Tag: pubmed

Nat Commun. 2026 Jun 30. doi: 10.1038/s41467-026-74759-6. Online ahead of print.

ABSTRACT

The Mid-Pleistocene Transition ( ~ 1200-650 ka) marked a shift to 100-kyr glacial cycles, despite no significant change in insolation cyclicity. In this study, a high-resolution pollen record from the southwestern Iberian margin, combined with climate modeling, reveals a three-phase climate evolution linked to boreal summer insolation amplitude. In the early phase ( ~ 1200-930 ka), strong insolation minima shifted westerlies north, boosting ice accumulation, while maxima promoted melting, limiting ice growth. The middle phase ( ~ 930-790 ka) followed regoliths loss and featured weaker insolation extremes, leading to the southward migration of the westerlies, mega-droughts and greater ice buildup. In the late phase ( ~ 790-680 ka), stronger minima pushed westerlies north, aligning with longer, colder glacials. These findings suggest that changes in insolation amplitude drove shifts in westerly wind patterns, influencing hydroclimate and ice sheet development, and may have contributed to the transition to 100-kyr glacial cycles.

PMID:42380158 | DOI:10.1038/s41467-026-74759-6

Sci Data. 2026 Jun 30. doi: 10.1038/s41597-026-07680-8. Online ahead of print.

ABSTRACT

Long-term deep ocean temperature monitoring is crucial for understanding the ocean’s role in climate variability and storage of heat in the deep ocean. Observation of the ocean surface is relatively accessible via both in-situ and remote sensing; however, continuous, high-temporal resolution, decade-long temperature records from abyssal depths face the technical challenges of sustained deep ocean deployments. The addition of calibrated, internally-recording temperature sensors to deep-ocean moorings not far from the sea floor provides a means of making high temporal resolution temperature observations. Quality controlling and merging records from successive mooring deployments results in a decade-long time series. Our work has been to optimize approaches for ensuring data quality and continuity in multi-year deep ocean temperature datasets. Here we show a comprehensive processing framework that yields 13 years (2012 to 2025) of continuous temperature measurements at approximately 4200 to 4500 meters depth from the Stratus Ocean Reference Station near 22 °S, 85 °W, 1500 km off the coast of Chile in the Southeast Pacific. Our framework incorporates timing checks, automated spike detection, systematic multi-sensor validation, statistical validation, human-in-the-loop quality control, and merging protocols. This framework establishes reproducible standards for processing long term oceanographic observations from multiple deployments. For the Stratus data set, the result is a unique, decade-long abyssal temperature record with quantified uncertainties that constitutes a benchmark time series for evaluating the realism of deep ocean temperature in models.

PMID:42380150 | DOI:10.1038/s41597-026-07680-8

Stat Med. 2026 Jul;45(15-17):e70657. doi: 10.1002/sim.70657.

ABSTRACT

We apply covariate adjustment to the Wilcoxon two sample statistic and Wilcoxon-Mann-Whitney test in comparing two treatments. The covariate adjustment through calibration not only improves efficiency in estimation/inference but also widens the application scope of the Wilcoxon two sample statistic and Wilcoxon-Mann-Whitney test to situations where covariate-adaptive randomization is used. We motivate how to adjust covariates to reduce variance, establish the asymptotic distribution of adjusted Wilcoxon two sample statistic, and provide explicitly the guaranteed efficiency gain. The asymptotic distribution of adjusted Wilcoxon two sample statistic is invariant to all commonly used covariate-adaptive randomization schemes so that a unified formula can be used in inference regardless of which covariate-adaptive randomization is applied.

PMID:42380083 | DOI:10.1002/sim.70657

Photobiomodul Photomed Laser Surg. 2026 Jun 30:25785478261465275. doi: 10.1177/25785478261465275. Online ahead of print.

ABSTRACT

BACKGROUND: Lumbar disc herniation (LDH) is a prevalent major cause of low back pain and radicular syndromes in the lower extremities. Elevated disc herniation volumes and the subsequent progression of spinal canal compromise are positively correlated with higher severity of radicular symptoms, functional disability, and neurological deficits.

OBJECTIVE: To investigate the impact of high-intensity laser therapy (HILT) on disc size and functional outcomes in patients with LDH.

METHODS: This study enrolled 40 patients of both sexes (40% male and 60% female), ages from 30 to 45 years, all presenting with lumbosacral radiculopathy secondary to L4-L5 or L5-S1 disc herniation. Participants were randomly assigned to two equal groups. Group A (study group) received HILT group treated with a combined standard physical therapy exercise program, while Group B (control group) underwent a sham HILT procedure alongside the same physical therapy exercise program. Interventions were conducted three times a week over 6 weeks. The primary outcome was the change in disc herniation size in anteroposterior, transverse, and posterior vertical diameter as measured by magnetic resonance imaging. The secondary outcomes included pain intensity assessed by the visual analogue scale (VAS) and functional disability assessed by the Oswestry Disability Index (ODI).

RESULTS: The HILT group demonstrated statistically significant reductions in all disc size parameters compared to the control group (p < 0.05). Additionally, the HILT group showed significantly higher reduction in VAS scores (63.88% vs. 26.04%) and ODI scores (53.5% vs. 24.58%) compared with the control group (p < 0.001).

CONCLUSION: HILT serves as a potent noninvasive modality for reducing the herniated lumbar discs size and providing significant pain relief and improving functional outcomes in individuals with lumbosacral radiculopathy.

PMID:42380073 | DOI:10.1177/25785478261465275

Ther Apher Dial. 2026 Jun 30. doi: 10.1002/1744-9987.70178. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic micro-inflammation in patients with end-stage renal disease (ESRD) is a significant driver of cardiovascular complications and diminished quality of life. While standard hemodialysis (SHD) effectively manages small-molecule clearance, its ability to remove medium-to-large uremic toxins-the primary catalysts of systemic inflammation-remains limited. This study aimed to evaluate the comparative clinical benefits of hemodiafiltration (HDF) and hemoperfusion (HDP) relative to SHD, specifically focusing on inflammatory control, dialysis adequacy, and patient safety.

METHODS: This was a 10-week, single-center, non-randomized prospective observational study evaluating 365 end-stage renal disease (ESRD) patients divided into three cohorts: standard hemodialysis (SHD, n = 145, thrice-weekly), online hemodiafiltration (HDF, n = 115, twice-weekly hemodialysis plus once-weekly HDF), and hemoperfusion (HDP, n = 105, twice-weekly hemodialysis plus once-monthly hemoperfusion). Primary endpoints were restricted to short-term surrogate outcomes, including shifts in serum inflammatory markers (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP)) and clearance adequacy indices (Kt/V, URR).

RESULTS: Baseline characteristics were well-balanced across all three cohorts. Following 10 weeks of treatment, the HDF (84.2%) and HDP (77.1%) groups demonstrated significantly higher effective treatment rates (defined by clinical symptom improvement and biochemical stability, a composite of symptomatic improvement and biochemical stability) compared to the SHD group (61.4%; p < 0.05). Advanced modalities achieved increased association with biomarker reduction of middle-molecule toxins, with HDF showing the most profound reductions in IL-6, TNF-α, and CRP (p < 0.001). Dialysis adequacy was significantly improved in the HDF group, which showed the highest increases in dialysis adequacy. While the incidence of acute complications such as hypotension and muscle cramps did not differ significantly between groups, both HDF and HDP cohorts reported a notable reduction in post-dialysis fatigue compared to SHD (14% and 16% vs. 19%, respectively). However, HDF and HDP cohorts experienced lower incidences of cognitive dysfunction.

CONCLUSIONS: Over a 10-week observation framework, advanced hybrid modalities (HDF and HDP) are independently associated with superior clearance of middle-to-large molecular uremic toxins and attenuated systemic inflammation compared to SHD. However, these short-term surrogate improvements did not translate into a statistically significant reduction in clinical adverse events or post-dialysis fatigue, indicating the need for long-term longitudinal evaluation.

PMID:42380071 | DOI:10.1002/1744-9987.70178

Photobiomodul Photomed Laser Surg. 2026 Jun 30:25785478261465277. doi: 10.1177/25785478261465277. Online ahead of print.

ABSTRACT

PURPOSE: Laser-tissue interactions induce photothermal effects governed by wavelength-dependent absorption and circulation of energy. While 980 nm targets hemoglobin for hemostasis and 1470 nm targets water for vaporization, their synergistic optimization in living liver tissue remains undefined, as existing studies predominantly examine ex vivo models or single wavelengths. This study establishes quantitative relationships between laser parameters and tissue outcomes in an in vivo model.

METHODS: Twenty rabbits (female New Zealand White, 1.5-2 kg) underwent hepatic transection using a 400 μm bare fiber diameter (3 mm tissue distance, 10 mm/s advancement speed) in continuous-wave (CW) and pulsed-modulated (100 ms pulse, 50% duty cycle, 5 Hz) modes. Output power: 980 nm (12-160 W) and 1470 nm (6-48 W), with different dual-wavelength power ratios. Measured outcomes: cutting depth, vaporization depth, coagulation depth, and thermal injury depth (quantified by hematoxylin and eosin staining).

STATISTICS: analysis of variance for continuous variables, chi-square/Fisher’s exact test for categorical variables, and the Mann-Whitney U test for non-normal distributions (p < 0.05).

RESULTS: CW mode achieved greater cutting depth than pulsed-modulated mode (median 943.97 μm vs. 689.43 μm, p < 0.05). In CW mode, 1470 nm-dominated ratios (0:1, 1:1, 1:2, 1:3, 1:4) achieved greater cutting depths than 980 nm alone (1:0). Cutting depth increased with peak power from 6 to 120 W, then decreased at 160 W due to carbonization. At 24 W total power with 1:2 ratio (8 W 980 nm/16 W 1470 nm), cutting depth was 1249.3 ± 15.55 μm, vaporization depth 739.5 ± 35.32 μm, coagulation depth 1302 ± 125.44 μm, and thermal damage 1987.53 ± 154.61 μm.

CONCLUSIONS: The 980/1470 nm wavelength power ratio of 8/16 W in CW mode for liver tissue cutting offers high efficiency, safety, and minimal thermal damage, providing an effective surgical energy device for minimally invasive and precise treatment.

PMID:42380070 | DOI:10.1177/25785478261465277

J Gastroenterol Hepatol. 2026 Jun 30. doi: 10.1111/jgh.70512. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to identify differentially expressed proteins (DEPs) in the gastric mucosa of patients with gastric precancerous lesions, establish a differential protein expression profile, and investigate the associated biological processes.

METHODS: Quantitative proteomic analysis of gastric mucosal tissues from 60 patients-including 20 each diagnosed with chronic atrophic gastritis (CAG), intestinal metaplasia (IM), and low-grade intraepithelial neoplasia (LGIN)-was performed using data-independent acquisition liquid chromatography-tandem mass spectrometry (DIA LC-MS/MS). DEPs were identified using stringent statistical criteria (|log₂fold change [FC]| > 1.2, false discovery rate [FDR] < 0.05). Subsequent bioinformatic analyses included Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, as well as receiver operating characteristic (ROC) curve assessments.

RESULTS: A total of 591 proteins were identified across the CAG, IM, and LGIN groups. Comparative analysis revealed 21 statistically significantly DEPs primarily associated with metabolic pathways, signal transduction, cytoskeletal organization, viral infection, carcinogenesis, endocytosis, and the spliceosome. Notably, Parkinson’s disease protein 7 (PARK7) was consistently downregulated and exhibited differential expression across all three pathological stages.

CONCLUSION: This study delineates characteristic protein alterations in the gastric mucosa throughout the progression of gastric precancerous lesions along the CAG-IM-LGIN sequence. PARK7 demonstrates high diagnostic potential and may serve as a promising biomarker for monitoring disease progression in gastric precancerous conditions.

PMID:42380053 | DOI:10.1111/jgh.70512

Vaccine. 2026 Jun 30;89:128870. doi: 10.1016/j.vaccine.2026.128870. Online ahead of print.

ABSTRACT

BACKGROUND: Newcastle disease virus hexapro spike (NDV-HXP-S) is a recombinant vaccine designed to elicit both systemic and mucosal immunity against SARS-CoV-2. Intramuscular vaccines protect against severe disease but provide limited mucosal protection. We conducted a Phase 1 trial of live NDV-HXP-S administered intranasally (IN), intramuscularly (IM), or simultaneously (IN+IM) in previously vaccinated adults.

METHODS: Thirty-five healthy adults without prior COVID-19 were enrolled at a single site in New York City (Feb 2022-Apr 2024). Participants received low- or high-dose NDV-HXP-S via IN, IM, or IN+IM routes, or placebo. Safety was monitored for 365 days; immune responses in serum and saliva were measured through day 84.

FINDINGS: All 35 participants completed follow-up. NDV-HXP-S was safe and well tolerated, with only grade 1-2 adverse events. Placebo recipients showed waning antibody titers, whereas NDV-HXP-S maintained or boosted serum IgG and neutralizing activity. Salivary sIgA rose modestly. Participants with low baseline CD4+ T-cell activity exhibited increases by day 28. The study was not powered for statistical significance.

INTERPRETATION: Live NDV-HXP-S was safe and well tolerated in this small Phase 1 study. Exploratory immunogenicity analyses showed variable systemic and mucosal responses, supporting further evaluation of updated NDV-HXP-S formulations in larger controlled studies.

FUNDING: Supported by the Icahn School of Medicine Dean’s Philanthropic Fund, CastleVax Inc., Mount Sinai CTSA (UL1TR004419), and philanthropic and federal grants.

TRIAL REGISTRATION: ClinicalTrials.govNCT05181709.

PMID:42378814 | DOI:10.1016/j.vaccine.2026.128870

Vaccine. 2026 Jun 30;89:128889. doi: 10.1016/j.vaccine.2026.128889. Online ahead of print.

ABSTRACT

BACKGROUND: Human papillomavirus (HPV) vaccination is a key component of the World Health Organization’s global strategy for cervical cancer elimination. The effect of malaria, a known immunomodulator, on HPV vaccine immunogenicity is poorly understood. This study assessed the effect of malaria parasitaemia at the time of vaccination on HPV vaccine immune responses among participants in a dose-reduction immunogenicity trial (DoRIS).

METHODS AND FINDINGS: 930 HIV-negative Tanzanian schoolgirls aged 9-14 years were randomised to receive one, two or three doses of Cervarix® or Gardasil®9 (155 per arm) and followed to month (M)36. One-dose and two-dose arms participants were enrolled in a long-term extension and are included in this malaria sub-study. Dried blood spots at each vaccination visit were tested for malaria parasitaemia by quantitative polymerase chain reaction. HPV16/18 antibody responses were measured at M12, 24, 36 and 60. In the one-dose arms, there was no evidence of a difference in antibody geometric mean concentrations (GMC) or avidity index (AI) between participants with and without malaria at the time of vaccination. In the two-dose Cervarix® arm, M36 HPV16 antibody GMCs and AI results were lower in participants with malaria at either vaccination visit (HPV16 GMC ratio = 0.74, 95%CI = 0.55-0.99; AI ratio = 0.95, 95%CI = 0.91-0.99). In the two-dose Gardasil®9 arm, M36 HPV18 antibody GMCs and AI results were lower in participants with malaria at the first vaccine dose than those without malaria (HPV18 GMC ratio = 0.58, 95%CI = 0.37-0.92; AI ratio = 0.93, 95%CI = 0.87-0.99). These trends were also observed at M60.

CONCLUSIONS: Whilst some effect of malaria on antibody responses was observed in the two-dose arms, these were mostly small in magnitude and unlikely to have clinical significance. Single-dose arms results are reassuring but further evaluations in larger populations would be valuable to confirm the findings. The potential for an effect of moderate or severe infection with greater parasite burden remains unclear. (NCT02834637).

PMID:42378813 | DOI:10.1016/j.vaccine.2026.128889

Public Health. 2026 Jun 30;258:106391. doi: 10.1016/j.puhe.2026.106391. Online ahead of print.

ABSTRACT

OBJECTIVES: Antimicrobial resistance (AMR) is a major global health threat, largely driven by inappropriate and excessive antibiotic use. Italy has historically reported antibiotic consumption rates above the European average, especially in primary care. In 2017, Italy implemented the National Action Plan on Antimicrobial Resistance (NAP-AMR), including targets for reducing overall community antibiotic and fluoroquinolone use. This study evaluated the impact of NAP-AMR on antibiotic consumption trends in Italian primary care from 1999 to 2024.

STUDY DESIGN: Quasi-experimental interrupted time series study.

METHODS: Annual ECDC data were expressed as defined daily doses (DDD) per 1000 inhabitants per day. Total antibiotic consumption was analyzed for 1999-2024 and fluoroquinolone consumption for 2005-2024. Segmented linear regression with Newey-West standard errors estimated post-2017 changes in level and trend. Total systemic antibiotic consumption was the primary outcome, and fluoroquinolone consumption was the secondary outcome.

RESULTS: Total antibiotic consumption showed a significant pre-intervention upward trend, increasing annually by 0.10 DDD per 1000 inhabitants per day (annual change = 0.096; p = 0.032; 95% CI: 0.014 to 0.178). NAP-AMR implementation was associated with a significant immediate reduction in total antibiotic use (mean level difference = -4.940; p = 0.003; 95% CI: -7.864 to -2.016), while the post-intervention slope change was not significant (annual change = 0.126; p = 0.606; 95% CI: -0.346 to 0.599). Fluoroquinolone consumption showed a significant pre-intervention upward trend (annual change = 0.039; p = 0.016; 95% CI: 0.011 to 0.066) and a significant immediate reduction (mean level difference = -1.079; p = 0.023; 95% CI: -1.910 to -0.248). The post-intervention trend was negative but not significant (annual change = -0.219; p = 0.096; 95% CI: -0.459 to 0.021).

CONCLUSIONS: NAP-AMR was associated with immediate reductions in total antibiotic and fluoroquinolone consumption, but sustained trend changes were not statistically significant. No significant long-term trend change was observed, underscoring ongoing surveillance and future evaluation.

PMID:42378783 | DOI:10.1016/j.puhe.2026.106391