Nevin Manimala

Theriogenology. 2026 Jun 30;265:118056. doi: 10.1016/j.theriogenology.2026.118056. Online ahead of print.

ABSTRACT

This study aimed to investigate the potential role of 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) in steroidogenesis and its possible involvement in germ cell development and meiotic initiation in ducks. Primordial germ cells (PGCs) were isolated from duck embryos and characterized by epithelioid adherent morphology, with more than 90% of cells showing positive expression of c-kit. Functional analyses indicated that overexpression of 17β-HSD3 was associated with increased PGC proliferation (48 h, P < 0.05; 72 h, P < 0.01) and reduced apoptosis (P < 0.0001). In addition, 17β-HSD3 overexpression was correlated with a numerical increase in AKR1D1 expression (P > 0.05) and a significant decrease in P450scc expression (P < 0.001). Retinoic acid (RA) treatment (0.25-1 μM) showed a tendency toward cell cycle progression, as reflected by a decrease in the G0/G1 phase population and an increase in S phase cells, although these changes did not reach statistical significance (P > 0.05). Furthermore, RA exposure was significantly associated with increased expression of 17β-HSD3, Cvh, and Stra8, and decreased expression of pluripotency-associated genes Itga6 and Sox2 (P < 0.001 or P < 0.0001), suggesting molecular changes consistent with meiotic entry. Collectively, these results suggest that 17β-HSD3 may be involved in the modulation of steroidogenesis-related gene expression in duck germ cells and is associated with germ cell proliferation and meiotic initiation. This study provides preliminary evidence that may contribute to the understanding of molecular mechanisms underlying avian germ cell development and reproductive regulation in poultry.

PMID:42385267 | DOI:10.1016/j.theriogenology.2026.118056

Neurosurg Focus. 2026 Jul 1;61(1):E4. doi: 10.3171/2026.3.FOCUS2617.

ABSTRACT

OBJECTIVE: The aim of this study was to determine the risks of reoperations for adjacent segment disease (ASD) and all causes between 1-level cervical disc arthroplasty (CDA) and 1-level anterior cervical discectomy and fusion (ACDF) and 2-level CDA and 2-level ACDF using meta-analysis. This study was specifically designed to address several key methodological limitations of prior meta-analyses, including cohort duplication, short follow-up duration, non-level-matched pooling of 1-level and 2-level procedures, and exclusion of international randomized controlled trials (RCTs).

METHODS: Using PRISMA guidelines, the authors performed a thorough search of the PubMed, Embase, and Scopus databases from January 2012 through November 2025. Studies were restricted to FDA investigational device exemption (IDE) trials and international RCTs with > 5 years of follow-up. Direct pairwise meta-analyses were conducted, and odds ratios and standard errors were calculated for outcomes. Random-effects pooling was performed, and between-study heterogeneity was assessed using Cochran’s Q statistic and the I2 statistic.

RESULTS: A total of 1756 studies were identified from the databases with 199 studies available for full review. Sixteen studies were selected for the analysis. For ASD reoperations in 13 studies, the authors found that 1-level CDA was associated with an approximately 55% lower odds of reoperation for ASD compared with 1-level ACDF (OR 0.45, 95% CI 0.29-0.69; p < 0.001). For 2-level CDA, there was a 49% lower chance of having an ASD reoperation compared with 2-level ACDF (OR 0.51, 95% CI 0.30-0.87; p = 0.013). Similarly, in 14 studies, there was a statistically significant reduction in the odds of all-cause reoperations in 1-level CDA compared with ACDF (OR 0.58, 95% CI 0.42-0.80; p = 0.001) while for 2-level CDAs there was a 52% lower chance of all-cause reoperations compared with 2-level ACDFs (OR 0.48, 95% CI 0.32-0.72; p < 0.001).

CONCLUSIONS: In this comprehensive, level-matched meta-analysis of FDA IDE studies and international RCTs in which we addressed several key methodological limitations of prior meta-analyses, we found that 1-level and 2-level CDAs were associated with a consistent reduction in reoperation risks compared with ACDF for ASD and all-cause reoperations with a mean 7-year follow-up. Future investigations leveraging large, prospective registries will be essential to determine the generalizability of IDE studies and international RCTs to the broader clinical populations.

PMID:42385252 | DOI:10.3171/2026.3.FOCUS2617

Neurosurg Focus. 2026 Jul 1;61(1):E3. doi: 10.3171/2026.3.FOCUS251150.

ABSTRACT

OBJECTIVE: The aim of this study was to determine if there is a difference in reoperations for adjacent segment disease (ASD) and all-cause reoperations between 1-level and contiguous 2-level cervical disc arthroplasty (CDA).

METHODS: A retrospective cohort study was conducted on patients (18-60 years of age) with cervical degenerative disc disease who underwent a primary 1-level or 2-level CDA using data from a national spine registry. Cox proportional hazards regression was used to evaluate reoperations for all-cause risks. Hazard ratios (HRs) and 95% confidence intervals are presented; a p value < 0.05 was the significance threshold.

RESULTS: The cohort consisted of 650 patients with 1-level CDA and 159 patients with 2-level CDA. The mean overall observational follow-up was 6.2 years (SD 4.3 years) for 1-level CDA and 4.2 years (SD 3.1 years) for 2-level CDA. The 5-year incidence of ASD reoperations was higher in 1-level CDA (4.7%, 95% CI 2.8%-6.6%) compared to 2-level CDA (1.1%, 95% CI 0.0%-3.15%). In Cox regression analysis, there was no statistical difference in all-cause reoperations between 1-level CDA and 2-level CDA (HR 0.93, 95% CI 0.44-1.94; p = 0.84). Few events in 2-level ASD reoperations allowed determination of hazard ratio.

CONCLUSIONS: This study is the first large real-world analysis outside of investigational device exemption trials to show no significant difference in all-cause reoperation rates between 1-level and 2-level CDA. Notably, the 5-year incidence of ASD-related reoperations was substantially higher following 1-level CDA compared with 2-level CDA. The reason for this discrepancy remains unclear. One possibility is surgeon selection bias-where an adjacent degenerative level may be left untreated during a 1-level CDA under the assumption that motion preservation would protect against adjacent segment deterioration. Alternatively, the higher ASD rate may simply reflect the natural history of cervical spondylosis rather than device effect. Further investigation is needed to determine the true drivers of this observation.

PMID:42385245 | DOI:10.3171/2026.3.FOCUS251150

Neurosurg Focus. 2026 Jul 1;61(1):E9. doi: 10.3171/2026.3.FOCUS251207.

ABSTRACT

OBJECTIVE: Anterior cervical disc arthroplasty offers theoretical advantages over fusion such as quicker recovery and decreased biomechanical stress at adjacent levels. However, anterior cervical discectomy and fusion (ACDF) may be beneficial for patients with dynamic instability or advanced spondylosis. In patients with multilevel cervical degenerative disc disease, anterior cervical hybrid arthroplasty-fusion (ACHAF) constructs may allow for personalized approaches, addressing level-specific pathology while offering other theoretical advantages such as requiring a shorter anterior plate (if utilized), potentially reducing complications and risk of dysphagia. The authors aimed to evaluate radiographic outcomes and early safety of ACHAF compared with ACDF.

METHODS: This is a single-center retrospective study of patients who underwent 2- or 3-level ACHAF or ACDF between January 2021 and May 2025 by the senior author. In the ACHAF group, arthroplasty was performed at the most cephalad level. Radiographic parameters (C2-7 lordosis, C2-7 sagittal vertical axis [cSVA], and Cobb angle and height of the disc immediately proximal to the construct) were assessed preoperatively and at 6 months postoperatively. Clinical outcomes included length of stay and rates of return to the emergency department (ED) within 90 days, complications, dysphagia at 6 months postoperatively, and reoperation during the study period.

RESULTS: A total of 66 patients met the study criteria: 23 underwent ACHAF and 43 underwent ACDF (mean age 57.9 years). There was no difference in change of C2-7 lordosis or cSVA. The ACHAF group exhibited a decreased adjacent disc Cobb angle and increased disc height postoperatively, whereas the ACDF group exhibited an increased disc Cobb angle and decreased disc height (p < 0.001). Dysphagia at 6 months was more frequent in ACDF patients (32.6% vs 8.7%, p = 0.04). There was no significant difference in reoperation rates during the study period. Complications (p = 0.29) were more common in the ACDF group, and return to ED was more frequent in the ACHAF group (p = 0.71), although these did not meet statistical significance. There was no difference in rates of discharge on postoperative day 1 (p > 0.99).

CONCLUSIONS: ACHAF constructs possibly reduce stress on the proximal unoperated motion segment due to adjacent load sharing from the arthroplasty. Furthermore, dysphagia at 6 months postoperatively was less prevalent in the ACHAF group. Additional studies are needed to determine if ACHAF is associated with differences in patient-reported outcomes or long-term differences in rates of dysphagia or reoperation.

PMID:42385243 | DOI:10.3171/2026.3.FOCUS251207

Neurosurg Focus. 2026 Jul 1;61(1):E12. doi: 10.3171/2026.3.FOCUS2624.

ABSTRACT

OBJECTIVE: The optimal surgical treatment for lumbar spinal stenosis (LSS) with degenerative spondylolisthesis (DS) remains controversial. Posterior lumbar facet arthroplasty preserves motion after decompression and may address some of the limitations of fusion techniques. The Total Posterior Spine System (TOPS) investigational device exemption trial compared decompression with facet arthroplasty to decompression plus fusion (open with interbody). This study reports the 3-year outcomes from this trial.

METHODS: This randomized, controlled, multicenter trial enrolled 321 patients with LSS and grade I DS across 37 sites (2:1 randomization of arthroplasty to fusion). Eligible patients were 35-80 years old, had failed ≥ 6 months of nonsurgical treatment, and met thresholds for disability and leg pain. The primary endpoint was a composite clinical success score at 36 months, defined by four criteria: 1) no reoperation or lumbar injection, 2) no major device adverse events, 3) ≥ 15-point improvement in the Oswestry Disability Index (ODI), and 4) no new/progressive neurological deficit. Secondary outcomes included the ODI score, visual analog scale (VAS) scores for back and leg pain, the Zurich Claudication Questionnaire (ZCQ), device-related adverse events, and reoperations.

RESULTS: One hundred seventy-nine patients in the arthroplasty (TOPS) group and 74 in the fusion group were eligible for the 36-month analysis. The composite clinical success achievement rate was significantly higher in the arthroplasty group (76.0%) than in the fusion group (56.8%; p = 0.0038). The rate of reoperation or lumbar injection was significantly lower for the arthroplasty group (14.0%) compared to the fusion group (25.3%; p = 0.0222). Arthroplasty was associated with a significantly higher minimal clinically important difference (MCID) achievement rate for VAS back pain score compared with fusion (85.2% vs 72.2%; p = 0.041). Although there was no significant difference in ODI score, VAS leg pain score, or ZCQ component scores between groups, the arthroplasty group trended toward higher MCID achievement rates across all patient-reported outcome measures. There was no significant difference in reoperation failure rates between groups (5.8% for arthroplasty vs 9.5% for fusion; p = 0.329).

CONCLUSIONS: Decompression and dynamic stabilization with lumbar facet arthroplasty was associated with statistically significantly superior clinical outcomes and lower rates of secondary invasive procedures, including reoperations and injections, compared with decompression and fusion. Long-term follow-up is critical in defining the role of lumbar facet arthroplasty for the treatment of DS.

PMID:42385242 | DOI:10.3171/2026.3.FOCUS2624

Stat Med. 2026 Jul;45(15-17):e70647. doi: 10.1002/sim.70647.

ABSTRACT

Dependent censoring, common in medical studies with informative dropout, invalidates standard Cox regression by violating the independent censoring assumption. While copula-based methods offer flexible dependence modeling, their parametric extensions face identifiability barriers. We address this problem through a novel fully identifiable parametric model that synergizes double-Cox marginal structures with copula dependence, which is called the copula-double-Cox model. Using Weibull or generalized exponential (GenExp) distributions, the double-Cox model links both scale and shape parameters to covariates via Cox-type regressions. This structure accommodates non-proportional hazards while containing the standard Cox model as a special case. We establish identifiability under dependent censoring and derive consistent estimators for baseline parameters, regression coefficients, and copula association. Simulations confirm robustness to association structure misspecification and over-parameterization. Estimation accuracy is supported by asymptotic theory and standard error evaluation via the observed information matrix. Finally, we illustrate the proposed approach through a real-world application to a dataset on monoclonal gammopathy of undetermined significance (MGUS), highlighting its practical relevance. The results show that our method provides an interpretable characterization of covariate effects on both failure time and censoring time through its double-Cox structure. An open-source R implementation of the copula-double-Cox model is provided on GitHub.

PMID:42385224 | DOI:10.1002/sim.70647

Early Interv Psychiatry. 2026 Jul;20(7):e70215. doi: 10.1111/eip.70215.

ABSTRACT

AIM: To evaluate the effectiveness of digital interventions in supporting young caregivers’ mental health, well-being, and caregiving experiences, and to assess implementation factors including adherence and acceptability.

METHOD: We systematically searched six databases (MEDLINE, Embase, PsycINFO, CINAHL, Cochrane Central, and Scopus) and grey literature sources from inception to March 2025, identifying studies evaluating digital interventions for caregivers aged 25 years or younger. Study selection, data extraction, and risk of bias assessment were conducted independently by two reviewers. Due to substantial heterogeneity, narrative synthesis was performed following the Synthesis Without Meta-analysis (SWiM) reporting guidelines.

RESULTS: From 752 records, six studies met inclusion criteria, comprising three randomized controlled trials, one feasibility study, and two development/adaptation studies. Interventions included web-based platforms, mobile applications, audio-conferencing systems, and e-learning platforms. Digital tools showed limited effectiveness for mental health outcomes but demonstrated promise for quality-of-life improvements, with one trial showing statistically significant results (Wilks’ λ = 0.95, F(4, 418) = 2.74, p = 0.03). Adherence varied dramatically between self-guided platforms (26%) and structured programs (93%). All RCTs demonstrated a high risk of bias.

DISCUSSION: These findings reveal a ‘digital paradox’ whereby the theoretical advantages of accessibility failed to translate into engagement without human facilitation. Digital interventions for young caregivers require hybrid models combining technological convenience with relational support, structured flexibility, and continuous co-design with young caregivers to optimize engagement and effectiveness. The limited number of included studies and uniformly high risk of bias across RCTs underscore the need for pragmatic trials with robust implementation evaluations.

PROSPERO REGISTRATION: CRD42024604175.

PMID:42385212 | DOI:10.1111/eip.70215

Int J Nurs Pract. 2026;32(4):e70162. doi: 10.1111/ijn.70162.

ABSTRACT

BACKGROUND: Health literacy and fear of disease progression can predict quality of life, yet the underlying mechanisms among these three factors remain poorly understood.

AIM: This study aimed to investigate the hypothesis that health literacy among patients with ischemic stroke is associated with fear of disease progression and both directly and indirectly influence quality of life through the mediating role of fear of disease progression.

METHODS: Between December 2023 and June 2024, questionnaires were distributed to 300 in-patients with ischemic stroke selected by convenience sampling from the neurology departments of three tertiary general hospitals in the Xiangxi region of Hunan Province. Assessments were conducted using the General Information Questionnaire, the Medical Outcomes Study Short Form 36 (SF-36), Health Literacy Management Scale (HeLMS) and Fear of Progression Questionnaire-Short Form (FoP-Q-SF). Pearson correlation analysis was employed to examine the correlations between variables; AMOS 24.0 statistical analysis software was used to explore the pathways and effect sizes of fear of disease progression and health literacy on quality of life.

RESULTS: Health literacy was positively correlated with quality of life (r = 0.412, p < 0.01), while fear of disease progression was negatively correlated with quality of life (r = -0.445, p < 0.01). Fear of disease progression partially mediated the relationship between health literacy and quality of life, accounting for 41.3% of the total effect.

CONCLUSIONS: Findings support the development of targeted psychosocial intervention strategies aimed at enhancing patients’ health literacy to effectively alleviate disease-related fear, ultimately improving quality of life and optimizing care outcomes for stroke patients.

PMID:42385192 | DOI:10.1111/ijn.70162

Stat Med. 2026 Jul;45(15-17):e70659. doi: 10.1002/sim.70659.

ABSTRACT

The current bedrock of precision prevention is selecting high-risk individuals for screening or other prevention services under the assumption that those at highest risk would have the highest benefit from prevention services. However, this may not hold when disease risk and competing mortality are highly correlated. In such cases, risk-based prevention may preferentially select older individuals with multiple comorbidities who would have substantially reduced life-years gainable from the service and increased risks of harm from any resulting surgical procedures. For such prevention services, we propose a benefit-based selection strategy in which individuals are selected according to their expected gain in life-years (i.e., difference in mean survival time with and without the prevention service). We estimate the expected gain in life-years for individuals in a target screening population by combining data from a randomized trial, which may not be population-representative, and data from a population-representative survey that has larger sample size, more covariates, and longer follow-up time to evaluate mortality than the trial. We derive the Taylor-linearized variances for the estimated expected gain in life-years that take into account the randomness due to both trial and survey sample. We show that benefit-based selection of ever-smokers for lung-cancer screening can identify individuals with more favorable benefit-harm trade-offs compared to risk-based selection. Using simulation studies, we examine the conditions in which one strategy may be preferable over the other.

PMID:42385157 | DOI:10.1002/sim.70659

Int J Inj Contr Saf Promot. 2026 Jul 1:1-16. doi: 10.1080/17457300.2026.2689077. Online ahead of print.

ABSTRACT

This paper explores historical and contemporary intersections between mass-mortality epidemics and violent crime in South Africa, focusing on four major epidemics – Spanish Flu, tuberculosis, HIV, and Covid-19. The study integrates epidemiological data and contextual historical information such as crime statistics, archival records, and secondary scholarship to explore whether epidemic-driven mortality crises are associated with subsequent changes in violence and injury profiles. With the possible exception of gendered violence, the study finds little evidence that earlier epidemics directly contributed to rapid or sustained increases in violent crime, despite causing substantial adult mortality and long-term social and economic disruption. A comparison between epidemic and socio-economic profiles strongly suggests that the significant increases in violent crime recorded after the Covid-19 pandemic are highly localised, and may be more strongly related to lockdown responses, including alcohol restrictions, rather than the effects of disease itself.

PMID:42385127 | DOI:10.1080/17457300.2026.2689077