A network model of depressive and anxiety symptoms: a statistical evaluation.

BACKGROUND: Although network analysis studies of psychiatric syndromes have increased in recent years, most have emphasized centrality symptoms and robust edges. Broadening the focus to include bridge symptoms within a systematic review could help to elucidate symptoms having the strongest links in network models of psychiatric syndromes. We conducted this systematic review and statistical evaluation of network analyses on depressive and anxiety symptoms to identify the most central symptoms and bridge symptoms, as well as the most robust edge indices of networks. METHODS: A systematic literature search was performed in PubMed, PsycINFO, Web of Science, and EMBASE databases from their inception to May 25, 2022. To determine the most influential symptoms and connections, we analyzed centrality and bridge centrality rankings and aggregated the most robust symptom connections into a summary network. After determining the most central symptoms and bridge symptoms across network models, heterogeneity across studies was examined using linear logistic regression. RESULTS: Thirty-three studies with 78,721 participants were included in this systematic review. Seventeen studies with 23 cross-sectional networks based on the Patient Health Questionnaire (PHQ) and Generalized Anxiety Disorder (GAD-7) assessments of clinical and community samples were examined using centrality scores. Twelve cross-sectional networks based on the PHQ and GAD-7 assessments were examined using bridge centrality scores. We found substantial variability between study samples and network features. 'Sad mood', 'Uncontrollable worry', and 'Worrying too much' were the most central symptoms, while 'Sad mood', 'Restlessness', and 'Motor disturbance' were the most frequent bridge centrality symptoms. In addition, the connection between 'Sleep' and 'Fatigue' was the most frequent edge for the depressive and anxiety symptoms network model. CONCLUSION: Central symptoms, bridge symptoms and robust edges identified in this systematic review can be viewed as potential intervention targets. We also identified gaps in the literature and future directions for network analysis of comorbid depression and anxiety.

The prevalence of poor sleep quality in the general population in China: a meta-analysis of epidemiological studies.

BACKGROUND: The high prevalence of poor sleep quality (PSQ) in the general population leads to negative health outcomes. Since estimates of PSQ prevalence in the Chinese general population vary widely, this meta-analysis aimed to refine these estimates and to identify moderating factors. METHODS: A comprehensive literature search was undertaken in both international (PubMed, PsycINFO, Web of Science, and EMBASE) and Chinese (Wanfang, and the China National Knowledge Infrastructure databases) databases from inception to 23 November 2023. Studies were required to have used standard scales such as the Chinese version of the Pittsburgh Sleep Quality Index (PSQI). The pooled prevalence of PSQ and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup and meta-regression analyses were performed to identify sources of heterogeneity. RESULTS: In 32 studies with a combined 376,824 participants, the pooled prevalence of PSQ was 19.0% (95% CI 15.8-22.8%; range 6.6-43.6%). Across 22 studies that reported PSQI data, the pooled mean score was 4.32 (95%CI 3.82-4.81; SD = 0.502). The pooled mean sleep duration across 8 studies was 7.62 (95% CI 7.23-8.00; SD = 0.194) hours. Subgroup analyses showed that lower education (Q = 4.12, P = 0.042), living in less developed regions (Q = 60.28, P < 0.001), and lower PSQI cutoff values (Q = 9.80, P = 0.007) were significantly associated with PSQ. Meta-regression analyses showed that study quality was inversely associated with estimated PSQ prevalence (ß = - 0.442, P = 0.004). LIMITATIONS: Although measures such as subgroup and meta-regression analyses were performed, substantial heterogeneity remained. Information related to sleep quality, such as comorbid physical diseases or psychiatric disorders, substance use, occupational types, and employment status, were not reported in most studies. CONCLUSION: One in five people in the general population of China may have PSQ and people with lower education or living in western regions may be more susceptible.

Pain trajectories and their associations with cognition among older adults: a 10-year cohort study from network perspective.

BACKGROUND: Few studies have examined the associations between pain trajectories and cognitive function in older adults. This study explored the associations between pain trajectories and different cognitive domains in older adults from a network perspective. METHODS: Data on pain trajectories were derived from the Health and Retirement Study between 2010 and 2020 using latent class growth analyses. Measurements of key cognition domains, including memory, attention, calculation, orientation and language, were included. Linear regression and network analysis were performed to evaluate the associations between different pain trajectories and cognition. RESULTS: A total of 9,551 older adults were included in this study and three trajectories of pain were identified. After controlling for the covariates, persistent severe pain trajectory was associated with poorer overall cognition, memory and calculation ability when compared to mild or non-persistent pain trajectory. In the pain and cognition network model, memory (expected influence (EI) = 0.62), language (EI = 0.58) and calculation (EI = 0.41) were the most central domains. CONCLUSIONS: Pain trajectories appeared stable over time among older adults in this study. Severity of persistent pain was an important risk factor for poor cognition, especially in relation to memory and calculation domains. Interventions targeting memory, language and calculation domains might be useful in addressing cognitive decline in older adults with persistent pain.

Where should "Humans" be in "One Health"? Lessons from COVID-19 for One Health.

The culling of animals that are infected, or suspected to be infected, with COVID-19 has fuelled outcry. What might have contributed to the ongoing debates and discussions about animal rights protection amid global health crises is the lack of a unified understanding and internationally agreed-upon definition of "One Health". The term One Health is often utilised to describe the imperative to protect the health of humans, animals, and plants, along with the overarching ecosystem in an increasingly connected and globalized world. However, to date, there is a dearth of research on how to balance public health decisions that could impact all key stakeholders under the umbrella of One Health, particularly in contexts where human suffering has been immense. To shed light on the issue, this paper discusses whether One Health means "human-centred connected health" in a largely human-dominated planet, particularly amid crises like COVID-19. The insights of this study could help policymakers make more informed decisions that could effectively and efficiently protect human health while balancing the health and well-being of the rest of the inhabitants of our shared planet Earth.

COVID-19 and Sleep Problems: A Perspective from Bibliometric Analysis.

OBJECTIVES: The Coronavirus Disease 2019 (COVID-19) pandemic and the containment measures for COVID-19 have affected sleep quality in the population. This study explored sleep-related research from a bibliometric perspective to provide an overview of the research outputs in this field. METHODS: Original and review articles were retrieved from the Web of Science Core Collection (WOSCC) database from December 2019 to 7 Aug 2023. R package "bibliometrix" was used to summarize the number of articles of authors, institutions, and countries; count the citations of the articles, and generate a Three-Fields Plot. VOSviewer software was applied to visualize the collaboration network among authors and institutions, and to conduct a co-occurrence analysis of keywords. RESULTS: A total of 4,499 articles on COVID-19 and sleep, and 25,883 articles on non-COVID-19 and sleep were included. Sleep related articles were mainly published by authors from China, the USA, and Italy. For COVID-19 and sleep research, Huazhong University of Science was the most productive institution. The Psychiatry Research was the most influential journal across the different subject categories of this field. "Mental health", "anxiety", and "depression" were the most common keywords, while "sleep quality" and "quality of life" were the likely topic areas in terms of future research directions. CONCLUSIONS: Our findings provide a comprehensive perspective for researchers to understand the wider landscape of both COVID-19 and non-COVID-19 sleep-related research area.

Real-Time Evaluation of Adhesion Processes and Glucose Response of Cancer Cells onto Phenylboronic Acid-Functionalized Films Monitored by Quartz Crystal Microbalance with Dissipation.

Understanding the interactions between cancer cells and smart substrates is of great benefit to physiology and pathology. Herein, we successfully fabricated two phenylboronic acid (PBA)-functionalized films with different surface topographies using a PBA homopolymer (PBAH) and self-assembled nanoparticles (PBAS) via a layer-by-layer assembly technique. We used a quartz crystal microbalance with dissipation (QCM-D) to monitor the entire cell adhesion process and figured out the adhesion kinetics of HepG2 cells on the two PBA-functionalized films. As seen from the QCM-D data, the HepG2 cells displayed distinctly different adhesion behaviors on the two PBA-functionalized films (PBAS and PBAH films). The results showed that the PBAS film promoted cell adhesion and cell spreading owing to its specific physicochemical properties. Likewise, the slope changes in the D-f plots clearly revealed the evolution of the cell adhesion process, which could be classified into three stages during cell adhesion on the PBA-functionalized films. In addition, compared with the PBAH film, the PBAS film could also control cell detachment behavior in the presence of glucose based on the molecular recognition between the PBA group and the cell membrane. Such a glucose-responsive PBAS film is promising for biological applications, including cell-based diagnostics and tissue engineering. In addition, the QCM-D proved to be a useful tool for in situ and real-time monitoring and analysis of interactions between cells and surfaces of supporting substrates.

Post-pandemic policy imperatives to stem violence against women in China.

Violence against women is rampant in China. Even though meaningful strides have been made in the country, it remains disturbingly common for men to assault women-verbally or physically, who may or may not be their partners-in broad daylight in China. To make the situation worse, COVID-19, along with its restrictions, has both undermined women's ability to escape from abuse or violence and society's ability to provide timely help to victims. In light of the rising violence against women post-COVID, in this paper, we discuss the policy imperatives for countries like China to establish effective guardrails and support systems to protect women from the dehumanizing and destabilizing crime that is violence against women-a social malaise that not only harms and undermines the safety of society's daughters, mothers, and grandmothers, but also the integrity of local communities and social contract, let along shared humanity and global solidarity at large.

Prevalence of insomnia and its association with quality of life in caregivers of psychiatric inpatients during the COVID-19 pandemic: a network analysis.

BACKGROUND: Studies on sleep problems among caregivers of psychiatric patients, especially during the COVID-19 pandemic, are limited. This study examined the prevalence and correlates of insomnia symptoms (insomnia hereafter) among caregivers of psychiatric inpatients during the COVID-19 pandemic as well as the association with quality of life (QoL) from a network analysis perspective. METHODS: A multi-center cross-sectional study was conducted on caregivers of inpatients across seven tertiary psychiatric hospitals and psychiatric units of general hospitals. Network analysis explored the structure of insomnia using the R program. The centrality index of "Expected influence" was used to identify central symptoms in the network, and the "flow" function was adopted to identify specific symptoms that were directly associated with QoL. RESULTS: A total of 1,101 caregivers were included. The overall prevalence of insomnia was 18.9% (n = 208; 95% CI = 16.7-21.3%). Severe depressive (OR = 1.185; P < 0.001) and anxiety symptoms (OR = 1.099; P = 0.003), and severe fatigue (OR = 1.320; P < 0.001) were associated with more severe insomnia. The most central nodes included ISI2 ("Sleep maintenance"), ISI7 ("Distress caused by the sleep difficulties") and ISI1 ("Severity of sleep onset"), while "Sleep dissatisfaction" (ISI4), "Distress caused by the sleep difficulties" (ISI7) and "Interference with daytime functioning" (ISI5) had the strongest negative associations with QoL. CONCLUSION: The insomnia prevalence was high among caregivers of psychiatric inpatients during the COVID-19 pandemic, particularly in those with depression, anxiety and fatigue. Considering the negative impact of insomnia on QoL, effective interventions that address insomnia and alteration of sleep dissatisfaction should be developed.

Hikikomori: A perspective from bibliometric analysis.

AIMS: Hikikomori is a common phenomenon reported in Japan and many other countries. However, the broad trends of the research publications on hikikomori are unclear. Therefore, this study examined the patterns of research on hikikomori using bibliometric analysis. METHODS: Relevant publications were searched in Web of Science. Bibliometric analyses were performed with CiteSpace, R and VOSviewer. RESULTS: In total, 297 publications on hikikomori met the eligibility criteria. The International Journal of Social Psychiatry (IF = 10.461) published the most papers (K = 17, or 5.7%) on hikikomori. Takahiro A. Kato from Kyushu University (41; 13.8%; H-index = 18) was the most influential author, while Takahiro A. Kato (total link strength [TLS]: 235), Alan R. Teo (TLS: 157), and Masaru Tateno (TLS: 153) separately had the strongest research collaboration with other researchers. Of all countries that published on hikikomori, Japan had the highest number of publications (K = 91). The keywords "United States" and "psychiatric diagnosis" received the most attention between 2013 and 2015, whereas "health" and "autism spectrum disorder" received the most attention in 2021 and 2022. CONCLUSIONS: Peer-reviewed research publications on hikikomori are growing rapidly and the research trends in this field are also changing.

The digital divide impacts on mental health during the COVID-19 pandemic.

One of the most daunting unintended consequences of the digital revolution is the digital divide (DD), a pervasive social and information inequality. It negatively affects all sectors of society, and exerts compounding influences on other social inequities. To further complicate the situation, the COVID-19 pandemic has been intensifying the scale of DD and deepening the scope of DD barriers with the increasing but imbalanced applications of digital technologies. For instance, while digital technologies can provide support to fulfill people's mental health needs, recurring evidence shows that DD-prone people are more likely to be excluded from critical services, activities, and resources to support their health concerns and challenges. So far, studies about the mental health consequences of DD amid COVID-19 are limited. Available evidence suggests that the general mental health impacts of COVID-19 include anxiety, depression, and suicidal behaviors, while the mental health consequences of DD due to COVID-19 are mainly stress, distress, and anxiety. To shed light on the research gap, based on the social inequality roots of DD and the nexus between DD barriers and factors of social inequalities, this study highlights the alarming overlap between DD-prone communities and vulnerable populations. Furthermore, we underscore the future research directions that could help society better serve both underserved communities.

Mind the "worry fatigue" amid Omicron scares.

In addition to worry, the accumulated unknowns and uncertainties about COVID-19 may also result in "worry fatigue" that could harm the public's vigilance towards the pandemic and their adherence to preventive measures. Worry could be understood as future-oriented concerns and challenges that could result in negative outcomes, whereas worry fatigue is the feeling of extreme burden and burnout associated with too much worry unsolved. As the world embraces its second COVID-19 winter, along with the pandemic-compromised holiday season, the Omicron variant has been declared a variant of concern by the World Health Organization. However, the fluid and unpredictable nature of COVID-19 variants dictates that, instead of definitive answers that could ease people's worry about Omicron, dividing debates and distracting discussions that could further exacerbate people's worry fatigue might be the norm in the coming months. This means that, amid the ever-changing public health guidance, the forever-breaking news reports, and the always-debatable media analyses, government and health officials need to be more invested in addressing people's potential worry and worry fatigue about the pandemic, to ensure the public's rigorous cooperation and compliance with safety measures.

Public health crises and Ukrainian refugees.

Conflicts are inevitable, and so are refugees. Due to conflicts in Ukraine, the global refugee population has reached new highs. As people continue to flee Ukraine amid the ongoing pandemic in droves, their exposure to COVID-19 and infectious diseases that are common among the refugee population, such as tuberculosis, is on the rise as well. Also factoring in the fact that Ukraine has a large population living with communicable diseases like HIV and hepatitis C, along with other non-communicable conditions like diabetes and cancer, there is a pronounced need to protect these refugees and local residents from potential public health crises. In this paper, we investigate the challenges that health and government officials face in addressing refugees' health needs and preferences. Furthermore, we discuss the imperative to provide timely and effective health services to refugees, such as psychoneuroimmunology-based interventions that could help address refugees' multifactorial and multifaceted health needs and requirements. While conflicts are inevitable, public health crises are not. In light of the renewed imperative to safeguard shared humanity and solidify global solidarity, collaborative actions are needed to ensure fair, kind, and true public health environments are available to refugees of the current conflict and beyond.

Psychoneuroimmunology concerns of the Olympic boycotts.

Just weeks away from the Opening Ceremony of the Beijing 2022 Winter Olympics, the United States, followed by Australia, the United Kingdom, and Canada, has declared a diplomatic boycott of the Games. A diplomatic boycott stipulates that while government officials of these countries will not attend the event, the athletes' scheduled attendance will largely remain intact. An unintended consequence of the boycotts is that they force the attending athletes to cope with the stress and distress associated with the 2022 Winter Olympics in an unfamiliar environment on their own. It is important to underscore that many of the challenges the athletes could face amid the Games are either deep-rooted or unprecedented, ranging from stressors fuelled by the nonstop media reports, the competitions, to the Omicron scares. These insights combined, in turn, underscore the imperative for effective and preemptive mental health support for Olympic athletes. To shed light on the issue, this paper highlights the reasons why timely solutions are needed to adequately safeguard Olympic athletes' mental health and overall wellbeing, and underlines promising technology-based solutions that can be cost-effectively designed and developed for the athletes.

Polydopamine-Based Nanoparticles for an Antibiofilm Platform: Influence of Size and Surface Charge on Their Penetration and Accumulation in S. aureus Biofilms.

Various functional polydopamine (PDA) nanoparticles have been developed to treat biofilms in recent years; however, in-depth knowledge of how the physicochemical properties of the nanoparticles impact their penetration and accumulation in biofilms is lacking. In this work, PDA nanoparticles of 15, 60, 90, and 200 nm sizes were synthesized and carboxyl, methoxy, and amine groups were introduced to the particle surface to control their surface charges, and then the penetration and accumulation of these PDA nanoparticles in S. aureus biofilms were investigated. The PDA nanoparticles of approximately 60 nm size (PDA60) showed higher penetration and accumulation abilities than nanoparticles of other sizes, and the positively charged amine groups introduced onto the surfaces of PDA60 nanoparticles were more effective than carboxyl or methoxy groups in promoting the interactions of the nanoparticles with the biofilm. The PDA60 nanoparticles with amine surface groups exhibited good photothermal properties, and confocal laser scanning microscopy revealed that they were able to accumulate in the biofilm in significant amounts, which upon irradiation with a laser of 808 nm wavelength showed a high bactericidal rate (97.1%) against the biofilm. The findings of this work provide guidance for the design and development of nanoparticles for antibiofilm application.

Distribution of an antioxidant in polypropylene/ethylene-octene copolymer blends studied by atomic force microscopy-infrared.

In this work, the microscopic distribution of antioxidant 1010 (AT1010) in blends of isotactic polypropylene (iPP) with an ethylene-octene copolymer (POE) was investigated in situ using the atomic force microscopy-infrared (AFM-IR) technique. Pellets of an iPP/POE blend containing AT1010 at a mass ratio of 79.5 : 20 : 0.5 were extruded at different screw speeds, and were then injection-molded into plates. The domain size of the POE disperse phase in the pellets was about 1 µm, regardless of the screw speed, and remained unchanged in the injection molding. AFM-IR analyses revealed that AT1010 preferred to stay in the POE disperse phase rather than in the iPP matrix, with a concentration ratio of ∼1.2 in the extruded pellets independent of the screw speed, which was further increased to ∼1.5 in the molded plates. The preferred concentration of AT1010 in the POE was in line with its higher solubility in rubber than in iPP, and the enhanced partition of AT1010 in the molded plates was attributed to a longer processing time in the molten state than that for the extruded pellets, which was verified by AFM-IR analyses of pellets extruded with different residence times.

Worldwide prevalence of mild cognitive impairment among community dwellers aged 50 years and older: a meta-analysis and systematic review of epidemiology studies.

BACKGROUND: Mild cognitive impairment (MCI) is the preclinical and transitional stage between healthy ageing and dementia that may be a potential 'target' for interventions designed to delay progression to dementia. In this systematic review and meta-analysis, we assessed the prevalence of MCI worldwide in community-dwelling adults aged 50 years and older. METHODS: PubMed, Web of Science, Embase and PsycINFO database searches were conducted from their respective inception dates to 1 September 2021. Data on the overall prevalence of MCI were synthesised using random effects models. RESULTS: A total of 66 articles covering 242,804 participants fulfilled study criteria for inclusion. The overall prevalence of MCI was 15.56% (95%CI: 13.24-18.03%). Prevalence rates of amnestic MCI and non-amnestic MCI were 10.03% (95%CI: 7.98-12.27%) and 8.72% (95%CI: 6.78-10.89%), respectively. The prevalence of MCI increased with age and decreased with education level. Subgroup and meta-regression analyses revealed that region of study site and male gender proportion per sample were significant correlates of MCI prevalence. CONCLUSION: The global prevalence of MCI among community dwellers is over 15% and is affected by age, gender, education level and region of study sites. Assessment and interventions targeting MCI within at-risk population subgroups should be considered toward the prevention of dementia.

Facial recognition law in China.

Although the prevalence of facial recognition-based COVID-19 surveillance tools and techniques, China does not have a facial recognition law to protect its residents' facial data. Oftentimes, neither the public nor the government knows where people's facial images are stored, how they have been used, who might use or misuse them, and to what extent. This reality is alarming, particularly factoring in the wide range of unintended consequences already caused by good-intentioned measures and mandates amid the pandemic. Biometric data are matters of personal rights and national security. In light of worrisome technologies such as deep-fake pornography, the protection of biometric data is also central to the protection of the dignity of the citizens and the government, if not the industry as well. This paper discusses the urgent need for the Chinese government to establish rigorous and timely facial recognition laws to protect the public's privacy, security, and dignity amid COVID-19 and beyond.

6G and Artificial Intelligence Technologies for Dementia Care: Literature Review and Practical Analysis.

BACKGROUND: The dementia epidemic is progressing fast. As the world's older population keeps skyrocketing, the traditional incompetent, time-consuming, and laborious interventions are becoming increasingly insufficient to address dementia patients' health care needs. This is particularly true amid COVID-19. Instead, efficient, cost-effective, and technology-based strategies, such as sixth-generation communication solutions (6G) and artificial intelligence (AI)-empowered health solutions, might be the key to successfully managing the dementia epidemic until a cure becomes available. However, while 6G and AI technologies hold great promise, no research has examined how 6G and AI applications can effectively and efficiently address dementia patients' health care needs and improve their quality of life. OBJECTIVE: This study aims to investigate ways in which 6G and AI technologies could elevate dementia care to address this study gap. METHODS: A literature review was conducted in databases such as PubMed, Scopus, and PsycINFO. The search focused on three themes: dementia, 6G, and AI technologies. The initial search was conducted on April 25, 2021, complemented by relevant articles identified via a follow-up search on November 11, 2021, and Google Scholar alerts. RESULTS: The findings of the study were analyzed in terms of the interplay between people with dementia's unique health challenges and the promising capabilities of health technologies, with in-depth and comprehensive analyses of advanced technology-based solutions that could address key dementia care needs, ranging from impairments in memory (eg, Egocentric Live 4D Perception), speech (eg, Project Relate), motor (eg, Avatar Robot Café), cognitive (eg, Affectiva), to social interactions (eg, social robots). CONCLUSIONS: To live is to grow old. Yet dementia is neither a proper way to live nor a natural aging process. By identifying advanced health solutions powered by 6G and AI opportunities, our study sheds light on the imperative of leveraging the potential of advanced technologies to elevate dementia patients' will to live, enrich their daily activities, and help them engage in societies across shapes and forms.

Gender inequality and health disparity amid COVID-19.

Gender inequalities could lead to grave human and economic consequences, especially amid global health crises of the coronavirus 2019's (COVID-19) scale. The COVID-19 pandemic exacerbated gender inequalities women face and introduced new challenges that are unprecedented to society at large. Adverse effects of COVID-19, compounded by unintended consequences caused by public health policies such as lockdowns (e.g., delayed or canceled health services), have forced women to face issues ranging from COVID-19 infections and deaths, prolonged unemployment, to unparalleled scale and severity of domestic violence. However, though women face a canopy of debilitating challenges, there is a shortage of research that examines health solutions that can mitigate, if not offset, challenges women experience amid COVID-19. In this paper, we aim to shed light on why timely solutions are needed to mitigate gender inequalities and health disparities women face amid COVID-19 promptly. Furthermore, we underscore the imperative for cost-effective interventions that could shed light on the current health crisis and future pandemics.

Multicenter randomized controlled trial and registry study to assess the safety and efficacy of the NanoKnife® system for the ablation of stage 3 pancreatic adenocarcinoma: overview of study protocols.

BACKGROUND: Irreversible electroporation (IRE) is a local ablation technique utilizing high voltage, low energy direct current to create nanopores in cell membrane which disrupt homeostasis and leads to cell death. Previous reports have suggested IRE may have a role in treating borderline resectable and unresectable Stage 3 pancreatic tumors. METHODS: Patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) will be enrolled in either a randomized, controlled, multicenter trial (RCT) or a multicenter registry study. Subjects enrolled in the RCT must have no evidence of disease progression after 3 months of modified FOLFIRINOX (mFOLFIRINOX) treatment prior to being randomization to either a control or IRE arm. Post-induction and post-IRE treatment for the control and IRE arms, respectively, will be left to the discretion of the treating physician. The RCT will enroll 528 subjects with 264 per arm and include up to 15 sites. All subjects will be followed for at least 24 months or until death. The registry study will include two cohorts of patients with Stage 3 PDAC, patients who received institutional standard of care (SOC) alone and those treated with IRE in addition to SOC. Both cohorts will be required to have undergone at least 3 months of SOC without progression prior to enrollment. The registry study will enroll 532 patients with 266 patients in each arm. All patients will be followed for at least 24 months or until death. The primary efficacy endpoint for both studies will be overall survival (OS). Co-primary safety endpoints will be 1) time from randomization or enrollment in the registry to death or new onset of Grade 4 adverse event (AE), and (2 high-grade complications defined as any AE or serious AE (SAE) with a CTCAE v5.0 grade of 3 or higher. Secondary endpoints will include progression-free survival, cancer-related pain, quality of life, and procedure-related pain for the IRE arm only. DISCUSSION: These studies are intended to provide Level 1 clinical evidence and real-world data demonstrating the clinical utility and safety of the use of IRE in combination with chemotherapy in patients with Stage 3 PDAC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03899636 and NCT03899649. Registered April 2, 2019. Food and Drug Administration (FDA) Investigational Device Exemption (IDE) trial G180278 approved on May 3, 2019.