched to September 1, 2021. This was supplemented with citation searching to retrieve the literature used to define material properties. Duplicate title and abstract screening and data extraction were performed. The quality of evidence was appraised using the quality assessment tool we developed, adapted from the Newcastle-Ottawa Scale, and shortlisted with respect to DCM material properties, with a final recommendation provided. A qualitative synthesis of the literature is presented according to the Synthesis Without Meta-Analysis reporting guidelines. RESULTS: A total of 60 papers were included: 41 (68%) "FEA articles" and 19 (32%) "source articles." Most FEA articles (33/41, 80%) modeled the gray matter and white matter separately, with models typically based on tabulated data or, less frequently, a hyperelastic Ogden variant or linear elastic function. Of the 19 source articles, 14 (74%) were identified as describing the material properties of the spinal cord, of which 3 (21%) were considered most relevant to DCM. Of the 41 FEA articles, 15 (37%) focused on DCM, of which 9 (60%) focused on ossification of the posterior longitudinal ligament. Our aggregated results of DCM FEA indicate that spinal cord loading is influenced by the pattern of degenerative changes, with decompression alone (eg, laminectomy) sufficient to address this as opposed to decompression combined with other procedures (eg, laminectomy and fusion). CONCLUSIONS: FEA is a promising technique for exploring the pathobiology of DCM and informing clinical care. This review describes a structured approach to help future investigators deploy FEA for DCM. However, there are limitations to these recommendations and wider uncertainties. It is likely that these will need to be overcome to support the clinical translation of FEA to DCM.

Radiological Progression of Degenerative Cervical Myelopathy in a Clinically Stable Patient: Case Report.

Degenerative cervical myelopathy (DCM) is a common neurological condition, with disease progression that is both variable and difficult to predict. Here, we present a case of DCM in a gentleman in his late 60s with significant radiological disease progression without consequent change in clinical symptoms. The case serves as a reminder of an enduring medical aphorism that clinical history and examination should be prioritized above more complex data, such as imaging investigations. In addition, the case also highlights that guidelines should be contextualized within individual clinical circumstances.

Seniority of Surgeon in Chronic Subdural Hematoma Recurrence: A Systematic Review and Meta-analysis.

Chronic subdural hematoma (CSDH) is increasingly common, particularly in the older and multimorbid population. Surgical proficiency in management is required in the early years of U.K. neurosurgical training with most cases performed by nonconsultant-grade surgeons. The aim of this systematic review was to examine the effect of surgeon seniority on recurrence for patients with CSDH. Full-text articles comparing surgical treatment for CSDH with a "senior" (consultant/attending level) or "junior" (resident/registrar or similar) lead surgeon were identified. MEDLine and EMBASE databases were searched. The primary outcome of this study was recurrence. Secondary outcomes included postoperative complications and mortality rate. A random effects meta-analysis was performed. The risk of bias was assessed using the National Institute of Health risk of bias toolkit. Five studies were included in the final analysis (n = 941 total patients). Individually, no study identified a significant difference in recurrence rate and postoperative complications between senior and junior neurosurgeons. On meta-analysis, junior-led evacuations had lower recurrence rates on pooled univariable analysis (12.0% vs. 17.9% [odds ratio 0.48, 95% confidence interval 0.29-0.78, I2 = 0%]) (3 studies). Seniority of surgeon was not associated with increased rates of recurrence patients undergoing CSDH surgery. Complexity of operation may be a confounding factor in observed lower recurrence rates with more junior operators.

Cost-effectiveness of surgery for degenerative cervical myelopathy in the United Kingdom.

PURPOSE: Degenerative cervical myelopathy (DCM) is the commonest cause of adult spinal cord dysfunction worldwide, for which surgery is the mainstay of treatment. At present, there is limited literature on the costs associated with the surgical management of DCM, and none from the United Kingdom (UK). This study aimed to evaluate the cost-effectiveness of DCM surgery within the National Health Service, UK. MATERIALS AND METHODS: Incidence of DCM was identified from the Hospital Episode Statistics (HES) database for a single year using five ICD-10 diagnostic codes to represent DCM. Health Resource Group (HRG) data was used to estimate the mean incremental surgery (treatment) costs compared to non-surgical care, and the incremental effect (quality adjusted life year (QALY) gain) was based on data from a previous study. A cost per QALY value of <£30,000/QALY (GBP) was considered acceptable and cost-effective, as per the National Institute for Health and Clinical Excellence (NICE) guidance. A sensitivity analysis was undertaken (±5%, ±10% and ±20%) to account for variance in both the cost of admission and QALY gain. RESULTS: The total number of admissions for DCM in 2018 was 4,218. Mean age was 62 years, with 54% of admissions being of working age (18-65 years). The overall estimated cost of admissions for DCM was £38,871,534 for the year. The mean incremental (per patient) cost of surgical management of DCM was estimated to be £9,216 (ranged £2,358 to £9,304), with a QALY gain of 0.64, giving an estimated cost per QALY value of £14,399/QALY. Varying the QALY gain by ±20%, resulted in cost/QALY figures between £12,000 (+20%) and £17,999 (-20%). CONCLUSIONS: Surgery is estimated to be a cost-effective treatment of DCM amongst the UK population.

In the Murine and Bovine Maternal Mammary Gland Signal Transducer and Activator of Transcription 3 is Activated in Clusters of Epithelial Cells around the Day of Birth.

Signal transducers and activators of transcription (STAT) proteins regulate mammary development. Here we investigate the expression of phosphorylated STAT3 (pSTAT3) in the mouse and cow around the day of birth. We present localised colocation analysis, applicable to other mammary studies requiring identification of spatially congregated events. We demonstrate that pSTAT3-positive events are multifocally clustered in a non-random and statistically significant fashion. Arginase-1 expressing cells, consistent with macrophages, exhibit distinct clustering within the periparturient mammary gland. These findings represent a new facet of mammary STAT3 biology, and point to the presence of mammary sub-microenvironments.

Reliability of a Smartphone App to Objectively Monitor Performance Outcomes in Degenerative Cervical Myelopathy: Observational Study.

BACKGROUND: Developing new clinical measures for degenerative cervical myelopathy (DCM) is an AO Spine RECODE-DCM Research, an international and multi-stakeholder partnership, priority. Difficulties in detecting DCM and its changes cause diagnostic and treatment delays in clinical settings and heightened costs in clinical trials due to elevated recruitment targets. Digital outcome measures can tackle these challenges due to their ability to measure disease remotely, repeatedly, and more economically. OBJECTIVE: The aim of this study is to assess the reliability of the MoveMed battery of performance outcome measures. METHODS: A prospective observational study in decentralized secondary care was performed in England, United Kingdom. The primary outcome was to determine the test-retest reliability of the MoveMed performance outcomes using the intraclass correlation (ICC) of agreement . The secondary outcome was to determine the measurement error of the MoveMed performance outcomes using both the SE of the mean (SEM) of agreement and the smallest detectable change (SDC) of agreement . Criteria from the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) manual were used to determine adequate reliability (ie, ICC of agreement ≥0.7) and risk of bias. Disease stability was controlled using 2 minimum clinically important difference (MCID) thresholds obtained from the literature on the patient-derived modified Japanese Orthopaedic Association (p-mJOA) score, namely, MCID ≤1 point and MCID ≤2 points. RESULTS: In total, 7 adults aged 59.5 (SD 12.4) years who live with DCM and possess an approved smartphone participated in the study. All tests demonstrated moderate to excellent test-retest coefficients and low measurement errors. In the MCID ≤1 group, ICC of agreement values were 0.84-0.94 in the fast tap test, 0.89-0.95 in the hold test, 0.95 in the typing test, and 0.98 in the stand and walk test. SEM of agreement values were ±1 tap, ±1%-3% stability score points, ±0.06 keys per second, and ±10 steps per minute, respectively. SDC of agreement values were ±3 taps, ±4%-7% stability score points, ±0.2 keys per second, and ±27 steps per minute, respectively. In the MCID ≤2 group, ICC of agreement values were 0.61-0.91, 0.75-0.77, 0.98, and 0.62, respectively; SEM of agreement values were ±1 tap, ±2%-4% stability score points, ±0.06 keys per second, and ±10 steps per minute, respectively; and SDC of agreement values were ±3-7 taps, ±7%-10% stability score points, ±0.2 keys per second, and ±27 steps per minute, respectively. Furthermore, the fast tap, hold, and typing tests obtained sufficient ratings (ICC of agreement ≥0.7) in both MCID ≤1 and MCID ≤2 groups. No risk of bias factors from the COSMIN Risk of Bias checklist were recorded. CONCLUSIONS: The criteria from COSMIN provide "very good" quality evidence of the reliability of the MoveMed tests in an adult population living with DCM.

Mapping the Degenerative Cervical Myelopathy Research Landscape: Topic Modeling of the Literature.

STUDY DESIGN: Topic modeling of literature. OBJECTIVES: Our study has 2 goals: (i) to clarify key themes in degenerative cervical myelopathy (DCM) research, and (ii) to evaluate the current trends in the popularity or decline of these topics. Additionally, we aim to highlight the potential of natural language processing (NLP) in facilitating research syntheses. METHODS: Documents were retrieved from Scopus, preprocessed, and modeled using BERTopic, an NLP-based topic modeling method. We specified a minimum topic size of 25 documents and 50 words per topic. After the models were trained, they generated a list of topics and corresponding representative documents. We utilized linear regression models to examine trends within the identified topics. In this context, topics exhibiting increasing linear slopes were categorized as "hot topics," while those with decreasing slopes were categorized as "cold topics". RESULTS: Our analysis retrieved 3510 documents that were classified into 21 different topics. The 3 most frequently occurring topics were "OPLL" (ossification of the posterior longitudinal ligament), "Anterior Fusion," and "Surgical Outcomes." Trend analysis revealed the hottest topics of the decade to be "Animal Models," "DCM in the Elderly," and "Posterior Decompression" while "Morphometric Analyses," "Questionnaires," and "MEP and SSEP" were identified as being the coldest topics. CONCLUSIONS: Our NLP methodology conducted a thorough and detailed analysis of DCM research, uncovering valuable insights into research trends that were otherwise difficult to discern using traditional techniques. The results provide valuable guidance for future research directions, policy considerations, and identification of emerging trends.

An ovine model for investigation of the microenvironment of the male mammary gland.

The specific biology of the male breast remains relatively unexplored in spite of the increasing global prevalence of male breast cancer. Delineation of the microenvironment of the male breast is restricted by the low availability of human samples and a lack of characterisation of appropriate animal models. Unlike the mouse, the male ovine gland persists postnatally. We suggest that the male ovine mammary gland constitutes a promising adjunctive model for the male breast. In this study, we evaluate the male ovine mammary gland microenvironment, comparing intact and neutered males. Assessment of the glandular histo-anatomy highlights the resemblance of the male gland to that of neonatal female sheep and confirms the presence of rudimentary terminal duct lobular units. Irrespective of neutered status, cell proliferation in epithelial and stromal compartments is similarly low in males, and cell proliferation in epithelial cells and in the intralobular stroma is significantly lower than in pubertal female sheep. Between 42% and 72% of the luminal mammary epithelial cells in the male gland express the androgen receptor and expression is significantly reduced by neutering. Luminal epithelial cells within the intact and neutered male gland also express oestrogen receptor alpha, but minimal progesterone receptor expression is observed. The distribution of leukocytes within the ducts and stroma is similar to the mammary gland of female sheep and females of other species. Both macrophages and T lymphocytes are intercalated in the epithelial bilayer and are more abundant in the intralobular stroma than the interlobular stroma, suggesting that they may have a protective immunological function within the vestigial glandular tissue of the male sheep. Mast cells are also observed within the stroma. These cells cluster near the glandular tissue and are frequently located adjacent to blood vessels. The abundance of mast cells is significantly higher in intact males compared to neutered males, suggesting that hormone signalling may impact mast cell recruitment. In this study, we demonstrate the utility of the male ovine mammary gland as a model for furthering our knowledge of postnatal male mammary biology.

Variation of practice in the treatment of pyogenic spondylodiscitis: a European Association of Neurosurgical Societies Spine Section study.

OBJECTIVE: The incidence of spondylodiscitis is rising across Europe, but the ideal treatment approach remains controversial. The choice between conservative and surgical therapies is ambiguous due to a lack of consensus. This European survey aimed to explore prevailing treatment paradigms for primary spondylodiscitis. METHODS: Spine neurosurgeons were invited through the European Association of Neurosurgical Societies Spine Section's mailing list to participate in an online survey featuring 7 spondylodiscitis case vignettes. Along with general management queries, specific patient treatment questions were posed. Data analysis was performed using R software (version 4.0.4). The index of qualitative variation (IQV) was calculated to quantify the variability in responses. RESULTS: A total of 130 responses were collected, comprising 86.9% board-certified neurosurgeons and 13.1% neurosurgeons in training, with an average of 11 years of practice. Most respondents performed 50-100 spine surgeries annually, with 66.7% specializing in spine surgery. An epidural empyema causing pronounced neurological deficits influenced 95.4% toward a surgical intervention, and mild neurological deficits and challenges in pathogen identification prompted 72.3% and 80%, respectively, to consider a surgical approach. Vertebral body destruction and spinal deformity directed 60% and 66.2%, respectively, toward surgery, whereas advanced age and comorbidities had a much smaller impact-5.4% and 9.2%, respectively. Clinical vignettes highlighted a predominant preference for conservative treatment in specific cases, with statistical significance (p < 0.05). The IQV values evaluated for each question ranged from 0.88 to 0.99, indicating low agreement across all questions among respondents. When examining the average IQV by country, intercountry variations in IQV were substantial, as illustrated by the diverse range of overall mean IQV values (0.15-0.85). CONCLUSIONS: The findings reveal a significant variability in the treatment of spondylodiscitis among European neurosurgeons, with most neurosurgeons opting for conservative treatment. These diverse strategies, both between and within countries, highlight an imperative for evidence-backed guidelines and consensus statements for this grave condition.

Frequent disturbances enhanced the resilience of past human populations.

The record of past human adaptations provides crucial lessons for guiding responses to crises in the future1-3. To date, there have been no systematic global comparisons of humans' ability to absorb and recover from disturbances through time4,5. Here we synthesized resilience across a broad sample of prehistoric population time-frequency data, spanning 30,000 years of human history. Cross-sectional and longitudinal analyses of population decline show that frequent disturbances enhance a population's capacity to resist and recover from later downturns. Land-use patterns are important mediators of the strength of this positive association: farming and herding societies are more vulnerable but also more resilient overall. The results show that important trade-offs exist when adopting new or alternative land-use strategies.