Nevin Manimala

J Neural Transm (Vienna). 2025 Aug 16. doi: 10.1007/s00702-025-02999-9. Online ahead of print.

ABSTRACT

Precision medicine driven by clinical biomarkers is the state-of-art management approach for Parkinson’s disease (PD). Whether pattern of striatal dopaminergic deficiency (demonstrated by single-photon emission CT (SPECT) scanning with ¹²³I-Ioflupane, DaTSCAN) could be a biomarker predicting levodopa requirement in early PD is not known. Participants with early PD (disease duration (DD) ≤ 5 years, Hoehn and Yahr (H&Y) ≤ 3) who underwent DaTSCAN as a part of clinical-diagnostic work up and were enrolled in the “Non-motor Longitudinal International Study” (UK National Institute for Health Research Clinical Research Network Number 10084) were included in this cross-sectional analysis. Specific DaTSCAN binding ratios were analyzed for each striatum, caudate nucleus and putamen and the z-scores were derived normalizing the images to age and gender-matched healthy controls from the European-Database-of-DaTSCAN-of-healthy-controls (ENC-DAT). Using linear regression analysis, we explored the impact of DaT-uptake z-scores for more severely affected putamen, caudate nucleus and striatum on the LEDD. Statistically significant predictors identified in the univariable analysis were included in the multivariable analysis with DD and H&Y as additional independent variables. 43 PwP (30% female; age: 61.91 ± 11.45years; DD: 2(0-5) years; H&Y: 2(1-3); LEDD: 424.27 ± 342.62 mg) were assessed 19.12 ± 13.11 months following the DaTSCAN. In a multivariable linear regression analysis, when adjusted for DD and H&Y, z-caudate nucleus (B=-134.073, 95% CI -262.715 – -5.431, p = 0.042) and z-striatum (B=-162.137, 95% CI -306.306 – -17.967, p = 0.028), were statistically significant predictors of LEDD, while z-putamen was not (p = 0.086). In early PD, striatal DaT-uptake z-scores may serve as biomarkers that could aid the LEDD estimation and guide treatment decisions towards personalized care.

PMID:40817940 | DOI:10.1007/s00702-025-02999-9

Neurosurg Rev. 2025 Aug 16;48(1):605. doi: 10.1007/s10143-025-03760-2.

ABSTRACT

Double anastomosis Superficial Temporal Artery-Middle Cerebral Artery (STA-MCA) bypass in Moyamoya disease (MMD) and cerebral atherosclerosis disease (CAD) remains underexplored. We aim to evaluate the clinical efficacy and vascular dynamics of double anastomosis STA-MCA bypass in each group, MMD and CAD. A systematic search was conducted in ScienceDirect, Embase, PubMed, and Cochrane databases until September 2024. Efficacy outcomes included stroke occurrences, patency, modified Rankin Scale (mRS), and complications. Vascular parameters included cerebral blood flow (CBF), cut flow index (CFI), MCA perfusion, and mean transit time (MTT). The meta-analysis included 15 studies with 417 patients (46.18 ± 4.69 years). At final follow-up, the MMD group showed lower total stroke (12 ± 7% vs. 20 ± 9%; p = 0.63), ischemic stroke (8 ± 5% vs. 18 ± 8%; p = 0.26), hemorrhagic stroke (4 ± 3% vs. 10 ± 7%; p = 0.49), and patency (85 ± 11% vs. 98 ± 8%; p = 0.10) compared to CAD group, without statistical difference. The MMD group exhibited reduced mRS (MD: -0.57; 95%CI: -0.95 to -0.19; p = 0.003), increased CBF (MD: 14.75; 95%CI: 2.32 to 27.19; p = 0.020), and increased MCA perfusion (MD: 9.28; 95%CI: 1.19 to 17.37; p = 0.025). CFI (1.30 ± 0.11 vs. 1.08 ± 0.13; p = 0.02) and MTT (4.49 ± 0.5 vs. 1.27 ± 0.27; p < 0.001) were significantly higher in the CAD group. Both 1D2R (MD: 27.59; 95%CI: 4.88 to 50.30; p = 0.017) and 2D2R (MD: 14.75; 95%CI: 2.32 to 27.19; p = 0.020) techniques exhibited increase in CBF. Additionally, double anastomosis showed a higher CFI compared to single anastomosis (MD: 0.25; 95%CI: 0.12-0.38; p < 0.001). Double anastomosis STA-MCA bypass demonstrated comparable stroke and patency rates between groups. MMD patients had significantly higher CFI and MTT values, with double anastomosis yielding superior CFI compared to single anastomosis.

PMID:40817938 | DOI:10.1007/s10143-025-03760-2

Diabetologia. 2025 Aug 16. doi: 10.1007/s00125-025-06517-0. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: There is no clear consensus regarding accurate risk stratification in early pregnancy for later developing gestational diabetes mellitus (GDM). Therefore, this study aims to evaluate the predictive performance of an OGTT and several biomarkers in the first trimester of pregnancy. Their association with insulin action, beta cell function and requirement for insulin were additionally assessed.

METHODS: In this prospective cohort study, we included 657 pregnant women in six Central European centres. Patient history and anthropometric data were obtained, a blinded 75 g OGTT was performed and biochemical markers were assessed at a median gestational age of 13.4 weeks (IQR 12.7-14.1). Another OGTT was performed in later pregnancy to identify women with GDM. A detailed investigation of glucose homeostasis was performed at both visits in a subgroup of women.

RESULTS: Eighty-three women (12.6%) developed GDM. Progression to GDM was fairly well predicted by glucose concentrations during the early OGTT in terms of areas under the receiver operating characteristic curves (OGTT glucose at fasting: 0.68; OGTT glucose at 60 min: 0.74; OGTT glucose at 120 min: 0.72). Some biomarkers showed significant but modest predictive accuracy. Early gestational OGTT glucose concentrations were further associated with impaired insulin sensitivity and beta cell dysfunction, as well as the requirement for insulin in later pregnancy.

CONCLUSIONS/INTERPRETATION: Although the accurate diagnosis of GDM before 24 weeks remains an ongoing discussion, dynamically assessed glucose concentrations during an early OGTT were closely associated with impaired glucose homeostasis and showed good predictive accuracy for later development of GDM as well as the requirement for insulin. These findings may be used to develop a protocol to distinguish between low- and high-risk mothers. Trial registration ClinicalTrials.gov NCT02035059.

PMID:40817933 | DOI:10.1007/s00125-025-06517-0

Clin Chem Lab Med. 2025 Aug 18. doi: 10.1515/cclm-2025-0763. Online ahead of print.

ABSTRACT

Laboratory data can be meaningful only when compared with reliable reference data; therefore, the estimation of reliable reference data is just as important as the accurate measurement of measurands in patient samples. Since analyte concentrations in the human body are influenced by both random variations (such as biological fluctuations) and systematic variations (such as physiological rhythms and age-related changes), the conventional model for estimating reference data – based solely on the statistical distribution of single-sample measurements from reference individuals – may not provide sufficiently reliable information for interpreting patient results. Therefore, a paradigm shift from relying solely on single-sample measurement distributions to incorporating metabolic changes observed in the human body when estimating reference intervals may enhance the clinical value of laboratory data for an effective clinical decision making and patient care. This opinion paper aims to summarize how to facilitate this transition and to identify the most suitable model for estimating reference intervals that reflect underlying metabolic dynamics.

PMID:40817855 | DOI:10.1515/cclm-2025-0763

Anim Genet. 2025 Aug;56(4):e70037. doi: 10.1111/age.70037.

ABSTRACT

With advancing genomic technologies, single-nucleotide polymorphism (SNP) arrays and whole genome sequencing (WGS) have become essential tools in equine genetic research. In this study, we assessed the concordance in SNP calls and trait-mapping efficacy by comparing data of 21 horses both genotyped on the Equine 670 K SNP array and sequenced at either ~12× or ~30× depth. Our analysis revealed that higher sequencing depths were significantly associated with fewer discordant calls between platforms. Additionally, we investigated the most frequent no-call and discordant positions and identified positions that were indels or multiallelic in the WGS. To assess the effectiveness of the 670 K SNP array vs. WGS in trait association studies, we mapped the chestnut coat color. Both technologies showed a clear peak at the expected locus, although neither association had loci reaching Bonferroni-corrected statistical significance, which was not statistically possible in this small group of horses. The findings of this study provide valuable insights for making informed decisions when selecting between SNP arrays and WGS at varying sequencing depths for equine genomic research applications.

PMID:40817846 | DOI:10.1111/age.70037

J Clin Endocrinol Metab. 2025 Aug 16:dgaf461. doi: 10.1210/clinem/dgaf461. Online ahead of print.

ABSTRACT

OBJECTIVE: To study bone turnover markers (BTM) and sex steroids in relation to Trabecular Bone Score (TBS) in men.

MATERIAL AND METHODS: Longitudinal, population-based study in 465 healthy men, aged 25-45 years at baseline. Lumbar spine TBS was calculated with TBS iNsight® version 4 (v19.4.1, core module, Medimaps, Pessac, France), which adjusts for soft tissue thickness correction via DXA measurements. Sex hormone binding globulin (SHBG), C-terminal telopeptide and pro collagen type 1 N-terminal propeptide were measured using immunoassays. Total testosterone (T) and estradiol (E2) were determined by liquid chromatography-tandem mass spectrometry, free T and free E2 calculated. Statistical analyses were conducted via linear mixed-effects modelling.

RESULTS: At baseline, TBS was positively associated with free testosterone (p=0.01), free estradiol and total estradiol (both p<0.001), but not with total testosterone nor with BTM. Over a follow-up of 12.5 years, TBS declined by 1.43% (p<0.001). Higher baseline BMI and trunk fat were predictive of greater decreases in TBS (p=0.01 and p=0.02). Baseline levels of sex steroids and BTM nor changes therein were associated with changes in TBS.

CONCLUSIONS: TBS already decreases in young and middle-aged healthy men, corroborating earlier studies showing early decrease of trabecular bone volume and changes in trabecular microarchitecture. Although we identified some potentially contributing determinants, the underlying mechanisms of changes in TBS and trabecular bone in young men are yet to be fully elucidated.

PMID:40817832 | DOI:10.1210/clinem/dgaf461

J Vet Diagn Invest. 2025 Aug 16:10406387251357233. doi: 10.1177/10406387251357233. Online ahead of print.

ABSTRACT

Congestive heart failure (CHF) in feedyard cattle is of increasing concern among producers and can be difficult to diagnose definitively postmortem. In a cross-sectional observational study, we evaluated gross pathology findings, various heart measurements, and subjective heart scores (1-5 scale: 1 = normal, 5 = severely remodeled) to identify heart disease postmortem. In postmortem examinations of 346 feedyard deaths, we classified 106 (30.6%) cases as cardiac enlargement or misshapen ventricle (CEMV) when there was an abnormal heart shape or dilated ventricle(s), and no signs of infectious heart disease. CHF was defined as a CEMV case with chronic passive congestion of the liver (i.e., nutmeg liver) and ≥2 of the following lesions: serous or serosanguineous pleural, pericardial, or peritoneal effusion. Eleven of the 346 autopsied cattle were classified as having CHF. Descriptive statistics and multivariate models were used to identify statistical associations between objective heart measurements or subjective heart scores and the prevalence of CEMV or CHF. CEMV cases had significantly increased heart widths, thinner left ventricular free walls, and expanded right ventricular lumen areas (p <0.05). The CHF model did not converge because we had too few cases to be able to evaluate associations between CHF and variables of interest.

PMID:40817806 | DOI:10.1177/10406387251357233

Genet Med. 2025 Aug 13:101554. doi: 10.1016/j.gim.2025.101554. Online ahead of print.

ABSTRACT

PURPOSE: Through our implementation study providing rapid genomic sequencing (rGS) in safety-net Neonatal Intensive Care Units (NICUs), we investigated the feasibility and perceived usefulness of customized “Clinical Interpretive Reports” (CIRs) to help neonatal providers with interpreting, disclosing, and managing care based on rGS results.

METHODS: Enrolled infants received rGS through a clinically accredited vendor. We developed five CIR types to provide customized interpretation of rGS results and link results to clinical management considerations, research opportunities, and resources. We developed workflows to triage, create, and deliver CIRs within 3 business days. Providers received the vendor reports and CIRs, disclosed results, and completed post-disclosure surveys. We analyzed summary statistics for the first 100 cases.

RESULTS: We delivered 97/100 CIRs (97%) within our goal timeframe (average 1.3 days) and provided clinical management recommendations in 40/100 (40%). Neonatal providers completed the post-disclosure surveys for 86/100 disclosures (86%). Most reported using the CIR prior to disclosure (80/86, 93%) and finding it helpful at providing useful information beyond the vendor report (79/80, 99%).

CONCLUSIONS: It is feasible and useful to develop customized rGS reports to assist non-genetics providers in safety-net NICU settings. Similar approaches may hold promise for equitably advancing genomic care in other non-NICU settings.

PMID:40817795 | DOI:10.1016/j.gim.2025.101554

Stat Med. 2025 Aug;44(18-19):e70232. doi: 10.1002/sim.70232.

ABSTRACT

In this article, we consider the semiparametric transformation models with a shared frailty variable for the rate function of recurrent events, where a shared frailty model is imposed to enable a correlation between the recurrent event process and the censoring time. Unlike the commonly used shared-frailty proportional rate models, our models allow for the rate functions associated with any two sets of covariate values not to be proportional over time. The proposed estimating approaches are inspired by Wang and Huang, who decompose the rate function into shape and size components. We start with the inverse-rate weighting approach and subsequently introduce a novel generalized method of moments framework to improve estimation efficiency by combining the estimating procedures derived from the shape and size components, respectively. The proposed methods are robust because they do not require the assumption of a Poisson process for the recurrent events or distributional assumptions for the frailty and censoring times. The large sample properties of the proposed methods are established, and the finite sample properties are examined through the simulation studies. The proposed methods are applied to a real data set.

PMID:40817780 | DOI:10.1002/sim.70232

Stat Med. 2025 Aug;44(18-19):e70231. doi: 10.1002/sim.70231.

ABSTRACT

A functional multistate model is presented, which accommodates Markov processes governing disease transition in a finite set of states. Importantly, we consider a setting where the set of predictors contains a high-dimensional image with the goal of quantifying the association between the image and the transition of disease states. In the motivating application of breast cancer, women start from normal breast tissue, go through benign lesions, and then to the onset of DCIS/invasive cancer. As in the real data application, we consider the setting in which the individuals are observed intermittently and the transition times are interval censored. A score test is developed to test the nullity of the coefficient function for the image predictor at different transitions between states. The asymptotic distribution of the score statistic is provided. An application involving progression to the development of breast cancer with mammogram image data provides illustration. Our results demonstrate an important association between the mammogram image and the probability of transition in breast cancer.

PMID:40817779 | DOI:10.1002/sim.70231