Nevin Manimala

J Immunother. 2026 Jan 9. doi: 10.1097/CJI.0000000000000597. Online ahead of print.

ABSTRACT

DLGAP5 has emerged as a potential biomarker implicated in tumor progression across various cancers, yet its prognostic value in lung cancer remains to be fully elucidated. In this study, we integrated comprehensive bioinformatics analyses with clinical data to investigate the expression patterns of DLGAP5 and its association with patient outcomes in lung cancer. Expression profiling revealed that DLGAP5 levels varied modestly across clinical subgroups defined by age, sex, tumor stage, and grade, with no statistically significant differences observed. Survival analyses demonstrated that elevated DLGAP5 expression was significantly correlated with reduced overall survival, while disease-free survival showed no marked difference. Multivariate Cox regression and clinical prognostic models further confirmed DLGAP5 as an independent risk factor associated with poorer prognosis (HR=2.35, 95% CI: 1.10-5.03, P=0.021). Functional enrichment analyses of differentially expressed genes between the low-DLGAP5 expression group and high-DLGAP5 expression group identified key biological processes and pathways, including transcriptional regulation and cytoskeletal organization, potentially mediating DLGAP5’s role in lung cancer progression. These findings provide robust evidence supporting the prognostic relevance of DLGAP5 in lung cancer and underscore its potential utility as a therapeutic target.

PMID:41508152 | DOI:10.1097/CJI.0000000000000597

Trials. 2026 Jan 8. doi: 10.1186/s13063-026-09424-w. Online ahead of print.

ABSTRACT

BACKGROUND: In clinical trials, eligibility criteria define a population who may benefit from the intervention without incurring undue safety risks. Despite their value, overly stringent eligibility criteria may pose barriers to inclusive recruitment. They may disproportionately exclude groups of people more likely to be diagnosed at later cancer stages, or have specific co-morbidities which can be associated with socio-demographic or ethnic background. The National Institute for Health and Care Research Innovations in Clinical Trial Design and Delivery for the Under-served (NIHR-INCLUDE) guidance highlighted several groups of people who may be underserved by clinical research. The aim of this review was to assess eligibility criteria in bladder and head and neck oncology trials and consider their potential impact on potentially underserved groups.

METHODS: This scoping review included multi-centre, interventional, phase II and III trials in bladder or head and neck cancer, which recruited UK participants between 2013 and 2023. Trials were identified via searches of ClinicalTrials.gov, the International Standard Randomised Controlled Trial Number (ISRCTN) registry, and NIHR Clinical Portfolio Management System (CPMS). Trials’ eligibility criteria were categorised and analysed narratively. Trial parameters (recruitment period, funding type, and whether they were of investigational medicinal products (IMPs)) were cross-tabulated with common exclusion criteria using Fisher’s exact test.

RESULTS: Thirty-eight bladder and 30 head and neck cancer trials met the selection criteria. Twenty-eight out of 68 (41%) had non-commercial sponsors. Fifty-six out of 68 (82%) were of IMPs. Forty-one out of 68 (60%) were industry-funded. Fifty-one out of 68 (75%) were for locally advanced, metastatic, or recurrent disease. Common exclusion criteria relating to pregnancy, performance status, HIV status, and cognitive ability may disproportionately impact some underserved groups suggested by the NIHR-INCLUDE guidance.

CONCLUSIONS: This review highlights common exclusion criteria which may disproportionately exclude underserved groups from UK bladder and head and neck oncology trials. To facilitate accessibility to oncology trials, sponsors and triallists should consider how potentially underrepresented groups may be safely included during development of eligibility criteria.

PMID:41508127 | DOI:10.1186/s13063-026-09424-w

Chin Neurosurg J. 2026 Jan 8;12(1):1. doi: 10.1186/s41016-025-00423-5.

ABSTRACT

BACKGROUND: Secondary decompressive craniectomy (DC) is commonly integrated into tiered therapeutic protocols in the intensive care unit (ICU) to manage elevated intracranial pressure following traumatic brain injury (TBI). Identifying high-risk patients in advance could enable early intervention and help prevent further deterioration. This study aims to develop a machine learning-based predictive model using radiomics to assess the likelihood of secondary DC in TBI patients.

METHODS: A total of 65 patients were enrolled and divided into training and test cohorts through stratified random sampling with a 7:3 ratio. Radiomic features were extracted from pre-evacuation CT data. The most relevant features were identified through importance score computation, and various predictive models were assessed using distinct machine learning algorithms and data sources. Model performance was benchmarked to construct an optimal predictive model.

RESULTS: No statistically significant differences were observed in demographic and clinical characteristics between the DC and non-DC groups. The model based solely on demographic and clinical data did not achieve satisfactory performance, with an AUC below 0.5 in the test cohort. In radiomic modeling, the randomForest model demonstrated consistent performance, achieving an AUC of 0.83 in the test cohort. The multiomic model, which incorporated demographic, clinical, and radiomic features, showed improved predictive performance, with the cforest model achieving an AUC of 0.87 in the training cohort and 0.86 in the test cohort.

CONCLUSION: We developed radiomics-based predictive models to assess the likelihood of progressively refractory intracranial hypertension leading to secondary DC in a selected cohort of TBI patients who had undergone emergent craniotomy for hematoma evacuation with bone flap replacement. The model relying solely on radiomic features extracted from the lesion demonstrated satisfactory performance. When these features were integrated with demographic and clinical data to create a multiomic model, predictive performance further improved. These findings highlight the model’s potential to identify high-risk patients, enabling early intervention to prevent further deterioration.

PMID:41508125 | DOI:10.1186/s41016-025-00423-5

Alzheimers Res Ther. 2026 Jan 8. doi: 10.1186/s13195-025-01950-0. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: The clinical interpretation of Alzheimer’s disease (AD) is frequently complicated by the prevalence of missense variants designated as being of uncertain significance within associated genes. Conventional computational prediction tools often overlook disease-specific pathophysiological contexts and lack pertinence and interpretability. Therefore, the present study aimed to develop a novel, interpretable framework for predicting the pathogenicity of AD missense variants by integrating transcriptomic and proteomic data enrichment patterns with machine learning methods.

METHODS: A cross-sectional variant-level analysis was performed using publicly available databases. Missense variants in APOE, APP, PSEN1, PSEN2, SORL1, and TREM2 reported in AD patients were retrieved from Alzforum and compared with missense variants from individuals without neurological diseases, as cataloged in the gnomAD v2.1.1 non-neuro subset. Variants were annotated with tissue-specific expression, secondary structure, relative solvent accessibility, and other functional features using tools like AlphaFold. Enrichment of specific features was assessed with Fisher’s exact tests with Bonferroni correction for multiple comparisons. Given that PSEN1 showed the strongest enrichment signals, six machine-learning algorithms were trained on PSEN1 variants to distinguish AD-associated variants from gnomAD variants, using a 10 × 5 nested cross-validation scheme. External validation was conducted using PSEN1 missense variants from ClinVar annotated as pathogenic/likely pathogenic or benign/likely benign. Model performance was compared with SIFT and PolyPhen-2, and interpretability was evaluated by feature ablation and SHapley Additive exPlanations analyses.

RESULTS: AD-associated variants exhibited statistically significant enrichment within some transcriptomic or proteomic features, with PSEN1 contributing significantly to the enrichment observed across these features. Random forest and gradient boosting models achieved high performance in the internal training dataset and maintained high recall in the external validation dataset, outperforming SIFT and approaching the performance of PolyPhen-2. Relative solvent accessibility was the most discriminative individual feature, while regional and topological features provided complementary discriminative power.

CONCLUSIONS: This integrative, multi-omics framework links disease-specific enrichment patterns with interpretable gene-level machine learning for AD missense variants. The results highlight the importance of expression level, structural context, etc. for PSEN1 variant pathogenicity and may help prioritize variants for functional studies. Further validation in additional genes and independent cohorts is warranted prior to any clinical application.

PMID:41508098 | DOI:10.1186/s13195-025-01950-0

BMC Sports Sci Med Rehabil. 2026 Jan 8. doi: 10.1186/s13102-025-01505-8. Online ahead of print.

ABSTRACT

BACKGROUND: Lateral ankle sprains (LAS) are among the most common musculoskeletal injuries globally. Although international frameworks such as the Rehabilitation-Oriented Assessment Tool (ROAST) and Ankle-GO provide structured approaches for LAS assessment and return-to-sport (RTS) evaluation, their implementation in Sweden has not been investigated.

METHODS: A cross-sectional online survey was distributed to registered Swedish physiotherapists managing patients with LAS. The survey assessed adherence to the original ROAST, as well as modified versions of the frameworks (ROAST_modified and Ankle-GO_modified). Additionally, physiotherapists’ self-rated confidence in their methods was assessed to explore potential discrepancies between perceived competence and framework adherence. Descriptive and inferential statistics were used to analyse associations between reported assessment practices and physiotherapists’ workplace location, educational level, and clinical experience.

RESULTS: A total of 124 physiotherapists responded. Most (87.1%) reported using fewer than 50% of ROAST criteria, while 48.4% met at least 50% of ROAST_modified criteria. Adherence was significantly higher among those working in urban areas (p = 0.032), with no significant differences based on educational level or years of clinical experience. Regarding RTS, 36.7% of physiotherapists applied methods aligned with Ankle-GO_modified, but only 6.5% regularly used patient-reported outcome measures (PROMs) in this context. The most commonly used assessment domains were gait pattern, range of motion, and muscle strength, while PROMs and physical activity level were rarely included.

CONCLUSIONS: Adherence to international frameworks for LAS assessment was generally low among Swedish physiotherapists, but higher when modified versions were applied. Urban-based physiotherapists reported higher adherence compared to their rural counterparts, while educational level and experience had little influence. A discrepancy between perceived confidence and actual adherence suggests a gap between self-assessed competence and implementation.

PMID:41508095 | DOI:10.1186/s13102-025-01505-8

Zhongguo Zhong Yao Za Zhi. 2025 Nov;50(22):6491-6496. doi: 10.19540/j.cnki.cjcmm.20250724.501.

ABSTRACT

Pien Tze Huang has the efficacy of clearing heat, removing toxins, cooling the blood, removing blood stasis, subduing swelling, and relieving pain. It is widely used in the treatment of acute viral hepatitis, carbuncles and furuncles, unidentified swelling and poison, blunt trauma, and various inflammations. To investigate the clinical efficacy and safety of Pien Tze Huang Capsules combined with Compound Pien Tze Huang Hemorrhoid Ointment in controlling the postoperative inflammatory response of wounds in patients undergoing surgery for mixed hemorrhoids, a multicenter, randomized, open-label, and positive-controlled clinical trial was conducted at 12 tertiary medical institutions in China. A total of 240 patients who underwent Milligan-Morgan hemorrhoidectomy for mixed hemorrhoids were enrolled and randomly assigned to the treatment or control group(1∶1). Both groups received sitz baths with Compound Jingjie for Fumigation and Washing as basic treatment. The treatment group additionally received Pien Tze Huang Capsules orally(2 capsules per dose, 3 times per day) and topical application of Compound Pien Tze Huang Hemorrhoid Ointment(2.5 g, twice per day), while the control group received topical Mayinglong Shexiang Hemorrhoid Ointment(2.5 g, twice per day). The treatment duration was 7 days. Primary efficacy endpoints included wound exudation scores, wound bleeding scores, and wound granulation tissue formation scores, and secondary endpoints included perianal edema scores, pain score using pain visual analogue scale(VAS) scores, postoperative analgesic use, and adverse events. RESULTS:: showed that in the full analysis set(FAS), the wound exudation scores on postoperative day 7 was significantly lower in the treatment group compared to that in the control group(P<0.05). In the per-protocol set(PPS), the wound exudation scores on postoperative days 3 and 7 was also significantly lower in the treatment group(P<0.05). While the treatment group showed lower perianal edema scores and pain VAS scores than the control group, the differences were not statistically significant. No statistically significant differences were observed between the two groups in wound bleeding scores, wound granulation tissue formation scores, analgesic use rate or amount, or incidence of adverse reactions. A total of 56 adverse events were observed, with 25 in the treatment group and 31 in the control group. The incidence of adverse reactions was comparable between groups, with no statistically significant difference. No serious drug-related adverse events were observed in either group. The results suggest that the Pien Tze Huang Capsules combined with Compound Pien Tze Huang Hemorrhoid Ointment can reduce wound exudation after surgery for mixed hemorrhoids, playing a beneficial role in controlling postoperative inflammation. The treatment offers good safety and tolerability, showing great potential as a postoperative adjunctive therapy integrating traditional Chinese medicine and western medicine.

PMID:41508088 | DOI:10.19540/j.cnki.cjcmm.20250724.501

Zhongguo Zhong Yao Za Zhi. 2025 Nov;50(22):6265-6272. doi: 10.19540/j.cnki.cjcmm.20250409.501.

ABSTRACT

Dingkundan has the effect of warming Yang, dispelling cold, activating blood, resolving stasis, and relieving pain. It is used for treating dysmenorrhea, amenorrhea, menopausal disorders, infertility, and postpartum diseases caused by cold coagulation and blood stasis. Dingkundan Pills have some shortcomings, such as inconvenient administration, high sugar content, and slow absorption. Dingkundan Oral Liquid is a new dosage form developed on the basis of the pills, with a good taste, fast absorption, and convenient use, while there is no relevant research now. To evaluate the efficacy and safety of Dingkundan Oral Liquid in the treatment of primary dysmenorrhea with cold coagulation and blood stasis, a randomized controlled, double-blind, and double-simulated clinical trial was conducted. One hundred and eight subjects were randomized into test group, control group, and placebo group at a ratio of 1∶1∶1, with 36 subjects in each group. The test group, control group, and placebo group were treated with Dingkundan Oral Liquid + Ibuprofen Sustained Release Capsules simulator, Ibuprofen Sustained Release Capsules + Dingkundan Oral Liquid simulator, and two drug simulants, respectively. The course of treatment was 3 menstrual cycles. The effectiveness indicators included primary efficacy indicators [visual analogue scale(VAS) score difference], secondary efficacy indicators [total effective rate, COX menstrual symptom scale(CMSS) score difference, traditional Chinese medicine(TCM) syndrome score difference, single symptom disappearance rate, menstrual serum prostaglandin F_(2α)(PGF_(2α)), PGF_(2α)/prostaglandin E_2(PGE_2), thromboxane B_2(TXB_2), 6-keto-prostaglandin-F_(1α)(6-keto-PGF_(1α)), and pulsatility index(PI) and resistance index(RI) of uterine artery flow]. Safety was evaluated based on clinical adverse reactions/events, vital signs, and laboratory tests. The results of the clinical trial showed that after 3 menstrual cycles of treatment, VAS scores difference of the three groups had statistically significant differences, and test group and control group demonstrated significantly better therapeutic effects than placebo group. Full analysis set(FAS) of the difference between the two groups was 0.33, 95%CI[-0.19, 0.86], and per-protocol set(PPS) was 0.35, 95%CI[-0.27, 0.97]. The non-inferiority test was valid. There were statistically significant differences in total response rate, CMSS score difference, efficacy regarding TCM symptoms difference, single symptom disappearance rates, serum or plasma levels of PGF_(2α), PGF_(2α)/PGE_2, TXB_2, and 6-keto-PGF_(1α), and PI and RI of uterine artery flow among the 3 groups. In terms of safety, no adverse reactions were observed in the 3 groups, and no obvious abnormalities were observed in liver and kidney function or electrocardiogram. According to the results, Dingkundan Oral Liquid is effective in the treatment of primary dysmenorrhea with cold coagulation and blood stasis, and its therapeutic effect is not inferior to that of Ibuprofen Sustained Release Capsules commonly used in clinical practice. Moreover, Dingkundan Oral Liquid has better therapeutic effects on TCM symptoms and accompanying symptoms of dysmenorrhea, with more stable long-term curative effect, demonstrating a clinical promotion and application value.

PMID:41508064 | DOI:10.19540/j.cnki.cjcmm.20250409.501

Res Integr Peer Rev. 2026 Jan 9;11(1):1. doi: 10.1186/s41073-025-00185-9.

ABSTRACT

BACKGROUND: While conducting an umbrella review of e-cigarettes for smoking cessation, we observed that in many instances, systematic review authors reported findings favorable to the treatment, yet they declined to recommend it or recommended against it despite the evidence of its effectiveness in their own systematic reviews.

EXISTING LITERATURE: We searched the literature for a term or category to describe this form of reporting bias where the authors’ recommendations dismiss their findings of treatment benefit. Ideally the term spin bias should apply to any conclusion or recommendation not supported by the findings of the study, but in practice spin bias is almost exclusively applied to the narrative attribution of significance or causation to statistically non-significant data or findings.

ISSUE UNDER DISCUSSION: After observing that many systematic review authors dismissed their findings of effectiveness for e-cigarettes for cessation, we wondered if this form of reporting bias also occurs in the systematic reviews on other controversial treatments. We made a rapid search for recent systematic reviews on medical cannabis for pain, another controversial treatment. Here also we observed that many authors did not recommend cannabis for pain management even though their findings clearly showed treatment benefit. We tentatively offer the term reverse spin bias for the narrative discounting or dismissal of statistically significant findings. We catalogued the narrative turns that enabled reverse spin bias in 20 systematic reviews of e-cigarettes for cessation and medical cannabis for pain. We identified five mechanisms: discount the evidence base, discredit the primary studies, appeal to fear, dismiss the treatment modality a priori, and omit findings. We speculate that authors introduce reverse spin bias to improve their chances for publication or to support their position about a treatment.

CONCLUSION: A standard task for editors and peer reviewers is confirming that treatment recommendations are supported by the review’s data, yet our examples strongly suggest that this examination for reporting bias is frequently skipped. By proposing a new term, reverse spin bias, we hope to bring stronger scrutiny to bear on these instances of reporting bias that are detrimental to evidence-informed clinical practice.

PMID:41508049 | DOI:10.1186/s41073-025-00185-9

Diabet Med. 2026 Jan 8:e70207. doi: 10.1111/dme.70207. Online ahead of print.

ABSTRACT

AIMS: The objective of this study was to evaluate the Diabetes Eating Problems Survey-Revised (DEPS-R) against the Eating Disorder Diagnostic Interview (EDDI). Specific aims were to (1) assess the ability of the DEPS-R to identify Diagnostic and Statistical Manual-5 (DSM-5) eating disorders, including sensitivity and specificity of the current DEPS-R cutoff ≥20 and (2) report the correlation of each item to the presence of any eating disorder.

METHODS: Baseline data from 293 women (14-35 years) with type 1 diabetes (T1D) and body image concerns enrolled in a multinational randomized controlled trial were examined. Receiver operating characteristic (ROC) analysis, univariate logistic regression and two-sample t-test were performed.

RESULTS: The ROC analysis demonstrated good accuracy of the DEPS-R with an area under the curve (AUC) of 0.82 (95% CI 0.79-0.94). The cutoff of ≥20 yielded a sensitivity of 87.5% (95% CI 83.6%-91.3%) and a specificity of 60.4% (95% CI 54.8%-66.0%). Univariate logistic regression identified 12 items as significantly correlated with the presence of any eating disorder. The highest odds ratios (OR) were observed for items 9 (OR = 3.64), 8 (OR = 2.85), 13 (OR = 2.36), 14 (OR = 2.23), 15 (OR = 1.99) and 5 (OR = 1.99).

CONCLUSIONS: This is the first study to investigate the ability of the DEPS-R to identify DSM-5 eating disorder diagnosis established via a diagnostic interview using a ROC-analysis. DEPS-R cutoff ≥20 correctly identified most cases with eating disorders but showed moderate specificity, considered acceptable as an initial screening tool for disordered eating. In clinical care, specific DEPS-R items may be emphasized to explore the presence of disordered eating behaviours and eating disorders.

PMID:41508045 | DOI:10.1111/dme.70207

Head Face Med. 2026 Jan 8. doi: 10.1186/s13005-025-00577-8. Online ahead of print.

ABSTRACT

BACKGROUND: Extensive retraction of mandibular incisors in Class III treatment may increase the risk of orthodontically induced apical root resorption (OIARR). This retrospective cohort study aimed to assess the incidence and severity of OIARR in Class III patients treated nonsurgically with lingual high precision fixed appliances (HPFAs) and significant anterior tooth retraction.

METHODS: Eligible for inclusion were adolescent and adult Class III patients treated with lingual HPFAs (WIN, DW Lingual Systems GmbH) and extraction of lower premolars, who completed treatment between 2015 and 2024. Pre- (T0) and post-treatment (T1) panoramic radiographs were measured for root and crown lengths, with relative root resorption (rRR, %) calculated for each tooth. Clinically relevant OIARR was assessed using the Malmgren index (scores 1-4). Statistical significance of mean rRR (%) changes was assessed using one-sample t-tests (α = 0.05).

RESULTS: A total of 25 patients (mean age at T1 26.8 ± 9.7 years; 12 females, 13 males; mean Wits at T0 -6.7 ± 2.5 mm) and 350 mandibular teeth were analyzed. The mean rRR for anterior teeth was 3.15 ± 4.05%, with no cases of severe resorption (Malmgren score 4) and only 6.7% of roots exhibiting clinically relevant shortening (Malmgren score 3). There was no increased risk of OIARR in anterior teeth compared to premolars and molars (3.15% vs. 3.31%).

CONCLUSION: Extensive bodily retraction of lower anterior teeth was not associated with significant OIARR in this Class III cohort. Excellent torque control using HPFAs enabled considerable retraction with low risk of OIARR, supporting this approach as a safe nonsurgical alternative for Class III camouflage.

PMID:41508036 | DOI:10.1186/s13005-025-00577-8