Tag: pubmed

J Chem Theory Comput. 2026 Apr 20. doi: 10.1021/acs.jctc.6c00418. Online ahead of print.

ABSTRACT

While recent advances in AI have transformed protein structure prediction, protein function is also strongly influenced by the thermodynamic and kinetic features encoded in its underlying free-energy surface. Here, we propose a framework to rationally reshape this landscape in order to control conformational transition rates, built on the Collective Variables for Free Energy Surface Tailoring (CV-FEST) framework, and validate it on point mutations of the miniprotein Chignolin. The framework relies on Harmonic Linear Discriminant Analysis (HLDA)-based collective variables (CVs) constructed from short molecular dynamics trajectories confined to metastable basins, requiring only limited sampling within each basin. Notably, the HLDA CV derived solely from the wild-type system already provides residue-level scores that predict whether mutations at specific positions are likely to accelerate or slow unfolding transitions. Furthermore, we find that the leading HLDA eigenvalue associated with the derived CV, a quantitative measure of the one-dimensional statistical separation between folded and unfolded ensembles, is significantly correlated with transition rates across mutations. Together, these results suggest that kinetic effects of point mutations can be inferred from minimal local sampling, providing a practical route for guiding the engineering of transition rates without exhaustive simulations or large training data sets.

PMID:42007551 | DOI:10.1021/acs.jctc.6c00418

Clin Oral Implants Res. 2026 Apr 20. doi: 10.1111/clr.70130. Online ahead of print.

ABSTRACT

OBJECTIVES: This laboratory study investigated the effect of two different retentive heights of Ti-base abutments (3.5 and 5.5 mm) and crown heights (13 and 16 mm) on the load at failure and survival of monolithic zirconia implant-supported crowns replacing a maxillary central incisor.

MATERIALS AND METHOD: Forty implant-supported crowns were divided into four groups (n = 10 each): short crown/long abutment (SCLA), short crown/short abutment (SCSA), long crown/long abutment (LCLA), and long crown/short abutment (LCSA). Specimens underwent thermal cycling and incremental mechanical cyclic loading starting at 450 N increasing by 50 N until failure. Load and cycles at failure, Weibull analysis, mode of failure, and fractographic assessments were performed.

RESULTS: Mean load at failure was highest for the SCSA group (536.9 N ± 78.4 N), then SCLA (493.4 ± 53.2 N) and LCLA (491.3 ± 40.7 N), and lowest for the LCSA group (453.7 N ± 2.8 N). The differences were statistically significant (p = 0.035). Cycles at failure showed significant differences among groups (p < 0.001), with SCSA demonstrating the greatest cycles at failure (72,492 ± 44,551 cycles), then SCLA (43,630 ± 27,579 cycles) and LCLA (37,706 ± 18,826 cycles), and LCSA the lowest (8399 ± 7308 cycles). Short crowns showed abutment/screw fractures, while longer crowns had more crown fractures.

CONCLUSION: Crown height significantly influenced load at failure and survival, with shorter crowns performing better. The retentive height of the Ti-base abutment had less impact; however, shorter abutments provided better mechanical performance when paired with shorter crowns, suggesting careful consideration for anterior restorations.

PMID:42007538 | DOI:10.1111/clr.70130

J Comput Chem. 2026 Apr 30;47(11):e70380. doi: 10.1002/jcc.70380.

ABSTRACT

In molecular research, comprehending the microscopic source of the macroscopic characteristics of polar aprotic solvents continues to be a significant difficulty. In order to bridge the gap between cluster-scale interactions and liquid acetone properties, we present a thorough quantum-chemical and statistical modeling of neutral acetone clusters in this work. The ABCluster algorithm was used to thoroughly explore the potential energy surface. High-level density functional theory calculations at the MN12SX-D3/def2-TZVP level were then performed, benchmarked against DLPNO-CCSD(T)/CBS reference energies. A thorough Quantum Theory of Atoms in Molecules (QTAIM) analysis of the nature and hierarchy of intermolecular interactions revealed a cooperative network dominated by dipole-dipole O⋯C and O⋯O interactions, supplemented by numerous weak C-H⋯O, H⋯C, and H⋯H dispersive contacts. The application of the QCE theory predicts a distribution dominated by trimers at low temperatures (T< 200 K), leading to a predominance of monomers above 260-280 K, reflecting the subtle equilibrium between electrostatic stabilization and entropic effects. The model reproduces experimental thermodynamic properties, such as the thermal capacity (Cp) between 200 and 375 K and infrared spectra at 300 K, with the calculated band of elongation C=O (1710 cm^-1) being just 5 cm^-1 from the experimental value (1715 cm^-1). The thermodynamic properties and infrared spectrum of liquid acetone predicted by QCE show excellent agreement with experimental data, thus validating the integrated DFT-QTAIM-QCE approach. This work provides the first complete QCE characterization of pure liquid acetone, demonstrating that its macroscopic properties emerge from a dynamic equilibrium of small, weakly-bound clusters rather than extended hydrogen-bonded networks, and establishes a validated computational framework for predicting liquid-phase properties from ab initio cluster data.

PMID:42007531 | DOI:10.1002/jcc.70380

Phys Occup Ther Pediatr. 2026 Apr 20:1-14. doi: 10.1080/01942638.2026.2660349. Online ahead of print.

ABSTRACT

AIMS: This study aims to evaluate the immediate clinical effect of kinesiotaping in treatment of children with Legg-Calvé-Perthes Disease (LCPD).

METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted with 30 participants, ages 6 to 15, who were randomly assigned to either the kinesiotaping or sham taping group. All participants were assessed before and 30 min after the intervention. Primary outcomes included activity-related hip pain measured by a visual analogue scale, pain-limited goniometric range of motion of the affected hip, and maximal isometric force of gluteus medius muscle. Secondary outcomes encompassed functional performance (10-meter walking test and 10-step climbing test durations) and balance (one-leg stance and tandem walk test durations).

RESULTS: Both groups demonstrated significant within-group improvements in activity-related pain, pain-limited range of motion, maximal isometric force, tandem walking test, and 10-meter walking performance (p < 0.05). Improvement in the 10-step climbing test was observed only in the kinesiotaping group. However, no statistically significant between-group differences were detected for any outcome (p > 0.05).

CONCLUSION: Kinesiotaping did not demonstrate superiority over sham taping in children with LCPD. The observed improvements are therefore likely attributable to placebo or nonspecific contextual effects rather than to the taping itself.

PMID:42007529 | DOI:10.1080/01942638.2026.2660349

Front Endocrinol (Lausanne). 2026 Apr 2;16:1639188. doi: 10.3389/fendo.2025.1639188. eCollection 2025.

ABSTRACT

OBJECTIVE: To compare the cycle of initial twin pregnancy with vanishing twin syndrome (VTS), the cycle of initial twin pregnancy after surgical reduction, and the live birth outcome of initial singleton pregnancy. To provide clinical evidence for confirming that vanishing twin syndrome (VTS) and surgical reduction may affect obstetric and perinatal outcomes.

METHODS: A retrospective study was conducted on patients diagnosed with MFPR and VTS at the Reproductive Medicine Hospital of the First Hospital of Lanzhou University from January 2017 to December 2021. A total of 1,796 singleton patients were ultimately included, comprising 271 patients with naturally reduced twin pregnancies, 84 patients with surgically reduced twin pregnancies, and 1,441 patients with singleton pregnancies after IVF/ICSI-assisted conception. A comparison was made on the clinical characteristics and pregnancy outcomes of the three groups.

RESULTS: The rates of preterm birth and low birth weight in the MFPR group were significantly higher than those in the VTS group and the control group (P < 0.05). The miscarriage rate in the MFPR group was significantly higher than that in the VTS group (P < 0.05), but there was no statistically significant difference compared with the control group (P > 0.05). In contrast, the VTS group showed comparable gestational age and birth weight to the control group, with an even lower miscarriage rate. Within the MFPR cohort, Monochorionic diamniotic twin pregnancy (MDT) pregnancies had a higher risk of miscarriage than Dichorionic diamniotic twin pregnancy (DDT) pregnancies (P<0.05). ROC analysis indicated that serum β-hCG levels on day 14 post-transfer had value in distinguishing VTS from initial singletons (AUC = 0.75), with a cutoff of 837 mIU/ml.

CONCLUSIONS: The VTS population may have better pregnancy outcomes than the MFPR population and the β-hCG level has certain clinical application value. At the same time, the MFPR in DDT pregnancy is more challenging than that in MDT pregnancy.

PMID:42007464 | PMC:PMC13082931 | DOI:10.3389/fendo.2025.1639188

Vet Evid. 2023 Sep 15;8(3):vetevid-8-3-666. doi: 10.18849/ve.v8i3.666. eCollection 2023 Jul-Sep.

ABSTRACT

PICO QUESTION: In symptomatic cats with feline immunodeficiency virus (FIV), does high-dose subcutaneous recombinant feline interferon-omega (rFeIFN-ω) administration lead to reduced clinical signs compared to cats who were not administered rFeIFN-ω?

CATEGORY OF RESEARCH: Treatment.

NUMBER AND TYPE OF STUDY DESIGNS REVIEWED: Three studies were critically reviewed, including one randomised controlled trial, one non-randomised controlled trial, and one uncontrolled clinical trial.

STRENGTH OF EVIDENCE: Weak.

OUTCOMES REPORTED: Each of the studies reported that rFeIFN-ω administration significantly reduced clinical signs in FIV infected cats. However, all three papers have limitations in their study design and statistical analysis which lower the strength of the evidence they provide.

CONCLUSION: There is only weak evidence demonstrating that rFeIFN-ω administration leads to reduced clinical signs in FIV positive cats. Currently, there is a lack of well-designed, double-blinded, randomised, placebo-controlled clinical trials which have an adequate sample size and specifically focus on FIV positive cats. As a result, more robust evidence is needed to prove the definitive therapeutic benefit of rFeIFN-ω in symptomatic FIV patients. Treatment with rFeIFN-ω may still be considered by clinicians for cats with clinical signs potentially associated with retroviral infection, such as oral lesions and stomatitis, particularly if they are not responding well to supportive therapy alone.

PMID:42007441 | PMC:PMC13011114 | DOI:10.18849/ve.v8i3.666

JSES Int. 2026 Feb 28;10(3):101676. doi: 10.1016/j.jseint.2026.101676. eCollection 2026 May.

ABSTRACT

BACKGROUND: Imaging in children with capitellar osteochondritis dissecans (COCD) is crucial for surgical decision-making but remains challenging. Novel photon-counting computed tomography (PCCT) technology enables superior resolution while reducing radiation dose. This study aims to describe interrater agreement (IRA) for COCD characteristics assessed with PCCT and to make a comparison with conventional CT.

METHODS: At a tertiary referral hospital, anonymized PCCT and conventional CT scans of COCD lesions were assessed systematically and independently by 2 experienced clinicians and 2 musculoskeletal radiologists, excluding postoperative scans. The intraclass correlation coefficient (ICC) with 95% confidence intervals was used to describe IRA among all raters.

RESULTS: In the PCCT group (n = 29), ICCs for loose body count, lesion size in the sagittal plane, presence of an empty defect, and presence of an osseous bridge were 0.75 (95% CI: 0.61-0.86), 0.68 (0.51-0.81), 0.64 (0.47-0.78), and 0.60 (0.43-0.76), respectively. ICCs of physeal status, lateral wall involvement, fragmentation, depth, and tilting had a lower bound of the 95% confidence interval below 0.4. In the conventional CT group (n = 12), ICCs for loose body count and osseous bridging were statistically significantly lower than in the PCCT group after adjustment for multiple testing (P = .009 and P = .025, respectively).

CONCLUSION: PCCT assessment of COCD demonstrates at least substantial IRA for loose body count and at least moderate IRA for lesion size and the presence of an empty defect or bony bridge. Moreover, PCCT may enable higher IRA than conventional CT.

PMID:42007424 | PMC:PMC13091507 | DOI:10.1016/j.jseint.2026.101676

JSES Int. 2026 Feb 11;10(3):101668. doi: 10.1016/j.jseint.2026.101668. eCollection 2026 May.

ABSTRACT

BACKGROUND: Proximal humerus fractures are a common challenge in patients with initial treatment ranging from nonoperative management, to open reduction and internal fixation, to arthroplasty. Initial treatment failure is not uncommon, and revision to reverse total shoulder arthroplasty (rTSA) has emerged as a viable salvage option, though long-term outcomes in these patients are variable and remain underreported. This study aimed to evaluate long-term outcomes and failure rates of rTSA after failed initial proximal humerus management (nonoperative and operative). We hypothesized that rTSA for sequelae of fracture after failed treatment would lead to durable and beneficial outcome as well as a low failure rate.

METHODS: After institutional review board approval, a retrospective review was conducted of patients who underwent rTSA for sequelae of fracture for failed treatment between 2007 and 2020, with a minimum of 24 months’ follow-up. Outcomes included American Shoulder and Elbow Surgeons (ASES), Quick Disabilities of the Arm, Shoulder, and Hand, Single Assessment Numeric Evaluation, 12-Item Short-Form Health Survey (Physical Component Summary/Mental Component Summary), pain scores, range of motion and complication/failure rates. Statistical analyses were performed using paired tests, with significance set at P < .05.

RESULTS: Sixteen shoulders (84.2%) of 15 patients were included in the final analysis. The mean follow-up was 100.8 ± 48.1 months. Significant improvements were observed in ASES (from 45.8 to 69.6; P = .002), Quick Disabilities of the Arm, Shoulder, and Hand (from 47.9 to 29.5; P = .002), daily pain visual analog scale (from 5 to 1; P = .003), and maximum pain visual analog scale (from 8 to 5; P = .01). ASES patient acceptable symptom state and minimal clinically important difference thresholds were achieved by 62.5% and 43.8% of patients, respectively. Also, patient satisfaction was high (median 8/10). External rotation (20.7 ± 18.7 vs. 34.6 ± 19.2; P = .048) and forward flexion (66.3 ± 35.7 vs. 125.7 ± 33.2; P < .001) significantly improved from pre-operatively to post-operatively. The overall complication and failure rates were low (1 case each; 6.3% each).

CONCLUSION: rTSA performed for sequelae of fracture to failed initial treatment (nonoperative or operative) of proximal humerus fractures was associated with substantial and durable improvement in pain and patient-reported function as well as restoration of range of motion, with a low rate of subsequent construct revision in this cohort. These findings support rTSA for sequelae of fracture as a suitable treatment option when initial management fails in this patient population.

PMID:42007418 | PMC:PMC13091508 | DOI:10.1016/j.jseint.2026.101668

Stat Comput. 2026;36(3):120. doi: 10.1007/s11222-026-10875-z. Epub 2026 Apr 17.

ABSTRACT

Efficient Bayesian model selection relies on the model evidence or marginal likelihood, whose computation often requires evaluating an intractable integral. The harmonic mean estimator (HME) has long been a standard method of approximating the evidence. While computationally simple, the version introduced by Newton and Raftery (1994) potentially suffers from infinite variance. To overcome this issue, Gelfand and Dey (1994) defined a standardized representation of the estimator based on an instrumental function and Robert and Wraith (2009) later proposed to use higher posterior density (HPD) indicators as instrumental functions. Following this approach, a practical method is proposed, based on an elliptical covering of the HPD region with non-overlapping ellipsoids. The resulting estimator, called the Elliptical Covering Marginal Likelihood Estimator (ECMLE), not only eliminates the infinite-variance issue of the original HME and allows exact volume computations, but is also able to be used in multimodal settings. Through several examples, we illustrate that ECMLE outperforms other recent methods such as THAMES and its improved version (Metodiev et al. 2025). Moreover, ECMLE demonstrates lower variance-a key challenge that subsequent HME variants have sought to address-and provides more stable evidence approximations, even in challenging settings.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11222-026-10875-z.

PMID:42007416 | PMC:PMC13090188 | DOI:10.1007/s11222-026-10875-z

Adv Alzheimer Dis. 2025 Jun;14(2):23-37. doi: 10.4236/aad.2025.142002. Epub 2025 Jun 30.

ABSTRACT

BACKGROUND: Alzheimer’s disease (AD) disproportionately affects Black/African American (B/AA) older adults, yet this group remains underrepresented in research. Traditional neuropsychological assessments, often developed on predominantly White populations, may not be reliable for B/AA individuals. The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) have been shown to effectively differentiate individuals with amnestic mild cognitive impairment (aMCI) from cognitively unimpaired (CU) individuals. This study examines the relationship between LASSI-L performance and plasma p-tau₂₁₇ levels to explore early detection methods for AD in B/AA populations.

METHODS: Fifty-six older adults received clinical and cognitive evaluations and were deemed cognitively unimpaired (CU) and p-tau₂₁₇ negative (n = 35) or met criteria for amnestic mild cognitive impairment (aMCI) and p-tau₂₁₇ positive (n = 21). All participants were administered the LASSI-L to compare groups, but it was not used for group allocation to avoid circularity.

RESULTS: After adjusting for age and MMSE score, the aMCI p-tau₂₁₇+ group performed significantly worse than the CU p-tau₂₁₇– group on both free recall on List B (Free B1 Recall) and frPSI (correct responses on Cued B2). These differences remained statistically significant after covariate adjustment (p < 0.001). In addition, four other outcomes remained statistically significant following covariate adjustment: the aMCI p-tau₂₁₇+ group exhibited a higher percentage of intrusion errors (PIE) on both Cued B1 and Cued B2, along with poorer performance on maximal learning ability (Cued A2) and PSI (correct responses on Cued B1). However, after applying the Bonferroni correction, only PIE on Cued B2 remained statistically significant among these measures. Notably, performance on LASSI-L Free B1 Recall and PIE for List Cued B2 were significant predictors distinguishing aMCI p-tau₂₁₇+ from CU p-tau₂₁₇– groups, with high sensitivity (80%) and specificity (91.7%). ROC analysis of these predictors yielded an area under the curve of 0.872 (SE = 0.055; p < 0.001), with a 95% confidence interval ranging from 0.765 to 0.979.

CONCLUSION: The study highlights the utility of the LASSI-L in conjunction with plasma biomarkers, particularly p-tau₂₁₇, for early AD detection in B/AA older adults. The LASSI-L demonstrated strong sensitivity to cognitive impairment, effectively differentiating between CU and aMCI groups based on plasma p-tau₂₁₇ levels. These findings suggest that combining cognitive assessments with plasma biomarkers can enhance early diagnosis and improve timely interventions, addressing health disparities in AD diagnosis and care.

PMID:42007415 | PMC:PMC13089353 | DOI:10.4236/aad.2025.142002