Recent advances in cancer neuroscience have established the nervous system as an active regulator of tumor initiation and progression, emphasizing the complex bidirectional crosstalk between neural networks and oncology. In order to deconstruct the relationship between primary central nervous system malignancies and brain metastasis, this review systematically studies the specific mechanisms of neuron tumor synaptic communication, paracrine signaling, and neuroimmune interactions. Innovatively, autophagy is considered as a regulatory bridge connecting neuronal activity and tumor behavior. When functioning in neurons, autophagic flux determines synaptic plasticity and regulates neurotransmitter turnover. Inside tumor cells, autophagy may lead to uncontrolled proliferation and help evade immune surveillance. Integrating these molecular observations establishes the neuro-autophagy-tumor axis, and interconnected nodes in this axis provide emerging therapeutic strategies that target neural signaling and autophagy. These insights highlight the importance of incorporating neurobiological context into cancer research and position autophagy as a promising target for disrupting neural regulation in cancer therapy.

Fucose metabolism and fucosylation are emerging as central regulators of intestinal epithelial integrity, immune homeostasis, host-microbiota interactions, and tumor progression. Increasing evidence implicates dysregulated fucosylation in the pathogenesis of inflammatory bowel disease (IBD), colorectal cancer (CRC), and necrotizing enterocolitis (NEC). Under physiological conditions, fucosylated glycans maintain mucus barrier stability, microbial symbiosis, and mucosal immune tolerance, whereas disrupted fucosylation promotes barrier dysfunction, dysbiosis, chronic inflammation, and intestinal carcinogenesis. In IBD, altered fucosylation impairs epithelial repair and immune regulation. In CRC, abnormal fucosylation drives oncogenic signaling, metabolic reprogramming, immune evasion, and metastasis while also providing clinically relevant biomarkers and therapeutic targets. In NEC, epithelial fucosylation and human milk oligosaccharides such as 2'-fucosyllactose protect against intestinal injury by enhancing epithelial regeneration, modulating inflammatory signaling, and regulating gut microbial composition. Collectively, these findings identify fucose metabolism linking epithelial biology, immunity, microbiota dynamics, and cancer progression in intestinal disease, highlighting fucosylation pathways as promising targets for diagnosis and therapy.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy occurring in children and a leading cause of cancer-related mortality, thus there is an urgent need for development of novel therapeutic strategies for high risk B-ALL patients. The significance of IKZF1 gene alterations in B-ALL cases is controversial, as some studies have shown those to be associated with poor prognosis, while others have reported that deletion of exons 4-7 of the IKZF1 gene, which results in generation of IKAROS isoform 6, is related favorable prognosis. For the present study, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 was employed for knockout of the IKZF1 gene and various IKAROS knockout lines were established, which allowed for investigation of precise functions of the gene by comparing four lines with different IKAROS isoform 1 and 6 statuses. The results clearly showed induction of significant differentiation and cell cycle progression in IKAROS isoform 6 knockout clones. Furthermore, knockout of IKAROS isoform 6 resulted in significant upregulation of the expression of IKAROS isoform 1 as well as signal transducer and activator of transcription 5 (STAT5) activity, which are considered to be related to the observed features. Further investigations are warranted to provide greater mechanistic insight regarding IKAROS-mediating pathways, which will lead to development of novel therapy for human B-ALL.

Understanding Human papillomavirus (HPV) oncogenic mechanisms is essential for developing preventive and therapeutic strategies and overcoming therapy resistance in HPV-related cancers. These challenges may arise from the ability of high-risk HPV to subvert host tumor suppressors such as p53 and Rb, and to drive oncogenesis through homologous recombination deficiency (HRD) and multi-network dysregulation. Mechanistically, HPV exerts context-dependent effects on the host DNA damage response (DDR). During episomal replication, E6/E7 activate DDR and recruit BRCA1/RAD51 to replication foci to support viral replication without significantly compromising host HR repair. Upon viral integration, however, sustained E6/E7 expression drives HRD and shifts DNA repair toward error-prone end joining, generating genomic instability that fuels malignant transformation. These alterations are most clearly established in cervical cancer, whereas evidence in HPV-positive non-cervical cancer is more variable and requires further context-specific validation. In parallel, HPV E6/E7 antagonize transforming growth factor-β (TGF-β)-mediated tumor suppression and, potentially through FAT Atypical Cadherin 4 (FAT4) down-regulation, engage Wnt/β-catenin signaling. The resultant elevation of nuclear β-catenin induces programmed death-ligand 1 (PD-L1) expression promotes immune evasion, stemness, and invasiveness. Of note, while the DDR-TGF-β-β-catenin-PD-L1 axis is backed by substantial evidence in HPV-related cancers, certain connections within this pathway are extrapolated from non-HPV models or general pathway biology and are explicitly denoted as such in the main text. With residual p53 activity, HRD may confer initial sensitivity to DNA-damaging agents, but resistance frequently develops-a pattern reminiscent of the initial response followed by acquired resistance observed with immunotherapies in HPV-related cancers. Integrating these mechanistic insights, we propose ablative therapies (e.g., ablation, photodynamic therapy, surgery) for cervical intraepithelial neoplasia (CIN), and for advanced or resistant disease, a synthetic-lethality framework combining genotoxic therapies with DDR inhibitors, targeting DDR-TGF-β-β-catenin-PD-L1 axis, and antiviral approaches. The proposed therapeutic strategies, however, should be interpreted with caution, as their evidence base varies across tumor types and warrants further investigation.

A previous systematic review reported that general mental health and anxiety symptoms, but not depression or stress, worsened more for females or women than for males or men from before to during the COVID-19 pandemic based on 12 studies published up to August 2021.

To update a systematic review on sex or gender differences in mental health symptom changes from before to during the COVID-19 pandemic.

Medline, PsycINFO, CINAHL, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, medRxiv, and Open Science Framework Preprints were searched from December 31, 2019, to August 31, 2023.

Eligible studies included data to calculate changes in general mental health, anxiety symptoms, depression symptoms, or stress from before to during the COVID-19 pandemic by sex or gender.

Standardized mean differences (SMDs) for continuous changes and proportions for dichotomous changes were used. Two independent reviewers extracted data and evaluated risk of bias. Data were pooled via random-effects models on March 21, 2024.

The main outcome was the differences in SMD changes and proportions between women or females and men or males of mental health symptoms from before the COVID-19 pandemic to during the COVID-19 pandemic.

The study included 27 unique cohorts from 14 countries (n = 102-18 127; 31 155 women or females and 30 737 men or males). Differences in SMD change between men and women were minimal and not statistically significant for continuous outcomes of general mental health (0.01 [95% CI, -0.07 to 0.10 and 95% prediction interval (PI), -0.23 to 0.25]; 8 cohorts; 21 762 participants; heterogeneity [I2] = 81.4%), anxiety (0.09 [95% CI, -0.04 to 0.22 and 95% PI, -0.27 to 0.45]; 7 cohorts; 6039 participants; I2 = 68.7%), depression (0.10 [95% CI, -0.00 to 0.20 and 95% PI, -0.23 to 0.43]; 12 cohorts; 9750 participants; I2 = 65.4%), and stress (-0.08 [95% CI, -0.16 to 0.01 and 95% PI, -0.18 to 0.02]; 8 cohorts; 2994 participants; I2 = 0%). Substantial heterogeneity, high risk of bias, or both were present across analyses. No studies reported changes for gender minority groups (eg, transgender, nonbinary).

In this systematic review and meta-analysis of sex or gender differences in mental health changes from before to during the COVID-19 pandemic, no significant differences were found. However, findings should be interpreted cautiously and may not apply in all settings due to heterogeneity and methodological limitations of included studies.

Childhood and adolescent asthma remains a major public health concern, and obesity may contribute through mechanical and inflammatory pathways. The Body Roundness Index (BRI), derived from waist circumference and height, may better reflect central adiposity than general body-size measures.

To investigate the association between BRI and asthma in children and adolescents.

A total of 28,789 National Health and Nutrition Examination Survey (NHANES) 1999-2020 participants aged 6-20 years were included. Current asthma was identified using questionnaire data. BRI, calculated from waist circumference and height, was used as the primary exposure. Weighted multivariable logistic regression models were used to examine the association between BRI and current asthma, and restricted cubic spline (RCS) models were applied to assess potential nonlinear associations. Subgroup and sensitivity analyses were performed to assess the robustness of the findings. Weighted receiver operating characteristic (ROC) analyses were used to compare the predictive abilities of BRI and Body Mass Index (BMI) z-score in fully adjusted models.

Higher BRI was associated with higher odds of current asthma (OR = 1.233, 95% CI:1.158-1.313, p < 0.001). RCS analysis suggested a nonlinear association between BRI and current asthma. In fully adjusted analyses, BRI and BMI z score showed comparable discriminative performance, with no significant difference in the area under the curve.

Higher BRI was positively associated with current asthma among children and adolescents. Future prospective studies are warranted to clarify the temporal relationship and underlying biological mechanisms.

The aim of this clinical study was to investigate the effects of functional treatment with twin block (TB) and Herbst appliances on sleep quality.

A total of 46 patients having mandibular retrognathia and identified with OSA were divided randomly into two groups: Twin Block (TB) and Herbst appliances. Changes in sleep parameters (apnoea-hypopnea index (AHI), supine AHI, oxygen desaturation index (ODI), minimum oxygen saturation) at baseline (B/L) and an average of 8-month follow-up (F/U) detected by polygraphy and Pittsburgh Sleep Quality Index (PSQI) were the primary outcomes. Treatment of the mandibular retrognathia was the secondary outcome. Shapiro Wilk test and Q-Q graphs were used to evaluate the distribution of variables according to groups, Mann Whitney U test was used to evaluate the two independent group means of measurements. Paired sample t test was used to evaluate the differences between the B/L and F/U times at p < 0.05 significance level.

Among 46 patients randomized, AHI changed from B/L to F/U in Herbst group statistically significant (1.08 (-0.47-2.63), p = 0.031). While the change from B/L to F/U in the supine AHI was significant in Herbst group (3.29 (-0.20-6.78), 95% (CI), p = 0.001), this value did not reach statistical significance in TB group (0.39 (-0.59-1.37), 95% (CI), p = 0.531). ODI altered from B/L to F/U in Herbst group statistically significant (2.09 (0.58-3.60), p = 0.013). There was no change in minimum oxygen saturation following treatment in all groups (3.81 (-1.38-9.00), p = 0.166; 0.87 (-3.17-4.91), p = 0.680, respectively). The F/U values of SNB, ANB and Wits were statistically significantly higher than the B/L values (95% (CI), p < 0.001) in both groups. The average PSQI values were decreased significantly in both groups following functional treatment (95% (CI), p < 0.05).

Significant improvement was observed in sleep parameters with Herbst appliance. Functional orthodontic treatment was found to be effective for adjunctive treatment for OSA. Changes in skeletal sagittal measurements were significant in all groups.

Characterization of emerging diseases often has to occur when analysts who are in charge of tracking emerging threats have limited time. Topic modeling approaches that require limited analyst input and can be applied on electronic health records (EHR) may provide earlier insights. We applied large language model (LLM) based topic modeling to text from emerging pathogens to discover themes.

EHR notes were extracted from Veterans Affairs (VA) Corporate Data Warehouse. We included up to 200 notes from 5 cohorts including Nationally Notifiable Disease (2005-2007), early COVID-19 cases, and outbreak-related notes from Zika, leptospirosis, COVID-19, and mpox. Notes were sampled from early and late outbreak periods, with a separate cohort that was matched to the early period. Clinical sections were identified using medspaCy to extract tokens from the History of Present Illness (HPI). Topic modeling was conducted using TopicGPT (Mistral-7B-Instruct-0.3), which was modified to perform inferences on local infrastructure to protect sensitive data.

A total of 1,841 clinical documents were processed for this analysis on an NVIDIA A40 GPU. The most frequent topic category surfaced by TopicGPT in each cohort was "Infectious Disease." Expert review on a sample of topics demonstrated a 61.5% appropriate representation of topic and explanation based on the original HPI.

Automated topic modeling methods permit extraction and summary of crucial emerging themes. Still, they would benefit from optimization to provide timely analysis of high-volume documents of emerging diseases. VA data were used to evaluate these capabilities for early risk and exposure detection, but they could also be useful to recognize and monitor for early signal of disease among Service Members.

Upper airway disorders such as vocal cord dysfunction (VCD) may present in a similar manner to asthma. Identifying and differentiating between underlying asthma and VCD may significantly affect treatment options. This study reanalyzed the comprehensive pulmonary function data obtained from the STAMPEDE III study to compare findings in patients diagnosed with either asthma, airway hyperreactivity, and VCD.

The STudy of Active duty Military for Pulmonary Disease Related to Environmental Deployment Exposures (STAMPEDE) III was a prospective, observational study of active duty military with post-deployment exertional dyspnea. All patients underwent spirometry with bronchodilator response, impulse oscillometry (IOS), methacholine challenge testing, and exercise laryngoscopy. Several diagnostic categories from the STAMPEDE III study included asthma, airway hyperreactivity (AHR), and upper airway disorders. The results of the pulmonary function testing, flow volume loop (FVL), and impulse oscillometry (IOS) were directly compared between the 3 diagnostic groups.

Flow volume loop abnormalities were found in all groups. The forced inspiratory flow at 50% of the vital capacity (FIF50%) was lower in the VCD group at 4.43 ± 1.90 but not significant. Evaluation of the forced expiratory flow to force inspiratory flow (FEF50%/FIF50%) ratio was lower in the asthma group <1.0 and favored expiratory obstruction. Comparison of the FEF50%/FIF50% ratio for those patients with truncated inspiratory FVL (1.29 ± 0.6 vs. 1.19 ± 0.84 vs. 1.34 ± 0.53) also showed no differences. From the IOS data, baseline resistance at 5 Hz (R5% predicted) and resistance at 20 Hz (R20% predicted) values were significantly elevated in the asthma group (177.6 ± 52.5% and 149.3 ± 36.2%, respectively) compared to the VCD group (136.1 ± 48.7% and 126.4 ± 40.4%, respectively), P = .001 and P = .016. R5-R20 values were different in all 3 groups where asthma was the highest (1.44 ± 0.87) vs. VCD (0.81 ± 0.82) vs. AHR (0.49 ± 0.40). A significant difference was also noted with reactance at 5 Hz (X5)where asthma was the lowest (-1.93 ± 0.92) vs. VCD (-1.47 ± 0.77) vs. AHR (-1.07 ± 0.34).

While baseline spirometry and FVL do not readily differentiate asthma and VCD, the findings on IOS suggested differences between these patients. The use of IOS should be incorporated into the evaluation of patients with suspected VCD due to measurements of inspiratory impedance.

There are bidirectional associations between COVID-19 and thyroid disease; little is known about these risks among active-duty service members (ADSM). This study seeks to understand the associations between COVID-19 and thyroid disease in this population and in non-active-duty adults within the military health system.

The researchers conducted a retrospective propensity score-matched cohort study using the Military Health System Database including individuals 18-64 years of age. International Classification of Diseases, 10th revision codes and laboratory results identified COVID-19 infections from July 2020 to June 2021. Patients with COVID-19 were matched 1:2 to controls based on age, sex, beneficiary type, month, and a propensity score. Thyroid disease was identified by ICD-10 codes and those with a thyroid diagnosis in the year prior were excluded. Hazard ratios (HR) and Bonferroni-adjusted 95% confidence intervals (95BoCI) were calculated.

There were 103,778 exposures and 207,556 controls among ADSM and 125,399 exposures and 250,798 controls among non-ADSM. Among ADSM there was a significant association with having any thyroid disease diagnoses (HR = 1.48, 95%CI [1.15-1.89]). However, no significant relationship was found between COVID-19 infection and hypothyroidism (HR = 1.11, 95BoCI [0.93-1.31]), Hashimoto's thyroiditis (HR = 1.07, 95BoCI [0.77-1.48]), Grave's disease (HR = 1.20, 95BoCI [0.85-1.70]), or other thyroiditis (HR = 1.11, 95BoCI [0.83-1.47]). Non-ADSM adults from ages 18-64 showed significantly increased rates of hypothyroidism (HR = 1.11, 95BoCI [1.03-1.19]), Hashimoto's thyroiditis (HR = 1.15, 95BoCI [1.01-1.31]), Grave's disease (HR = 1.26, 95BoCI [1.09-1.46]), and other thyroiditis (HR = 1.31, 95BoCI [1.18-1.45]).

ADSMs with COVID-19 infection demonstrate an increased risk for combined thyroid disease, although non-ADSM adults had significantly increased rates of Grave's disease, Hashimoto's disease, hypothyroidism, and other thyroiditis. These results highlight that even in young, healthy populations like the ADSMs, COVID-19 can lead to long-term thyroid dysfunction.