Publications

Binocular rivalry occurs when incompatible images presented to each eye lead to alternations between two competing percepts. While several visual and multisensory factors can affect binocular rivalry dynamics, whether perceptual transitions themselves can be subject to cross-modal influences remains unknown. We developed a conditioning paradigm to test whether neutral auditory stimuli, when paired with visual probe-induced perceptual switches, could subsequently influence binocular rivalry dynamics. Participants viewed rivaling orthogonally oriented gratings of different colors. During conditioning, auditory stimuli were systematically paired with visual probes that triggered perceptual switches. Following conditioning, the presentation of conditioned sounds alone produced two effects: shorter dominance durations and, critically, faster perceptual switches. Control conditions confirmed that this conditioning effect could not be attributed to auditory stimulation itself, time on task, or report biases. Our findings provide evidence that binocular rivalry dynamics can be shaped by cross-modal associative learning processes, whereby conditioned sounds serve as predictive cues for perceptual transitions, effectively lowering the threshold for switches between competing stimuli. These results offer new insights into how auditory signals might be incorporated into predictive models that influence visual perception during the resolution of visual ambiguities.

BACKGROUND: Alcohol consumption is a significant risk factor for liver cancer, particularly hepatocellular carcinoma. In China, the incidence of liver cancer has been rising, necessitating an in-depth analysis of the relationship between alcohol consumption and liver cancer burden.

OBJECTIVE: This study aims to assess the burden of alcohol-associated liver cancer (A-LC) in China from 1990 to 2021, utilising data from the Global Burden of Disease (GBD) Study 2021.

METHODS: This study first gathered data on A-LC in China, focusing on age, sex, incidence, prevalence, mortality, disability-adjusted life years (DALYs) and risk factors, using information from the 2021 GBD study covering the years 1990-2021. Next, the research examined the temporal trends of A-LC burdens in China during the same period, employing linear regression modeling to calculate estimated annual percentage change (EAPC) values. Additionally, the autoregressive integrated moving average and exponential smoothing model were utilised to project future disease burdens from 2022 to 2050. Finally, the study analysed risk factors associated with A-LC.

RESULTS: The number of deaths and DALYs for A-LC grew significantly during the study period 1990-2021 (in 1990, in 2021). However, age-standardised deaths and DALYs declined (deaths: 0.87 in 1990 and 0.85 in 2021, DALYs: 24.26 in 1990 and 22.01 in 2021). EAPC = 0.16 (95% CI 0-0.32) for deaths in patients with A-LC and EAPC = -0.18 (95% CI -0.34 to -0.01) for DALYs. Although age-standardized death rates have declined in the last 3 years, the number of incidence, disease and death cases of A-LC patients in China has increased with the progress of time. In 2021, ASIR and ASPR reached the highest in history and the large base of A-LC patients in China and the overall situation of the people should not be underestimated. While East Asia and the high-income Asia-Pacific region declined over the study period, Central Asia saw an increase in age-standardised DALY rates. Age-standardised DALYs also grew significantly in high-income populations in North America and Australasia.

CONCLUSION: A-LC remains a serious threat to the major health problems of the Chinese people, especially men, and the burden of liver cancer associated with obesity risk factors is also increasing significantly and is expected to continue to grow over the next 25 years.

BACKGROUND: Non-compliance with radiotherapy (RT) is a critical barrier to effective cancer care, particularly in low- and middle-income countries like the Philippines. Despite a high national cancer burden, there is a lack of research on the specific factors driving RT non-compliance within the Philippine public health system. This study aimed to identify the independent predictors of non-compliance at a major public cancer center, to inform targeted interventions.

METHODS: This retrospective cohort study analysed the records of 448 patients with breast, cervical, head and neck, endometrial or rectal cancer who underwent curative intent RT at a large public cancer center in the Philippines between January 2022 and April 2024. Non-compliance was defined as missing two or more scheduled RT sessions. A hierarchical multivariable binary logistic regression model was used to identify independent predictors, assessing sociodemographic, clinical and seasonal/systemic factors in sequential blocks.

RESULTS: The overall non-compliance rate was 42.4%. The final multivariable model revealed that non-compliance was primarily driven by a convergence of clinical and systemic factors rather than patient demographics. The strongest predictors reflected clinical severity, specifically cancer type [cervical: odds ratio (OR) = 7.43; head and neck: OR = 3.54] and the need for a treatment replan (OR = 5.60). Systemic factors were also significant predictors, including an internal referral source (OR = 1.83) and treatment timing. Specifically, the risk of non-compliance increased for patients undergoing computed tomography simulation in the third quarter (July-September) and for those starting treatment in the fourth quarter (October-December), which are periods associated with regional climatic and socioeconomic pressures.

CONCLUSION: In this Philippine public cancer center, RT non-compliance is driven by clinical vulnerability and dynamic systemic pressures, not static patient demographics. These findings highlight the need to shift from passive risk assessment to proactive, risk-stratified interventions. Implementing strategies such as patient navigation and support programs, adjusted for predictable seasonal pressures, can mitigate vulnerability, improve treatment adherence and ultimately enhance cancer outcomes in resource-constrained settings.

BACKGROUND: Cancer anorexia-cachexia syndrome (CACS) is a multifactorial metabolic condition prevalent among patients with advanced malignancies and often exacerbated by chemotherapy or radiotherapy (RT). While pharmacologic options such as megestrol and corticosteroids are available, their use is limited by cost or adverse effects. Olanzapine, a second-generation antipsychotic, has recently been recommended by American Society of Clinical Oncology for managing CACS, but real-world data remain scarce.

METHODS: This retrospective cohort study was conducted at a tertiary oncology centre in West Bengal, India, and included patients aged 18-70 years with any solid malignancy and severe anorexia, receiving chemotherapy, RT or palliative care. All patients were treated with low-dose Olanzapine (2.5 mg/day) for 12 weeks. Data were extracted from medical records for the period between 1 January 2024, and 31 January 2025.

RESULTS: Fifty patients met the inclusion criteria. The median age was 44.5 years and 82% had Stage III/IV disease. Of these, 82% (n = 41/50) reported improvement in anorexia symptoms, 82% maintained or gained weight and 16% (n = 8/50) gained at least 1 kg. Among 24 patients with refractory nausea, 50% reported symptomatic relief. No adverse events attributable to Olanzapine were documented.

CONCLUSION: Low-dose olanzapine (2.5 mg/day) is an effective, well-tolerated and cost-efficient option for the management of cancer-related anorexia and nausea in real-world clinical settings. Its use may be particularly beneficial in resource-limited environments and should be considered as a first-line pharmacologic intervention for CACS. Further prospective studies are warranted.

Opioids remain a central element of perioperative pain management despite increased utilization of multimodal adjuvant strategies intended to reduce their use. Contemporary use of methadone and buprenorphine, both conceived as opioid analgesics, is dominated by their essential roles in the treatment of opioid use disorder. Compared to usual care opioids, however, they provide improved post-operative pain control while reducing analgesic requirements. These findings argue for their expanded role within perioperative multimodal analgesia strategies.

PURPOSE: To investigate the therapeutic potential of Curcuma longa-derived extracellular vesicle-like particles (CL-EVLPs) in a benzalkonium chloride (BAC)-induced corneal injury model.

METHODS: CL-EVLPs were isolated via ultracentrifugation and characterized. A murine dry eye model was induced by topical application of BAC. Corneal injury and repair outcomes were assessed using clinical scoring, histopathology, and proteomic analysis. Western blotting and real-time quantitative polymerase chain reaction were conducted to quantify protein or mRNA levels. Bioinformatics analysis was performed using STRING and Cytoscape software.

RESULTS: CL-EVLPs, with a typical saucer- or cup-shaped structure with a peak diameter of 104 nm and an average diameter of 138.4 ± 64.3 nm, were efficiently taken up by corneal epithelial cells. Treatment with CL-EVLPs significantly accelerated corneal epithelial repair, reduced pathologic neovascularization, promoted corneal nerve regeneration, and suppressed inflammatory responses in a dry eye mouse model. Proteomic analysis revealed that CL-EVLPs are involved mainly in biological processes such as inflammation, oxidative stress, and immune regulation. Mechanistically, CL-EVLPs upregulated the cornea-specific protein keratin 12 but downregulated the hyperproliferation-associated protein Keratin 10. Additionally, we confirmed that key factors such as proangiogenic VEGFA, proteolytic MMP9, the inflammatory mediators IL-1β and S100A8/A9, and the related transcription factor NF-κB were significantly suppressed, whereas the expression levels of the transcription activator Nrf2 increased.

CONCLUSIONS: CL-EVLPs represent a novel natural nanobiologic that restores ocular surface homeostasis, effectively enhancing corneal epithelial regeneration and neural repair in the ocular surface microenvironment. This study provides a foundation for the development of plant-derived EVLPs as a safer and more economical therapeutic strategy for ocular surface disorders.

OBJECTIVE: To investigate whether gradually discontinuing chronic opioid therapy (COT) affects quality of life (QOL), depression, and anxiety.

DESIGN: Double-blinded, randomized controlled trial.

SETTING: Ten primary care clinics in Wisconsin.

PARTICIPANTS: Adults on stable doses of COT for chronic noncancer pain.

INTERVENTIONS: Participants were blinded and randomized to either a slow taper or to continue their COT. Participants were assessed at baseline, 3, 6, 9, and 12 months post-enrollment.

OUTCOME MEASURES: Primary outcomes were study completion and QOL, measured by the Medical Outcomes Study Questionnaire Short Form 36 Health Survey version 2. Secondary outcomes were depression and anxiety symptoms, measured using the Patient Health Questionnaire-9 Depression Scale and the Generalized Anxiety Disorder-7 Anxiety Scale, respectively.

RESULTS: Of the 1,140 patients invited to participate, 18 enrolled-all prescribed tramadol or hydrocodone at the time of enrollment (median morphine milligram equivalents per day [MMED] of 17.5 mg; range: 5-40 MMED). Both groups had similar QOL and depression symptoms. The tapering group reported increased anxiety (p = 0.04).

CONCLUSION: Our findings suggest that opioids can be slowly tapered without affecting QOL or depression. Tapering led to a slight increase in anxiety. Larger-scale studies are needed to confirm our findings.

TRIAL REGISTRATION NUMBER: 21-009836 (ClinicalTrials.gov, Home | ClinicalTrials.gov). The trial was registered on March 22, 2022, "Slow Opioid Tapering Pilot Study of Patients Using Chronic Opioid Therapy."

INTRODUCTION: Prevention of oral overdose of opioids is a critical unmet need. PF614-Multi-Pill Abuse Resistance (MPAR®) was designed to deliver desired opioid-level analgesia at therapeutic dose levels while providing overdose protection if consumed at higher-than-intended doses, through a unique trypsin-activated prodrug approach. PF614, a prodrug of oxycodone, releases oxycodone only after oral ingestion and exposure to trypsin in the small intestine. PF614-MPAR, a combination of PF614 and a potent trypsin inhibitor, nafamostat, will reduce oxycodone release if taken at higher-than-intended doses. The goal of this Phase 1 study was to determine the optimal PF614-nafamostat formulation to optimize the overdose protection that PF614-MPAR should provide.

METHODS: Healthy subjects received oral PF614 25 mg alone or in combination with 10 nafamostat formulations (1-10 mg each), which included immediate-release (IR) solutions, slow or fast extended-release (ER) beads, or a combination of IR/ER nafamostat. Plasma oxycodone concentrations were measured to determine PF614 activation and to identify a nafamostat formulation that would reduce the release of oxycodone only when more than two doses were consumed orally. Once an optimal nafamostat formulation was identified, "PF614-MPAR 25 mg," -overdose protection was evaluated by administering one to eight escalating oral doses to naltrexone-blocked subjects.

RESULTS: The selected PF614 MPAR 25 mg formulation delivered therapeutic oxycodone concentrations equivalent to PF614 alone when administered as one or two doses. However, oxycodone release was suppressed when PF614-MPAR was delivered at 3×, 5×, or 8× doses simultaneously.

CONCLUSION: PF614-MPAR may be the first opioid with both abuse resistance and oral overdose protection.

Drug abuse and misuse have been a public health issue for many years. To curb this problem, abuse-deterrent formulations (ADFs) have been developed. The present research aimed to develop an ADF using a simple yet effective, scalable, and cost-effective technique. The combination of hydrophobic and hydrophilic materials was used to develop the ADF. The hydrophilic drug molecule was coated with a hydrophobic wax material (hydrogenated castor oil-HCO). This hydrophobic coating retards drug extraction and release from the crushed formulation. A hydrophilic polymer, polyethylene oxide (PEO), was included in ADF. It provides mechanical strength to the formulation and deters from physical manipulation. It can also form a gel-like structure by rapid uptake of solvent, which deters -intravenous abuse. In this research, HCO was explored as a hydrophobic material. A 32 full factorial design was utilized to optimize the formulation, in which the quantity of HCO and PEO has a significant impact on the abuse-deterrent features of the formulation. The optimized formulation was tested using a range of real-life conditions. Stability study proves that the prepared formulation is stable at accelerated and long-term conditions for 6 months.