Nevin Manimala

Adv Sci (Weinh). 2026 Jun 18:e76142. doi: 10.1002/advs.76142. Online ahead of print.

ABSTRACT

Spatial transcriptomics (ST) enables the study of tissue architecture by resolving gene expression in space, but current ST platforms are constrained by limited sequencing depth and indirect single-cell identification. Existing deconvolution methods that integrate single-cell RNA sequencing (scRNA-seq) data with ST often overlook the biological principle that cells in communication with each other tend to be closer spatially. Here we introduce SPADE, a deep learning framework that aligns scRNA-seq data to spatial locations by jointly modeling expression similarity between scRNA-seq and ST data and concordance between the spot distance and cell-cell communication (CCC) patterns. SPADE also enables quantitative characterization of CCC across spots and regions. Evaluations on 55 simulated and real datasets show that SPADE achieves strong performance in recovering region-specific cell-type patterns and enhancing spatial gene expression profiles compared with existing methods. In the breast cancer datasets, SPADE demonstrates a unique advantage in identifying tumor-infiltrating immune cells and tertiary lymphoid structures. In the colorectal cancer liver metastasis dataset, SPADE distinguishes tumor heterogeneity with region-specific CCC events and describes the general CCC landscape in the tissue. Overall, SPADE highlights the key role of spatially constrained CCC in shaping tissue organization and enables biological interpretation of spatial transcriptomics data.

PMID:42314058 | DOI:10.1002/advs.76142

JMIR Form Res. 2026 Jun 18;10:e82923. doi: 10.2196/82923.

ABSTRACT

BACKGROUND: The clinical diagnosis rate of adenoid hypertrophy (AH) in children has increased in recent years, drawing growing attention from parents. Short-video platforms such as Bilibili, TikTok, and Xiaohongshu host a large volume of educational content on this condition. However, the quality and reliability of this information remain unclear.

OBJECTIVE: This study aimed to evaluate the completeness, understandability, actionability, reliability, and overall quality of short videos on AH across Bilibili, TikTok, and Xiaohongshu and to explore factors associated with these quality metrics, including uploader characteristics and engagement indicators.

METHODS: We collected 220 videos (Bilibili: n=90, 40.9%; TikTok: n=63, 28.6%; and Xiaohongshu: n=67, 30.5%) using newly registered accounts. Two independent reviewers evaluated video quality using a 6-item content completeness scale (score range 0-12), the Patient Education Materials Assessment Tool for Audiovisual Materials, the modified DISCERN instrument, and the Global Quality Scale (GQS). Interrater reliability was high (Cohen κ=0.77-0.993). Completeness assessed essential informational components of AH. As data were nonnormally distributed, results are presented as median (IQR). Cross-platform comparisons were conducted using the Kruskal-Wallis H test with post hoc Mann-Whitney U tests (with Bonferroni correction). Spearman correlation was used to explore associations between video characteristics (ie, duration and engagement metrics) and quality outcomes. Stepwise linear regression identified independent predictors of overall quality (GQS).

RESULTS: Video duration differed significantly across platforms (Bilibili: median 113.5, IQR 66.5-271.5 seconds; TikTok: median 73, IQR 44-100 seconds; and Xiaohongshu: median 63, IQR 41-127.5 seconds; P<.001). Bilibili videos demonstrated higher completeness than videos on the other 2 platforms (Bilibili: median 2, IQR 1.5-4.0; TikTok: median 1.5, IQR 0.5-2.0; and Xiaohongshu: median 1.5, IQR 0.5-2.8; P<.001); overall differences were observed for understandability and reliability, but pairwise comparisons did not reach statistical significance after Bonferroni correction. Xiaohongshu videos showed greater actionability than TikTok videos (P=.011). Medical professionals (n=158, 71.8%) had higher understandability than nonprofessionals (n=158, 81.8% vs n=62, 66.7%; P=.001). Video duration positively correlated with completeness (ρ=0.64, 95% CI 0.56-0.71; P<.001). Shares showed weak positive correlations with completeness and actionability. Stepwise regression identified understandability (using the Patient Education Materials Assessment Tool-Understandability) as the strongest independent predictor of overall quality (GQS), followed by actionability, video duration, and uploader type; engagement metrics and platform did not enter the final model.

CONCLUSIONS: The quality of AH-related videos on Chinese short-video platforms is generally suboptimal. Bilibili offers higher completeness, while Xiaohongshu excels in actionability and interactivity. Understandability is the strongest predictor of overall quality, surpassing uploader type and engagement metrics. To improve online health information, platforms should move beyond engagement-based algorithms, and health care professionals should prioritize clear, actionable content.

PMID:42314031 | DOI:10.2196/82923

Prostate. 2026 Jun 18. doi: 10.1002/pros.70210. Online ahead of print.

ABSTRACT

BACKGROUND: PI-RADS 3 lesions represent a diagnostic “gray zone” in which biopsy decision-making is particularly challenging, with reported clinically significant prostate cancer (csPCa) detection rates ranging from 13% to 50%. This study evaluated the predictive value of the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR)-alone and in combination with PSA density (PSAD) and PI-RADS score-for the detection of prostate cancer (PCa) and csPCa, with a specific focus on the PI-RADS 3 subgroup.

METHODS: In this two-center retrospective observational study, 982 patients who underwent prostate biopsy between 2020 and 2025 were included. csPCa was defined as ISUP Grade Group ≥ 2. Univariable and multivariable logistic regression analyzes were performed to identify independent predictors of PCa and csPCa. In the PI-RADS 3 subgroup (n = 251), two predictive models were compared using receiver operating characteristic analysis and the DeLong test: Model 1 (age, free/total PSA ratio, PSAD) and Model 2 (Model 1 + SII + NLR).

RESULTS: Of the 982 patients, 188 (19.1%) were diagnosed with PCa and 150 (15.3%) with csPCa. In the overall cohort, NLR ≥ 2.11 was independently associated with csPCa (OR, 15.924; 95% CI, 2.472-102.567; p = 0.004), whereas SII did not retain independent significance. PLR showed an inverse association with PCa, possibly reflecting tumor-related platelet dynamics. In the PI-RADS 3 subgroup, SII ≥ 661.37 (OR, 2.317; p = 0.039) remained an independent predictor of PCa alongside age, free/total PSA ratio, and PSAD ≥ 0.20 (OR, 6.111; p = 0.013), while NLR showed borderline significance. The addition of SII and NLR to the clinical model increased the AUC from 0.795 to 0.816 in the PI-RADS 3 subgroup, although this improvement did not reach statistical significance (p = 0.134).

CONCLUSIONS: Systemic inflammatory markers-particularly SII and NLR-provide complementary predictive information in the pre-biopsy risk stratification of prostate cancer. SII emerged as an independent predictor of PCa specifically within the PI-RADS 3 gray zone, while NLR independently predicted csPCa in the overall cohort. These routinely available, low-cost parameters may serve as practical adjuncts to PSA derivatives and mpMRI in the individualization of biopsy decisions, particularly for PI-RADS 3 patients.

PMID:42314010 | DOI:10.1002/pros.70210

JMIR Res Protoc. 2026 Jun 18;15:e99833. doi: 10.2196/99833.

ABSTRACT

BACKGROUND: Chronic pain affects over 30% of the global population and remains a major public health issue due to limited treatment efficacy and the need for mechanism-based, personalized approaches. Motor behavior is theorized to play a role in pain persistence through altered movement patterns, muscle recruitment, and proprioception. While motor behavior is linked to chronic pain, empirical evidence on underlying mechanisms, particularly cortical dynamics, remains scarce.

OBJECTIVE: This study aimed to investigate longitudinal changes in cortical sensorimotor excitability and their relationship with maladaptive motor behaviors.

METHODS: This prospective longitudinal study will follow 150 healthy participants, aged 18-65 years, recruited from the community, experiencing experimentally induced muscle pain across 4 visits (day 0, day +2, day +4, and 5 days after pain resolution). Pain will be induced using intramuscular injections of nerve growth factor into the extensor carpi radialis brevis muscle. The primary outcome is motor variability assessed during multidimensional wrist movement tasks, and quantified using root-mean-square deviation and muscle synergies (derived from electromyographic recordings of 4 forearm muscles). Secondary outcomes include cortical mechanisms (electroencephalographic peak alpha frequency, transcranial magnetic stimulation mapping, short-interval intracortical inhibition, and intracortical facilitation), sensorimotor integration (evoked potential), cognitive control (multisource interference task), and endogenous pain modulation (conditioned pain modulation). Self-report questionnaires will assess pain intensity and disability (Patient-Rated Tennis Elbow Evaluation, McGill Pain Questionnaire-Short Form, and Likert Muscle Soreness Scale) as well as psychological factors such as fear of movement, pain-related beliefs, and coping strategies (Tampa Scale for Kinesiophobia, Pain Beliefs Questionnaire, and Coping Strategies Questionnaire-Revised). This sample size provides 80% power at 5% significance to detect a medium effect size across 23 predictor variables, with Bonferroni correction and 10% loss-to-follow-up allowance. Data will be analyzed using 2-level growth curve modeling to characterize interindividual differences in motor behavior, cortical dynamics, and pain processing trajectories.

RESULTS: All study procedures have been approved by the Western University Health Science Research Ethics Board (review reference 2025-125757-103291). Funding was provided by the Canadian Institutes of Health Research under grant number 517783 for the period 2024-2029. Recruitment for the study began in April 2025, and all data collection is expected to be completed by 2028. As of April 2026, we have enrolled 26 participants. Results are expected to be published at the end of 2028.

CONCLUSIONS: The findings will advance understanding of motor behavior in pain and lay the foundation for personalized therapies, moving beyond current generic treatments that offer limited benefits.

PMID:42313885 | DOI:10.2196/99833

Clin Transl Allergy. 2026 Jun;16(6):e70176. doi: 10.1002/clt2.70176.

ABSTRACT

BACKGROUND: Multiple routes of allergen immunotherapy (AIT) are approved for several IgE-mediated allergic diseases; however, the use of AIT in eosinophilic esophagitis (EoE) remains controversial and is supported by limited evidence. This review, conducted within the frame of an EAACI Task Force, aims to systematically evaluate the use of AIT as a potential treatment for EoE.

METHODS: The protocol was registered and prepared in accordance with PRISMA guidelines. The literature search was conducted across three online databases (PubMed, Embase, and Scopus) and included studies published through January 31^st, 2025. Risk of Bias was assessed for each eligible study.

RESULTS: Four articles met the inclusion criteria. Three articles evaluated EPIT for milk-induced EoE in pediatric patients, all from the SMILEE (Study of Efficacy and Safety of Viaskin Milk for milk-induced EoE) trial and its extensions. These included a randomized, placebo-controlled trial, its open-label extension, and a pilot immunological study. The SMILEE trial found no statistically significant difference in tissue eosinophilia between the active (EPIT) and control (placebo) arms in the intention-to-treat population, while 47% of treated EoE patients tolerated milk without recurrence of esophageal eosinophilia. This finding was further supported by a subsequent open-label study with a 2-year follow-up. In the third publication, the researchers found that EPIT was associated with decreased Th2-related transcripts and increased regulatory T-cell-associated transcripts. Only one eligible study evaluated the use of SCIT for treating EoE. It was a retrospective case-control study reporting that SCIT had a neutral effect and yielded inconclusive findings regarding the course of EoE.

CONCLUSION: There is insufficient high-quality evidence to support the effectiveness of alternative routes of AIT for the treatment of EoE, either as an add-on or a standalone treatment.

PMID:42313883 | DOI:10.1002/clt2.70176

Microb Genom. 2026 Jun;12(6). doi: 10.1099/mgen.0.001763.

NO ABSTRACT

PMID:42313461 | DOI:10.1099/mgen.0.001763

J Clin Hypertens (Greenwich). 2026 Jun;28(6):e70284. doi: 10.1111/jch.70284.

ABSTRACT

During exercise, fine hemodynamic adjustments are essential to ensure adequate energy supply. Although cyclic treadmill exercise has been widely studied, isometric exercise with Handgrip (HG) has gained relevance in conditioning and rehabilitation contexts, yet data on the acute hemodynamic effects of combining these modalities remain scarce. In this context, the present study tested the hypothesis that isometric contraction with HG modifies the hemodynamic responses of Heart Rate (HR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Double Product (DP) during cyclic treadmill exercise. A clinical trial was conducted with 40 young, active or irregularly active men, using a crossover design in which three protocols were applied: protocol 1 without HG, protocol 2 with HG at 30% of handgrip strength (HGS), and protocol 3 with HG at 60% of HGS. The exercise sessions were performed on a treadmill and consisted of four blocks of 2 min at 50% of heart rate reserve, followed by 1 min at 30%. Statistical analysis was carried out using Kruskal-Wallis and Friedman tests with appropriate post hoc procedures. The results demonstrated that protocols 2 and 3 significantly increased SBP and DBP compared to protocol 1 (p < 0.05), while DP was significantly higher only in protocol 3 (p < 0.01). Heart rate increased throughout exercise in all protocols (p < 0.05), with no differences between them. Additionally, HG did not modify the hemodynamic response during recovery. Overall, HG promotes increases in SBP, DBP, and DP during treadmill exercise without altering HR.

PMID:42313450 | DOI:10.1111/jch.70284

J Antimicrob Chemother. 2026 Jun 3;81(7):dkag217. doi: 10.1093/jac/dkag217.

ABSTRACT

OBJECTIVES: Quantification of prescription of antimicrobial agents and use of paediatric outpatient services before, during and after the COVID-19 pandemic.

METHODS: We conducted a population-based study using Norwegian linked health registries and Japanese claims (2018-2023). Paediatric antibiotic prescription rates, broad-spectrum use, and proportion of antibiotic prescriptions with prior presumed bacterial infection diagnoses were analysed monthly, overall and by age groups and sex. Interrupted time series analyses were performed to evaluate pandemic-related changes, expressed in rate ratio (RR) and its CI, using March 2020 as the interruption point and the pre-pandemic trend/level as reference.

RESULTS: Data on 5.5 million children and 19.5 million antibiotic prescriptions were analysed. Before the pandemic, antibiotic prescribing was higher in Japan (120-200/1000 children/month) than in Norway (10-20/1000). At pandemic onset, rates fell by 45% in Norway (RR = 0.55; 95% CI, 0.45-0.67) and by 53% in Japan (RR = 0.47; 95% CI, 0.41-0.55), then by 2023 had returned to expected levels. Broad-spectrum antibiotic use was much higher in Japan (70%) compared with Norway (10%) before the pandemic. However, Norway experienced a sharp 20% increase whereas Japan remained largely unchanged post-pandemic. The proportion of prescriptions with a prior presumed bacterial diagnosis was between 50% and 65% before the pandemic then decreased modestly by 5%-10% at pandemic onset, followed by gradual rebound in both countries.

CONCLUSIONS: The COVID-19 pandemic significantly altered paediatric antibiotic prescribing in both countries. Sustained antibiotic stewardship efforts are needed to ensure appropriate paediatric antibiotic use in the post-pandemic era.

PMID:42313421 | DOI:10.1093/jac/dkag217

J Antimicrob Chemother. 2026 Jun 3;81(7):dkag216. doi: 10.1093/jac/dkag216.

ABSTRACT

BACKGROUND: We previously demonstrated in a randomized controlled trial that antibiotic prescribing feedback to family physicians reduced antibiotic use. However, that trial did not evaluate for patient harms from potential under-prescribing of antibiotics.

OBJECTIVES: To evaluate the safety of an antibiotic audit and feedback intervention.

METHODS: We performed a post hoc secondary analysis of a randomized controlled trial that compared an intervention group, who received a mailed antibiotic prescribing peer comparison feedback letter, compared with a control group who did not receive a letter. The initial trial was limited to patients aged 65 years or older due to availability of pharmacy claims data. The primary outcome was an emergency department visit or hospital admission for a bacterial infection. The outcome was assessed at 6 months post-intervention using administrative data claims data and multivariable linear regression models. The initial trial was registered (NCT04594200).

RESULTS: We included 4879 physicians-3909 intervention physicians and 970 control physicians. There were 37 345 severe infection events in the 6 month post-intervention period. The observed mean (SD) of all severe infection events per physician was 7.73 (12.42) for control and 7.64 (11.91) for intervention groups. The model-based adjusted mean difference was -0.23 (95% CI, -0.92 to 0.45; P = 0.505).

CONCLUSIONS: In this post hoc analysis of a randomized controlled trial comparing antibiotic prescribing feedback versus no feedback to physicians in primary care, there was no evidence of severe bacterial infection complications associated with reduced antibiotic prescribing. These findings support antibiotic peer comparison feedback as a safe and effective tool to reduce unnecessary antibiotic prescribing.

PMID:42313420 | DOI:10.1093/jac/dkag216

Account Res. 2026 Jun 18:2691602. doi: 10.1080/08989621.2026.2691602. Online ahead of print.

ABSTRACT

BACKGROUND: Predatory conferences (PCs) scam researchers by compromising them financially and professionally. This study presents the empirical development of the Pre-Attendance Conference Evaluator (PACE) to help academics assess a conference’s legitimacy.

MATERIALS AND METHOD: An expert group of six academics validated a preliminary list of PC traits. After identifying latent constructs through pilot testing, the list underwent four iterations based on statistical factor loadings to assess reliability, predictive validity, and concurrent validity. Later, confirmatory factor analysis included a battery of model-fit indices to assess the scale’s dimensionality.

RESULTS: Content validity ratio and semi-structured interviews reduced the number of PC traits from 70 to 29. Cronbach’s alpha and the Kaiser-Meyer-Olkin test indicated 15 items suitable for factor analysis. Parallel analysis of pilot-testing data from 800 conference-level observations revealed the scale’s unidimensionality. Eventually, 11 items showed strong factor loadings and a high fit across model indices. Concurrent validity assessed by 616 conference-level observations showed high correlations (r_s = 0.73-0.80) with existing tools. High predictive validity (>0.9) and test-retest reliability (ICC = 0.47-0.68) indicated moderate-to-good temporal stability. The ROC analysis yielded a cutoff score of < 14 to deem a conference predatory.

CONCLUSION: PACE demonstrated acceptable validity and reliability as a tool for diagnosing potentially predatory conferences.

PMID:42313396 | DOI:10.1080/08989621.2026.2691602