Tag: nevin manimala

Clin Transl Sci. 2025 Oct;18(10):e70365. doi: 10.1111/cts.70365.

ABSTRACT

Rare diseases affect a small population of patients, resulting in low incentives for developing orphan drug products (ODPs). The United States Congress passed the Orphan Drug Act of 1983 to incentivize pharmaceutical manufacturers to develop drugs to treat rare diseases. However, ODPs generally have higher treatment costs than non-ODP treatments. Developing generic ODPs can benefit patients by increasing market competition and providing alternate treatment options. This research aims to identify factors influencing the first submission of abbreviated new drug applications (ANDAs) for generic orphan drugs. Data were collected from the U.S. Food and Drug Administration (FDA) databases (including but not limited to the FDA Orphan Drug Designations and Approvals database, Orange Book, and the internal drug product complexity designation) and the IQVIA sales database to inform the drug product information, regulatory factors, and pharmacoeconomic factors. The Random Survival Forest (RSF) machine learning method was employed to conduct the analysis for New Chemical Entities (NCEs) and non-NCEs. The modeling analysis was adequately assessed through both internal and external validations. For NCEs and non-NCEs, the RSF was able to predict ANDA submission with a repeated cross-validation C-index of 0.675 ± 0.0261 (C-index of full training dataset: 0.915) and 0.754 ± 0.0441 (C-index of full training dataset: 0.838), respectively. The variables with the highest importance in the RSF model to predict ANDA submission of NCE ODPs were sales data, while for non-NCEs, regulatory data was the most important (i.e., availability of product-specific guidances (PSGs)). As more data becomes available in the future, the RSF methodology will likely be able to predict ANDA submissions of ODPs more effectively. The model-informed results may be utilized in future intervention strategies to promote ANDA submissions for orphan drugs and to increase the availability of generic ODPs.

PMID:41046470 | DOI:10.1111/cts.70365

Clin Transl Sci. 2025 Oct;18(10):e70372. doi: 10.1111/cts.70372.

ABSTRACT

Although extensive research has linked education to the Stroop effect, the neural mechanisms by which higher education influences Stroop performance in non-demented older adults remain unclear. This study investigated this relationship in 126 older adults from Qingdao, stratified into higher education (> 12 years) and non-higher education (≤ 12 years) groups. Demographic data and Stroop performance were collected using a 50-item Stroop Color-Word Test (SCWT), yielding measures of completion time, correct responses, score-time ratio (efficiency), and time interference score (TI). Resting-state fMRI (rs-fMRI) was performed, and neural activity was assessed via amplitude of low-frequency fluctuations (ALFF) to identify regions of interest (ROIs). Multivariable regression models examined associations between education and Stroop outcomes, followed by correlation analyses between ROIs and performance. Bootstrap mediation analysis (5000 resamples) tested whether ROIs mediated the education-Stroop relationship. Results showed that higher education was significantly associated with better Stroop performance-shorter completion time, higher efficiency, and lower TI-after full adjustment (all p < 0.05). Rs-fMRI revealed greater ALFF in the right frontal eye field (FEF), right dorsolateral prefrontal cortex (DLPFC), and left dorsal anterior cingulate cortex (dACC) in the higher education group. These regions correlated negatively with completion time and TI, and positively with efficiency. Mediation analyses confirmed that right FEF, right DLPFC, and the combined ROIs significantly mediated the effects of higher education on Stroop performance. In conclusion, higher education may enhance Stroop performance in non-demented older adults by modulating resting-state neural activity in key cognitive control regions.

PMID:41046460 | DOI:10.1111/cts.70372

Phys Rev Lett. 2025 Sep 19;135(12):126503. doi: 10.1103/tp8x-dscx.

ABSTRACT

The quantum loop and dimer models are archetypal correlated systems with local constraints. With natural foundations in statistical mechanics, they are of direct relevance to various important physical concepts and systems, such as topological order, lattice gauge theories, geometric frustrations, or more recently Rydberg array quantum simulators. However, how the thermal fluctuations interact with constraints has not been explored in the important class of nonbipartite geometries. Here we study, via unbiased quantum Monte Carlo simulations and field theoretical analysis, the finite-temperature phase diagram of the quantum loop model on the triangular lattice. We discover that the recently identified, “hidden” vison plaquette (VP) quantum crystal [X. Ran et al., Hidden orders and phase transitions for the fully packed quantum loop model on the triangular lattice, Commun. Phys. 7, 207 (2024)CMPYEL0868-316610.1038/s42005-024-01680-z] experiences a finite-temperature continuous transition, which smoothly connects to the (2+1)d Cubic* quantum critical point separating the VP and Z_{2} quantum spin liquid phases. This finite-temperature phase transition acquires a unique property of “remnants of fractionalization” at finite temperature, in that, both the cubic order parameter-the plaquette loop resonance-and its constituent-the vison field-exhibit independent criticality signatures. This phase transition is connected to a three-state Potts transition between the lattice nematic phase and the high-temperature disordered phase. We discuss the relevance of our results for current experiments on quantum simulation platforms.

PMID:41046441 | DOI:10.1103/tp8x-dscx

Phys Rev Lett. 2025 Sep 19;135(12):125201. doi: 10.1103/l6qw-8c1h.

ABSTRACT

Recently, solar gamma rays produced by cosmic rays interacting with the solar atmosphere have been detected in the GeV to TeV energy range, revealing that cosmic rays are significantly affected by magnetic fields in the solar atmosphere. However, much of the observations remain unexplained by existing physical models. Using a semianalytic model, we demonstrate that magnetic fields at and below the photosphere with a large horizontal component could account for the approximately 1 TeV solar gamma rays observed by HAWC. This suggests that high-energy solar gamma rays could serve as a novel probe for magnetic fields beneath the photosphere, which in the future could help improve the understanding of solar magnetism, the key driver of space weather.

PMID:41046434 | DOI:10.1103/l6qw-8c1h

Phys Rev Lett. 2025 Sep 19;135(12):126605. doi: 10.1103/x4w5-h3bb.

ABSTRACT

Existing quantum Hall interferometers measure twice the braiding phase, e^{i2θ}, of Abelian anyons, i.e., the phase accrued when one quasiparticle encircles another clockwise. We propose a modified Fabry-Pérot or Mach-Zehnder interferometer that can measure e^{iθ}.

PMID:41046427 | DOI:10.1103/x4w5-h3bb

Phys Rev Lett. 2025 Sep 19;135(12):120603. doi: 10.1103/nh49-52y2.

ABSTRACT

We identify regimes where postselection can be used scalably in quantum error correction (QEC) to improve performance. We use statistical mechanical models to analytically quantify the performance and thresholds of postselected QEC, with a focus on the surface code. Based on the nonequilibrium magnetization of these models, we identify a simple heuristic technique for postselection that determines whether to abort without requiring a decoder. Along with performance gains, this heuristic allows us to derive analytic expressions for postselected conditional logical thresholds and abort thresholds of surface codes. We find that such postselected QEC is characterized by four distinct thermodynamic phases and detail the implications of this phase space for practical, scalable quantum computation.

PMID:41046413 | DOI:10.1103/nh49-52y2

Ear Nose Throat J. 2025 Oct 5:1455613251378726. doi: 10.1177/01455613251378726. Online ahead of print.

ABSTRACT

BACKGROUND: Laryngopharyngeal reflux (LPR), allergic rhinitis (AR), and asthma are common airway disorders that often coexist, suggesting shared inflammatory mechanisms. LPR involves gastric reflux into the laryngopharynx, while AR and asthma are linked by the “united airway” hypothesis. Evidence indicates LPR may contribute to AR and asthma exacerbation, yet their interactions remain unclear. Understanding their interaction may enhance clinical outcomes.

OBJECTIVE: This systematic review aimed to evaluate the associations between LPR, AR, and asthma by analyzing studies that examined these conditions in various patient populations.

METHODOLOGY: A comprehensive search of electronic databases, including PubMed, Scopus, and Google Scholar, was conducted for studies published up until 2024. Eligible studies were selected based on predefined inclusion criteria, and data on the prevalence, diagnostic methods, and associations between LPR, AR, and asthma were extracted. This systematic review was conducted and registered in PROSPERO (CRD42024588367). Statistical analysis was performed to determine the strength of the associations between these conditions.

RESULTS: The review identified significant associations between LPR and both AR and asthma. Multiple studies confirmed a positive correlation between LPR and AR, with worse AR symptoms observed in patients with more severe LPR. Additionally, a strong association between LPR and asthma was observed, particularly in patients with poorly-controlled asthma. The analysis also revealed a robust relationship between AR and asthma, consistent with the “united airway” hypothesis, which posits that the upper and lower airways share common inflammatory pathways. These findings suggest that the coexistence of these conditions may exacerbate symptoms and complicate management.

CONCLUSION: This systematic review highlights the significant associations between LPR, AR, and asthma, emphasizing the importance of recognizing and addressing these comorbidities in clinical practice. The findings suggest that managing 1 condition may have a beneficial effect on the others, supporting a multidisciplinary approach to diagnosis and treatment.

PMID:41046361 | DOI:10.1177/01455613251378726

J Sex Med. 2025 Oct 5;22(10):1750-1756. doi: 10.1093/jsxmed/qdaf182.

ABSTRACT

BACKGROUND: Erectile dysfunction (ED) is a known precursor and sequela of cardiovascular disease (CVD), with ED severity predicting CVD severity.

AIM: This study aimed to evaluate the utility of ceramide levels in patients with ED.

METHODS: We initiated ceramide testing in all patients with ED. We retrospectively analyzed ceramide levels from electronic records and stratified by severity of symptoms using the erectile function domain of the International Index of Erectile Function (IIEF).

OUTCOMES: The study aimed to determine whether abnormal ceramide levels were associated with ED severity and increased cardiovascular risk.

RESULTS: Three hundred and fifty-four patients were reviewed, of whom 253 (71.5%) had moderate or higher ED. A statistically significant difference in abnormal ceramide values was found in patients with moderate to severe symptoms, and the odds of getting an abnormal ceramide test were increased based on the IIEF scoring alone (odds ratio [OR] 2.3 [1.04-5.12]; P-value = .034).

CLINICAL IMPLICATIONS: Serum ceramide testing could be beneficial in identifying cardiovascular risk in men with ED, potentially prompting cardiac referrals and lifestyle modifications.

STRENGTHS AND LIMITATIONS: The strengths of this study include a large sample size and the use of a well-established scale, while the limitations include the retrospective nature of the study and the need for further research to validate the findings.

CONCLUSION: Patients undergoing management for ED may benefit from serum ceramide testing and subsequent cardiac referral.

PMID:41046349 | DOI:10.1093/jsxmed/qdaf182

Cancer Rep (Hoboken). 2025 Oct;8(10):e70357. doi: 10.1002/cnr2.70357.

ABSTRACT

PURPOSE: Acinic cell carcinoma (ACC) of the breast is a very rare, primary salivary gland-type breast malignancy, with ~100 reported cases in the literature. Limited information about the clinical features and outcomes of patients with ACC is available.

METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify ACC patients. For comparison, we also examined a cohort of invasive breast carcinomas of no special type (NST).

RESULTS: Thirty ACC patients were identified among the more than 248 000 invasive breast carcinoma NST patients. ACCs were predominantly grade 3 carcinomas (44%) and were diagnosed at an earlier stage (67%). Hormone receptor (HR) and HER2 status data were available for only 13 patients, revealing molecular heterogeneity: HR-/HER2- (four patients), HR-/HER2+ (two patients), HR+/HER2- (four patients), and HR+/HER2+ (three patients). The median survival time for ACC patients was 19 months vs. 48 months for NST patients (p < 0.001). A complete-case approach was utilized for the adjusted analyses, restricting the sample to 46 257 patients without missing data on all relevant covariates. The adjusted Kaplan-Meier analysis indicated a more pronounced decline in survival probabilities among patients with ACC compared to those with NST, with the number at risk in the ACC group diminishing to four patients by the 30-month mark. In contrast, NST patients exhibited a more gradual decrease. In the multivariable Cox regression, which adjusted for age, TNM stage, HR/HER2, and chemotherapy, ACC histology was correlated with a 1.69-fold increase in the hazard of death (HR: 1.69; 95% CI: 0.63-4.56), although this result was not statistically significant. Age and advanced stage continued to be strong predictors of poor survival, and the inclusion of an age-time interaction enhanced the model fit.

CONCLUSION: Acinic cell carcinoma of the breast is a very rare primary breast malignancy. Our study indicates potentially aggressive clinical behavior in mammary ACC; however, findings must be interpreted cautiously given inherent SEER limitations, especially regarding histologic and molecular subtyping accuracy. Further centralized studies are urgently needed for the accurate characterization of this rare entity.

PMID:41046342 | DOI:10.1002/cnr2.70357

Clin Oral Implants Res. 2025 Oct 4. doi: 10.1111/clr.70053. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the impact of the marginal fit of implant-supported prostheses (ISP) on peri-implant bone levels. Additionally, the study aimed to determine a clinically relevant threshold for the radiographic vertical misfit gap at the ISP, when present, and to identify potential risk factors associated with changes in bone levels.

METHODS: This study involved subjects who received ISPs for tooth replacement therapy. Standardized intraoral periapical radiographs were taken 10 years after loading to assess the radiographic distance between the implant shoulder and the most coronal point of crestal bone (DIB). ISP marginal gaps were categorized as no gap or gap, with vertical dimensions categorized as 0 mm, > 0- < 0.1 mm, and ≥ 0.1 mm. A multivariable linear mixed-effect model was applied to control for potential confounders.

RESULTS: A total of 301 patients and 505 implants with a 10.6 ± 0.7 years follow-up were analyzed. ISPs without gaps exhibited statistically significantly lower DIB values (3.22 ± 0.8 mm) than those with gaps (3.43 ± 0.6 mm; p = 0.001). Gaps ≥ 0.1 mm were associated with statistically significantly higher DIB values (3.45 ± 0.7 mm; p = 0.001) compared with gaps between > 0 and < 0.1 mm (3.36 ± 0.5 mm; p = 0.001), or no gaps (3.22 ± 0.7 mm; p = 0.001). Each increment of 0.1 mm in the vertical crestal gap corresponded to a significant increase in DIB values (0.08 mm; p = 0.03). Finally, smoking and a history of periodontitis were independent risk factors for increased DIB.

CONCLUSIONS: Marginal misfit of ISP affects peri-implant bone stability, with gaps ≥ 0.1 mm linked to higher DIB. Smoking and periodontitis are independent risk factors for increased DIB.

PMID:41046331 | DOI:10.1111/clr.70053