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Slow-release L-cysteine Lozenges in Smoking Cessation: Meta-analysis of Two Randomized Controlled Trials

In Vivo. 2026 Jan-Feb;40(1):39-49. doi: 10.21873/invivo.14171.

ABSTRACT

BACKGROUND/AIM: The hypothesis that elimination of cigarette smoke-derived acetaldehyde in the saliva by slow-release L-cysteine would eliminate acetaldehyde-enhanced nicotine addiction among smokers has been tested in two randomized controlled trials (RCT) using Acetium® lozenge (Biohit Oyj, Helsinki, Finland). Both RCTs showed a similar direction and magnitude of the effect size, but only the larger study was adequately powered to reach statistical significance.

MATERIALS AND METHODS: The two published RCTs on Acetium® in smoking intervention included in this formal meta-analysis include: a cohort of 423 cigarette smokers, randomly allocated to intervention (n=212) and placebo arms (n =211) in Study 1, as well as a cohort of 1,998 smokers, with 996 and 1,002 subjects in the intervention and placebo arms, respectively, in Study 2. Both studies analyzed the results for intention-to-treat (ITT) and per protocol (PP) compliance groups. Random-effects (RE) meta-analysis was used to compute the summary effect size.

RESULTS: In the ITT group of Study 1, Acetium® was more effective than placebo, with OR=1.48 (95% CI=0.87-2.54), and in Study 2, the respective OR=1.26 (95% CI=0.99-1.59). In the PP groups, the success rates in both studies were better: OR=1.65 (95% CI=0.75-3.62) and OR=1.51 (95% CI=1.12-2.02), respectively. In RE meta-analysis, the summary estimates of Acetium® efficacy were statistically significant in both the ITT (n=2,421) and PP (n=863) analysis: OR=1.29 (95% CI=1.04-1.60, p=0.018) and OR=1.53 (95% CI=1.16-2.01, p=0.0025), respectively.

CONCLUSION: Although meta-analyses with a limited number of studies should be interpreted with caution, these data provide clear support to the concept that Acetium® lozenge significantly (1.5-fold) increases the likelihood of successful smoking cessation as compared to placebo.

PMID:41482382 | DOI:10.21873/invivo.14171

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Pregnancy Outcomes Following In Vitro Fertilization: A Multicenter Comparative Analysis Between Donor-oocyte Recipients and Self-oocyte Patients in Greece

In Vivo. 2026 Jan-Feb;40(1):452-464. doi: 10.21873/invivo.14209.

ABSTRACT

BACKGROUND/AIM: Delayed childbearing has increased the reliance on in vitro fertilization (IVF) with donor oocytes for women of advanced maternal age often facing more obstetric complications compared to younger women using self-oocytes. This study evaluated and contrasted key obstetric and perinatal parameters between these two groups.

PATIENTS AND METHODS: In this retrospective multicenter study, completed IVF embryo transfer cycles were analyzed. Clinical data including clinical pregnancy, miscarriage, ectopic pregnancy rates, and major pregnancy complications were collected. Obstetric outcomes (e.g., mode of delivery, preterm birth, and neonatal parameters such as birth weight, Apgar scores, and NICU admissions) were compared between the donor-oocyte recipients (DOR-IVF) and self-oocyte (SO-IVF) groups. Statistical analysis comprised chi-square tests, t-tests, and multivariable logistic and linear regressions to adjust for potential confounders.

RESULTS: The DOR-IVF group demonstrated a clinical pregnancy rate of 44.8% (196 cases) with an 8.8% miscarriage rate, while the SO-IVF group reported 242 clinical pregnancies with an 8.1% miscarriage rate. Overall, nine ectopic pregnancies (2%) were noted, with statistically significant differences in ectopic and miscarriage rates between the groups (p=0.008 and p=0.025, respectively). Although the mean gestational age was similar and NICU admissions did not differ significantly (p=0.125), the DOR-IVF group exhibited a higher incidence of pregnancy complications (p=0.009). Multivariable logistic regression identified DOR-IVF as an independent predictor for pregnancy complications (adjusted odds ratio 2.38; 95% confidence interval=1.53-3.70). Additionally, subgroup analyses revealed that 1-minute Apgar scores were positively associated with DOR-IVF status (p=0.048) and birth weight was inversely related to the number of babies transferred (p=0.006).

CONCLUSION: DOR-IVF patients experience significantly increased risk in obstetric complications compared to younger women using SO-IVF, although neonatal outcomes remain largely similar.

PMID:41482376 | DOI:10.21873/invivo.14209

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VEGF-C Aqueous Humor Levels in Patients With Primary Open Angle Glaucoma

In Vivo. 2026 Jan-Feb;40(1):382-388. doi: 10.21873/invivo.14202.

ABSTRACT

BACKGROUND/AIM: This study aimed to quantitatively analyze and compare aqueous humor concentrations of vascular endothelial growth factor-C (VEGF-C) in patients with primary open-angle glaucoma (POAG) versus non-glaucomatous controls while evaluating potential significant correlations.

PATIENTS AND METHODS: We conducted an observational cross-sectional study. At surgery initiation, anterior chamber paracentesis was performed under sterile conditions, and 50-100 μl of aqueous humor samples were collected. VEGF-C quantification employed a multiplex magnetic bead immunoassay platform.

RESULTS: The study involved the collection of aqueous humor samples from 76 participants: 39 samples were collected from the POAG group and 37 from the control group (age-related cataract). Quantitative analysis revealed mean VEGF-C concentrations of 26.41±26.016 pg/ml in POAG eyes compared to 16.70±8.60 pg/ml in controls (p=0.277), demonstrating no statistically significant difference. Receiver operating characteristic (ROC) curve analysis showed limited prognostic ability for POAG detection (AUC=0.60; p=0.278).

CONCLUSION: This study represents the first large-scale evaluation of aqueous humor VEGF-C levels in patients with POAG. Our results provide evidence against VEGF-C up-regulation in POAG.

PMID:41482375 | DOI:10.21873/invivo.14202

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Effects of Intravenous Laser Irradiation of Blood on Metabolic Markers in Patients With Hyperlipidemia: A Retrospective Pilot Study

In Vivo. 2026 Jan-Feb;40(1):495-501. doi: 10.21873/invivo.14213.

ABSTRACT

BACKGROUND/AIM: Hyperlipidemia is a major risk factor for cardiovascular diseases. Pharmacological treatment and lifestyle modifications are the main therapeutic approaches; however, some patients respond poorly or have limited tolerance. Intravenous laser irradiation of blood (ILIB) has recently been proposed as a potential adjunctive therapy, but its clinical efficacy remains unclear. The aim of this study was to evaluate the effects of ILIB therapy on lipid profiles and glycemic parameters in patients with chronic diseases.

PATIENTS AND METHODS: This retrospective single-group study included 60 patients with chronic diseases who received ILIB therapy at the Chang Bing Show Chwan Memorial Hospital between July 2022 and February 2024. Laboratory parameters before and after treatment, including total cholesterol, triglycerides (TG), LDL-C, fasting glucose, and HbA1c, were descriptively compared to demonstrate absolute and percentage changes. Paired t-test and Wilcoxon signed-rank test were used, with p<0.05 considered statistically significant.

RESULTS: After treatment, only TG showed a significant reduction (167.8 mg/dl vs. 118.8 mg/dl, p=0.001). Subgroup analysis revealed that patients with TG >150 mg/dL, LDL>130 mg/dl, and total cholesterol >200 mg/dl all demonstrated significant decreases after ILIB therapy (p<0.05), while no significant changes were observed in patients with normal baseline values. Fasting glucose and HbA1c showed no significant changes in any subgroup.

CONCLUSION: ILIB demonstrated significant lipid-lowering effects in patients with dyslipidemia, particularly in those with elevated TG, LDL, and total cholesterol. No changes were observed in patients with normal lipid levels, suggesting a “normalizing” rather than broadly “lowering” effect. ILIB shows promise as an adjunctive therapy for hyperlipidemia, though larger randomized controlled trials are warranted to confirm these findings.

PMID:41482358 | DOI:10.21873/invivo.14213

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Mutational Spectrum of T-Cell Large Granular Lymphocytic Leukemia: Insights From the AACR Project GENIE Consortium

Cancer Genomics Proteomics. 2026 Jan-Feb;23(1):135-143. doi: 10.21873/cgp.20566.

ABSTRACT

BACKGROUND/AIM: T-cell large granular lymphocyte leukemia (T-LGLL) is a rare, indolent lymphoproliferative disorder of cytotoxic T cells in the peripheral blood, bone marrow, and spleen. This analysis was conducted to characterize genomic alterations and highlight potential therapeutic targets, with the goal of refining the molecular landscape of T-LGLL by emphasizing population-specific biomarkers.

MATERIALS AND METHODS: This study utilized the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database to identify common gene mutations. Using the AACR GENIE database, a retrospective analysis of T-cell large granular lymphocyte leukemia (T-LGLL) samples was performed. The data was evaluated by extracting patient demographics and excluding synonymous mutations from consideration. Statistical significance was assessed using chi-squared tests and computational analyses in RStudio (R Foundation for Statistical Computing, Boston, MA, USA). Somatic mutations and chromosomal copy number variations were evaluated, with statistical significance defined as p=0.001.

RESULTS: Frequently observed somatic mutations included STAT3 (41.7%), STAT2 (20.9%), KMT2D (11.3%), SETD1B (8.7%), TP53 (7.0%), TNFAIP3 (6.1%), DNMT3A (5.2%), FAS (4.3%), SMARCA4 (3.5%), EPHB1 (2.6%), KSR2 (2.6%), ALOX12B (2.6%), EGFR (2.6%), DDX3X (7.0%), and IKZF3 (1.7%). When stratified by demographic variables, males and White patients demonstrated a higher frequency of mutations.

CONCLUSION: This study provides a comprehensive genomic profile of T-LGLL, identifying recurrent somatic mutations and commonly affected pathways. Notably, frequent alterations were observed in the FASFASL signaling pathway, underscoring its potential as a target for therapeutic development.

PMID:41482347 | DOI:10.21873/cgp.20566

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Energy Spectrum of Ultrahigh-Energy Cosmic Rays across Declinations -90° to +44.8° as Measured at the Pierre Auger Observatory

Phys Rev Lett. 2025 Dec 12;135(24):241002. doi: 10.1103/p4l5-hxlf.

ABSTRACT

The energy spectrum of cosmic rays above 2.5 EeV has been measured across the declination range -90°≤δ≤+44.8° using ∼310 000 events accrued at the Pierre Auger Observatory from an exposure of (104 900±3 100) km^{2} sr yr. No significant variations of energy spectra with declination are observed, after allowing or not for nonuniformities across the sky arising from the well-established dipolar anisotropies in the arrival directions of ultrahigh-energy cosmic rays. The instep feature in the spectrum at ≃10 EeV reported previously is now established at a significance above 5σ. Within the statistics, the energy spectra are indistinguishable across declinations so disfavoring an origin for the instep from a few distinctive sources.

PMID:41482327 | DOI:10.1103/p4l5-hxlf

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Active Quantum Flocks

Phys Rev Lett. 2025 Dec 12;135(24):248302. doi: 10.1103/rd46-hr3q.

ABSTRACT

Flocks of animals represent a prominent archetype of collective behavior in the macroscopic classical world, where the constituents, such as birds, concertedly perform motions and actions as if being one single entity. Here, we address the so far open question of whether flocks can also form in the microscopic world at the quantum level. For that purpose, we introduce the concept of active quantum matter by formulating a class of models of active quantum particles on a one-dimensional lattice. We provide both analytical and large-scale numerical evidence that these systems can give rise to quantum flocks. A key finding is that these quantum flocks exhibit distinct quantum properties by developing strong quantum coherence over long distances. We propose that quantum flocks could be experimentally observed in Rydberg atom arrays.

PMID:41482319 | DOI:10.1103/rd46-hr3q

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Exact Non-Markovian Master Equations: A Generalized Derivation for Gaussian Systems

Phys Rev Lett. 2025 Dec 12;135(24):240401. doi: 10.1103/cb7c-5f66.

ABSTRACT

We derive an exact master equation that captures the dynamics of a quadratic quantum system linearly coupled to a Gaussian environment of the same statistics: the Gaussian master equation (GME). Unlike previous approaches, our formulation applies universally to both bosonic and fermionic setups, and remains valid even in the presence of initial system-environment correlations, allowing for the exact computation of the system’s reduced density matrix across all parameter regimes. Remarkably, the GME shares the same operatorial structure as the Redfield equation and depends on a single kernel: a dressed environment correlation function accounting for all virtual interactions between the system and the environment. This simple structure grants a clear physical interpretation and makes the GME easy to simulate numerically, as we show by applying it to an open system based on two fermions coupled via superconductive pairing.

PMID:41482302 | DOI:10.1103/cb7c-5f66

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Comparative analysis of phytochemicals in different plant organs of Verbascum thapsus L. by using UPLC/MS-QToF and analytical standardization of bioactive compounds, verbascoside and luteolin, on HPLC platform

Nat Prod Res. 2026 Jan 2:1-10. doi: 10.1080/14786419.2025.2601253. Online ahead of print.

ABSTRACT

Verbascum thapsus L., commonly called Mullein, is widely used in Ayurveda for the treatment of numerous ailments. The major objective of the present study is to analyse the phytochemical composition of different plant organs of V. thapsus. UPLC/MS-QToF analysis of methanol extracts from different plant organs (inflorescence, leaf, stem, and root) of V. thapsus displayed 61 active biomarkers. Among those, 48 compounds were found in the inflorescence, 40 in the leaf, 32 in the stem, and 29 in the root of V. thapsus. The distribution of these compounds was further evaluated statistically using Venn and Heat map diagrams. Moreover, a novel reverse-phase HPLC method was developed and validated as per ICH Q2(R1) guidelines to quantify verbascoside and luteolin of V. thapsus. The method was found suitable, specific, linear (R2 > 0.999), precise, accurate, and robust. The current study’s novel findings can help with the identification and quality control of verbascoside and luteolin in plant species used in Ayurvedic medicines.

PMID:41481338 | DOI:10.1080/14786419.2025.2601253

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Clinical Trial Termination or Withdrawal in Head and Neck Squamous Cell Carcinoma

JAMA Otolaryngol Head Neck Surg. 2026 Jan 2. doi: 10.1001/jamaoto.2025.4766. Online ahead of print.

ABSTRACT

IMPORTANCE: Innovative clinical trials (CTs) are needed to address the rising incidence of head and neck squamous cell carcinoma (HNSCC). Despite adequate trial initiation, HNSCC CTs experience high failure rates, and the factors driving these trends remain unclear.

OBJECTIVE: To assess the characteristics associated with failure (termination or withdrawal) in CTs for the treatment of HNSCC.

DESIGN AND SETTING: HNSCC CTs were identified on ClinicalTrials.gov from January 1, 2000, to December 31, 2024, and trial failures were defined as early termination or withdrawal. Trial characteristics were compared between failed CTs and completed CT controls. Data were analyzed from June to August 2025.

MAIN OUTCOMES AND MEASURES: The primary outcome was trial failure. The association between failure and CT characteristics, including phase, enrollment, funding source, intervention type, and age-eligibility criteria, was analyzed using descriptive statistics and multivariable regression models.

RESULTS: A total of 692 matched trials were analyzed, including 346 trial failures and 346 completed control trials. The overall leading reasons for failure were strategic decisions (defined as nonscientific, sponsor-driven choices; 102 trials [29.5%]) and poor recruitment (90 trials [26.0%]). The reasons for failure varied by trial characteristics. Strategic decisions were the predominant reason for failure in phase 1 trials, industry-sponsored trials, and immunotherapy and targeted therapy trials. In contrast, poor recruitment was a more common reason in later-phase trials, non-industry-sponsored trials, and trials investigating chemotherapy, radiation, chemoradiation, combination treatments, and supportive care. Temporal analysis revealed a growing failure rate among CTs since 2000. Increased log-transformed actual enrollment safeguarded against trial failure, whereas industry funding was an independent risk factor.

CONCLUSIONS AND RELEVANCE: In this study, HNSCC CTs were terminated early or withdrawn for a variety of reasons, most commonly due to strategic decisions or poor recruitment. Careful attention to trial characteristics associated with early failure is needed to overcome new barriers to drug development and adapt trial design to common reasons for failure.

PMID:41481330 | DOI:10.1001/jamaoto.2025.4766