Tag: nevin manimala

Beijing Da Xue Xue Bao Yi Xue Ban. 2026 Jun 18;58(3):479-489.

ABSTRACT

OBJECTIVE: To systematically investigate the associations between umbilical cord blood protein expression profiles and early infant neurodevelopment using a prospective birth cohort, to identify potential early biomarkers through high-throughput proteomics, and to explore underlying biological mechanisms, thereby providing scientific evidence for early identification of neurodevelopmental risks and understanding the molecular basis of neurodevelopmental deviations in general populations.

METHODS: Based on the Peking University Birth Cohort in Tongzhou, this study enrolled 96 children who completed ages and stages questionnaires, third edition (ASQ-3) assessments at 1 and 3 years of age. Participants were classified into an abnormal group (n=42) and a control group (n=54) according to ASQ-3 screening results. Non-targeted quantitative proteomics was performed on cryopreserved umbilical cord blood plasma samples collected at birth. Differential expression analysis, principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), and weighted gene co-expression network analysis (WGCNA) were conducted to identify differentially expressed proteins, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. The fold change (FC) was calculated. Independent samples t-test was used for statistical comparison, with Benjamini-Hochberg method applied to calculate false discovery rate (FDR) for multiple testing correction.

RESULTS: Proteomic analysis identified 8 214 common proteins, among which 385 proteins were differentially expressed (P < 0.05, |log₂FC| >0.585), including 189 proteins upregulated and 196 proteins downregulated in the abnormal group. PCA and OPLS-DA revealed systematic differences in protein expression patterns between the two groups. WGCN A identified 10 co-expression modules, with the yellow module showing significant negative correlation with ASQ-3 abnormal grouping (r=-0.233, P=0.024) and the pink module positively correlating with communication domain scores (r=0.342, P=0.003). Enrichment analyses demonstrated that differential proteins and key modules were primarily enriched in two functional categories: (1) genetic information processing pathways, including ribosome, spliceosome, and mRNA processing; and (2) cytoskeleton organization and Wnt signaling pathways. These pathways held significant biological relevance in the pathogenesis of neurodevelopmental disorders.

CONCLUSION: Perturbations in proteins associated with genetic information processing and cytoskeleton/Wnt signaling pathways in umbilical cord blood may represent important molecular characteristics of early neurodevelopmental screening abnormalities in infants. This study provides potential peripheral blood biomarker combinations for early identification of neurodevelopmental risks in general populations and offers novel insights into the biological mechanisms underlying neurodevelopmental deviations. Future research should validate these findings in larger-scale cohorts and elucidate specific functional mechanisms of key proteins through experimental studies.

PMID:42287041

Beijing Da Xue Xue Bao Yi Xue Ban. 2026 Jun 18;58(3):472-478.

ABSTRACT

OBJECTIVE: To assess the spatial accessibility of pediatric healthcare resources in Beijing and to develop an optimization model for resource allocation under a fixed additional resource constraint, with the aim of exploring optimal allocation strategies for 2025 and 2030.

METHODS: Using communities as the unit of analysis, this study integrated data on Beijing ‘ s child population in 2020 and pediatric healthcare resources in 2022. An improved two-step floating catchment area (2SFCA) method was applied to measure spatial accessibility. Based on projected child population data for 2025 and 2030, an optimization model was constructed to minimize regional disparities in accessibility. Under the constraint of a fixed total number of additional resources, optimal spatial allocation schemes were derived and compared with a conventional population-based allocation approach.

RESULTS: In 2022, Beijing had 4 704 pediatric beds and 4 011 pediatric physicians. The mean spatial accessibility for pediatric beds and pediatric physicians was 1.17 and 0.97, respectively, with a standard deviation of 2.78 for bed accessibility, exhibiting a clear spatial pattern of higher accessibility in central districts and lower accessibility in suburban districts. In the same year, the number of pediatric physicians per 1 000 children in Beijing reached 1.52, already exceeding the targets for 2025 and 2030; therefore, no additional increase in total physician numbers was required. Under the 2025 optimization scenario, the mean accessibility of pediatric beds increased to 1.68, with the standard deviation declining to 2.45, indicating a reduction in regional disparities. Under the 2030 scenario, the mean accessibility further increased to 2. 31, with a standard deviation of 2.56, reflecting continued improvement in accessibility. The optimization model identified Daxing District, Tongzhou District, and Mentougou District as priority districts for additional bed allocation, whereas the conventional population-based approach allocated more resources to Daxing District, Haidian District, and Tongzhou District. While the two approaches showed general consistency in overall spatial allocation, the optimization model more effectively addressed inter-district disparities in accessibility.

CONCLUSION: Significant spatial disparities were identified in the distribution of pediatric healthcare resources in Beijing. The accessibility-oriented optimization approach, under a fixed resource constraint, improved the alignment between supply and demand and reduced regional inequities. It served as a useful complement to conventional population-based allocation methods and provided quantitative evidence to support refined planning and dynamic adjustment of pediatric healthcare resources. Given that the total number of pediatric physicians has already met national targets, leveraging integrated medical consortium and multi-site practice policies to promote the mobility of qualified pediatric physicians toward underserved areas represents a promising pathway toward structural optimization of spatial resource distribution.

PMID:42287040

Beijing Da Xue Xue Bao Yi Xue Ban. 2026 Jun 18;58(3):437-445.

ABSTRACT

OBJECTIVE: To evaluate the impact of international pooled procurement mechanisms, which are primarily represented by the United Nations Children ‘ s Fund (UNICEF) and the Pan American Health Organization (PAHO), on the procurement prices of vaccines.

METHODS: Based on 14 497 vaccine procurement transaction records collected from 188 different countries spanning the period from 2013 to 2024, this research employed a high-dimensional fixed effects model along with an event study metho-dology to accurately identify the price effects and dynamic temporal trends, while simultaneously conducting a multidimensional heterogeneity analysis.

RESULTS: (1) The baseline model demonstrated that, when compared to the independent self-procurement conducted by individual nations, utilizing pooled procurement through the UNICEF significantly reduced the average vaccine prices by 27.6% (β=-0.323, P < 0.01). The PAHO mechanism similarly exhibited an initial price reduction potential of approximately 30.9% (β=-0.370, P=0.052). (2) The event study method strictly validated the parallel trend assumption (joint significance test of pre-treatment coefficients: F=0.27, P=0.845). Dynamic tracking revealed that a price reduction of approximately 30.0% (β=-0.356, P < 0.01) was achieved exactly in the year of transitioning from self-procurement to pooled procurement, and this reduction effect remained persistently stable in subsequent years. (3) Heterogeneity tests revealed a significant “pro-poor” effect of pooled procurement: the price reduction margin obtained by small-scale buyers (38.5%, β=-0.487, P < 0.01) was significantly higher than that of large-scale buyers (22.5%, β=-0.255, P < 0.01). The marginal price reduction coefficient for non-Global Alliance for Vaccines and Immunization (GAVI) eligible countries (β=-0.418, P < 0.01) was substantially larger than that for GAVI eligible countries (β=-0.118, P < 0.05). The high-income country group experienced the most substantial price drop (β=-0.475, P < 0.01). (4) The supply-side moderating effect analysis indicated that UNICEF’ s collective bargaining power maintained robustness across diverse market structures, showing no statistically significant attenuation despite increases in market concentration (interaction term β=0.095, P>0.10).

CONCLUSION: Institutionalized pooled procurement mechanisms are capable of significantly reducing vaccine prices. For those countries that are currently in the immunization financing transition period, as well as those facing high self-procurement benchmark prices, participating in an efficient international pooled procurement platform serves as a critical institutional arrangement to replace external financial aid and to effectively maintain the long-term affordability of vaccines.

PMID:42287036

Biomed Res Int. 2026;2026(1):e1619093. doi: 10.1155/bmri/1619093.

ABSTRACT

BACKGROUND: Systemic inflammation links periodontal disease (PD) and nephrolithiasis. Proinflammatory cytokines like IL-6, IL-8, TNF-α, IL-1β, and MMP-8 are implicated in both conditions. This study investigates salivary levels of these biomarkers in young adult males with kidney stones and their association with periodontal status (CPITN) and body mass index (BMI).

METHODS: This case-control study enrolled 109 males (25-35 years): 52 with kidney stones and 57 healthy controls. Unstimulated whole saliva was analyzed for IL-6, IL-8, TNF-α, IL-1β, and MMP-8 via ELISA. Periodontal health was assessed using the community periodontal index of treatment needs (CPITN). Serum C-reactive protein (CRP) and BMI were also measured.

RESULTS: The kidney stone group had significantly higher salivary IL-6 (3.95 [2.0-5.2] pg/mL vs. 2.7 [1.5-4.0] pg/mL; adj. p = 0.042) and TNF-α (11.99 [8.5-13.8] pg/mL vs. 9.5 [7.0-11.6] pg/mL; adj. p = 0.021) than controls. Differences in IL-1β (adj. p = 0.051) and MMP-8 (adj. p = 0.058) showed a consistent trend toward elevation but did not retain statistical significance after FDR correction. No significant difference was observed in salivary IL-8 levels (adj. p = 0.120). Patients also showed elevated CRP (p = 0.010) and worse CPITN scores (p = 0.002). In the kidney stone group, salivary IL-6, TNF-α, and MMP-8 positively correlated with CPITN scores (p < 0.01), whereas TNF-α also correlated with BMI (p = 0.048).

CONCLUSION: Elevated salivary inflammatory biomarkers (IL-6 and TNF-α) are significantly associated with kidney stones and periodontal status (CPITN) in young males, whereas IL-1β and MMP-8 showed a trend toward elevation. Salivary analysis may be a noninvasive tool for assessing systemic inflammation and identifying at-risk individuals.

PMID:42287034 | DOI:10.1155/bmri/1619093

Addiction. 2026 Jun 12. doi: 10.1111/add.70502. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Naltrexone is a pharmacotherapeutic option for relapse prevention in opioid use disorder (OUD); however, studies highlight low rates of initiation and high rates of discontinuation as limiting its effectiveness. We aimed to (1) estimate the percentage of individuals with OUD who (having undergone withdrawal and wish to remain abstinent) initiate and discontinue naltrexone and (2) examine participant- and study-level factors that contribute to variation in initiation and discontinuation rates.

METHODS: We undertook a systematic review, random-effects meta-analysis and meta-regression searching Medline, Embase, PsychINFO and CENTRAL from database inception to 19 February 2025 for studies of any design from any geographical region involving individuals with OUD eligible to receive naltrexone as a relapse prevention pharmacotherapy (i.e. those completing opioid withdrawal and wishing to remain abstinent). Measurements included the percentage of individuals who initiate or discontinue oral, long-acting injectable depot or implantable formulations of naltrexone at 1, 3 or 6 months. Certainty was assessed using the GRADE framework.

RESULTS: Twenty-two studies, including 124 016 individuals, reported initiation and 95 studies, including 16 969 individuals, reported discontinuation. The pooled percentage initiating oral naltrexone among those eligible was 60.3% [95% confidence interval (CI) = 38.9%-80.0%, 2014 participants, 15 studies] and depot was 18.2% (95% CI = 2.7%-42.5%, 57 383 participants, 4 studies). The pooled percentage discontinuing oral was 50.0% (95% CI = 41.9%-58.1%, 7340 participants, 34 studies) at 1 month, 61.3% (95% CI = 50.9%-71.2%, 2347 participants, 29 studies) at 3 months and 71.0% (95% CI = 57.3%-83.0%, 1889 participants, 19 studies) at 6 months. The pooled percentage discontinuing depot was 26.1% (95% CI = 19.5%-33.3%, 3589 participants, 33 studies) at 1 month, 46.7% (95% CI = 38.4%-55.1%, 3302 participants, 33 studies) at 3 months and 60.0% (95% CI = 43.2%-75.8%, 3071 participants, 22 studies) at 6 months. Statistically significantly higher percentages initiated oral naltrexone if it was the only offered pharmacotherapy (meta-regression coefficient 33.6%, 95% CI = 8.1%-59.2%, P = 0.014) and statistically significantly lower percentages discontinued oral naltrexone at 3 and 6 months if administration was supervised (meta-regression coefficient -18.6%, 95% CI = -36.6% to -1.0%, P = 0.043 and -27.3%, 95% CI = -50.1% to -4.4%, P = 0.022, respectively). There was no clear evidence that study setting (i.e. if the study was conducted in routine clinical care or an investigational setting) substantially explained or contributed to the variation in any estimates. All outcomes were very low certainty.

CONCLUSIONS: Very low certainty evidence suggests that, among people with opioid use disorder who have undergone withdrawal and wish to remain abstinent, a substantial percentage are willing to initiate naltrexone with marked early discontinuation.

PMID:42286437 | DOI:10.1111/add.70502

Addiction. 2026 Jun 12. doi: 10.1111/add.70503. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Individuals with opioid use disorder (OUD) frequently present with co-occurring mental health conditions such as depression and posttraumatic stress disorder (PTSD), along with other mental health substance use disorders, physical health conditions and social determinants that together comprise ‘clinical complexity.’ Collaborative care (CC), a primary care-based behavioral health integration model, aims to improve outcomes through coordinated, patient-centered treatment. This study examined heterogeneity in baseline clinical complexity among participants in the CLARO (Collaboration Leading to Addiction Treatment and Recovery from Other Stresses) trial and assessed whether the effects of CC versus enhanced usual care (EUC) differed across clinical complexity groups.

METHODS: Secondary analysis of CLARO, a pragmatic randomized clinical trial (n = 797) of CC versus EUC for adults with OUD and depression and/or PTSD, conducted in 18 low-resourced primary care clinics in New Mexico and California, USA. Latent class analysis of baseline data identified subgroups defined by mental health and substance use as the main characteristics along with physical health and social challenges. Six-month treatment effects were estimated using one-step models that jointly estimated latent class membership and class-specific outcomes, incorporating class × treatment interactions. Outcomes included depression symptom severity, PTSD symptom severity, and buprenorphine utilization and prescribing duration.

RESULTS: Three subgroups were identified: (1) low complexity (43%), with relative clinical and social stability; (2) mental health complexity (34%), with high psychiatric symptoms but lower substance use and moderate social adversity; and (3) high dual complexity (23%). Compared with EUC, CC was associated with lower depression severity at follow-up for the low-complexity class, but not for other classes. CC and EUC did not differ statistically significantly with respect to PTSD outcomes in any class. Buprenorphine utilization and prescribing duration outcomes were similar across CC and EUC treatment arms.

CONCLUSIONS: The effects of collaborative care may vary according to patients’ baseline clinical complexity. Collaborative care appears to be associated with more favorable depression outcomes than enhanced usual care among participants with lower clinical complexity but not among those with higher clinical complexity.

PMID:42286436 | DOI:10.1111/add.70503

Gen Thorac Cardiovasc Surg. 2026 Jun 12. doi: 10.1007/s11748-026-02326-3. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine the surgical outcomes of surgical aortic valve replacement in the transcatheter aortic valve replacement era and propose a novel patient-specific prognostic model.

METHODS: We randomly divided 772 patients with aortic stenosis who underwent surgical aortic valve replacement in 2016-2021 into two cohorts (derivation, 515; validation, 257). In the derivation cohort, no data were missing for any patients for the candidate predictors including age, sex, body mass index, left ventricular ejection fraction, levels of albumin, hemoglobin, and serum creatinine, presence of chronic atrial fibrillation, and end-stage renal disease requiring hemodialysis. We developed possible scoring models using Cox proportional hazards regression with overall survival as the endpoint and calculated the cross-validated 5-year C-statistics to assess accuracy.

RESULTS: The mean patient age was 74.2 years, and 46.9% were female. Kaplan-Meier analysis revealed overall 1- and 5-year survival rates of 96.6 and 88.7%, respectively. The 5-year C-statistic of the derivation cohort was 0.785 (95% confidence interval: 0.716-0.853), while the estimated 1-, 3-, and 5-year C-statistics of the validation cohort were 0.885 (0.806-0.965), 0.888 (0.824-0.953), and 0.801 (0.702-0.901), respectively. Calibration plots revealed good agreement between predicted and actual 5-year survival (intraclass correlation coefficient = 0.955; 95% confidence interval: 0.827-0.989).

CONCLUSIONS: This novel survival prediction model after isolated surgical aortic valve replacement in the transcatheter aortic valve replacement era showed good survival prediction, and may guide the decision-making process for surgical aortic valve replacement versus transcatheter aortic valve replacement with lifetime management.

PMID:42286392 | DOI:10.1007/s11748-026-02326-3

Breast Cancer. 2026 Jun 12. doi: 10.1007/s12282-026-01881-0. Online ahead of print.

ABSTRACT

This annual report of the National Clinical Database-Breast Cancer Registry (NCD-BCR) by the Japanese Breast Cancer Society presents nationwide breast cancer statistics for patients registered in Japan in 2023. Among 107,372 patients with breast cancer at 1317 institutions, 99.3% were females with a median age of 62 years. The distribution of the clinical stages was as follows: stage 0 (15.5%); stage I (42.1%); stage II (31.1%); stage III (7.0%); and stage IV (2.1%). Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) positivity was observed in 78.9%, 70.0%, and 13.3% of patients, respectively. Among 102,717 patients without distant metastases, 41.2% underwent breast-conserving surgery, 76.5% underwent sentinel lymph node biopsy, and 6.0% underwent breast reconstruction. The distribution of radiotherapy was as follows: 75.2% received whole-breast irradiation, 15.7% chest-wall irradiation, and 20.7% regional irradiation. Among the 13,061 patients with pT1abN0M0 breast cancer, comprising 10,819 hormone receptor [HR]-positive/HER2-negative, 1479 HER2-positive and 763 HR-negative/HER2-negative individuals, 92.4% of HR-positive/HER2-negative patients received endocrine therapy, 46.9% of HER2-positive patients received chemotherapy and/or anti-HER2 therapy, and 31.2% of HR-negative/HER2-negative patients received chemotherapy. This annual report provides a nationwide overview of contemporary systemic therapy patterns in small breast cancer and highlights size‑dependent and subtype‑specific use of systemic therapy in Japan, reflecting a risk‑adapted treatment strategy.

PMID:42286387 | DOI:10.1007/s12282-026-01881-0

Breast Cancer. 2026 Jun 12. doi: 10.1007/s12282-026-01869-w. Online ahead of print.

ABSTRACT

BACKGROUND: Bevacizumab is an anti-angiogenic agent that inhibits tumor vascularization and thereby suppresses tumor growth. Tumor-infiltrating lymphocytes (TILs), particularly CD8-positive TILs, play a critical role in the antitumor immune response. However, little is known about the effect of bevacizumab-containing chemotherapy on CD8-positive TIL dynamics. This study aimed to evaluate changes in CD8-positive TILs before and after treatment in patients with advanced breast cancer receiving bevacizumab in combination with chemotherapy.

METHODS: Thirty patients with initially inoperable advanced breast cancer who responded to first-line bevacizumab-containing chemotherapy and subsequently became eligible for surgery were included. CD8-positive TILs were assessed by immunohistochemistry in biopsy samples obtained before treatment and in surgical specimens collected after treatment. Stromal CD8-positive TILs were classified as low, intermediate, or high, based on their proportion among total stromal TILs.

RESULTS: Of the 30 patients, 20 had luminal-like breast cancer and 10 had triple-negative breast cancer. Before treatment, CD8-positive TIL expression was low in 16 patients (64.0%), intermediate in 6 (24.0%), and high in 3 (12.0%). After treatment, 10 patients (33.3%) showed low expression, 11 (36.7%) had intermediate expression, and 9 (30.0%) had high expression, indicating an increase in CD8-positive TIL levels. The high pathological response (a pathological response grade of 2 or higher) rate was 36.7%, and patients with increased CD8-positive TILs tended to show higher pathological response and better overall survival, although these differences did not reach statistical significance. In contrast, the ypT stage was significantly lower in cases with high post-treatment CD8-positive TIL expression, suggesting that immune activation after bevacizumab may contribute to local tumor regression.

CONCLUSIONS: Bevacizumab-containing chemotherapy appears to enhance CD8-positive TIL infiltration in primary breast tumors, which may contribute to improved local tumor regression and better therapeutic outcomes.

PMID:42286385 | DOI:10.1007/s12282-026-01869-w

Eur Spine J. 2026 Jun 12. doi: 10.1007/s00586-026-10072-6. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to characterize biochemical and microenvironmental changes within the Disc Vertebra Complex (DVC) in non-specific low back pain (NSLBP) patients using non-fat-saturation Multi-slices CEST MRI. By performing intra-group comparisons, we assessed associations between disc degeneration and vertebral biochemical variations.

METHODS: Ninety-nine NSLBP patients (62 males, 37 females; median age 45) underwent lumbar spine MRI. Non-fat-saturation Multi-slices CEST imaging was used to assess fat fraction (FF), fat /water content and magnetization transfer contrast in vertebrates, and water content, glycosaminoglycan (GAG), amide proton transfer (APT), nuclear overhauser enhancement (NOE) and magnetization transfer contrast in discs. Metabolic and microenvironmental changes across vertebrae (L2-S1) and intervertebral discs (L2/3-L5/S1) were analyzed. Statistical comparisons were conducted across disc grades, weight categories, and disc abnormalities.

RESULTS: Significant biochemical variations were observed across vertebral levels, with decreasing water content and increasing FF from L2 to S1. The pH-sensitive markers (APT) showed caudal trends, indicating relative changes in proton environment. Protruding discs and discs with high-intensity zones (HIZ) showed reduced pH and hydration, alongside altered macromolecular structures. Adjacent vertebrae of protruding discs exhibited decreased water content, indicative of early bone marrow edema.

CONCLUSIONS: Non-fat-saturation Multi-slices CEST MRI enables holistic profiling of the disc-vertebra complex (DVC) and detects localized, grade-dependent biochemical heterogeneity. Notably, differences emerged between vertebrae and discs with and without protrusion / HIZ, alongside grade-dependent variations.

PMID:42286353 | DOI:10.1007/s00586-026-10072-6