Medical Mistrust and Healthcare Seeking Among Women of Color with Chronic Vulvovaginal Pain.

BACKGROUND: Chronic vulvovaginal pain (CVVP), an umbrella term encompassing several gynecological pain conditions (e.g., vulvodynia, vaginismus), has a prevalence rate of 7-8% in the USA and is characterized by considerable diagnostic delay in patient experience research. Furthermore, current research in this area focuses largely on the experiences of white women, while the experiences of women of color are underrepresented. METHOD: In the present cross-sectional study (N = 488), we surveyed women of color (i.e., Asian, Black, and/or Hispanic/Latinx women) with CVVP about their perceptions and experiences with medical mistrust, healthcare seeking, and healthcare avoidance. RESULTS: Using the suspicion subscale of the Group-Based Medical Mistrust Scale, we found significant racial and ethnic differences in medical suspicion scores, with non-Black Hispanic/Latinx women reporting the highest suspicion scores and non-Hispanic/Latinx Black women reporting the lowest scores. Racial differences disappeared, however, after examining medical mistrust and perceived discrimination as predictors for various healthcare outcomes related to the journey to diagnosis and healthcare avoidance behaviors. We found that while suspicion was a reliable predictor of increased diagnostic delay and healthcare avoidance in many contexts, the results for perceived discrimination were more varied, suggesting considerable nuance in the relationship between medical mistrust, perceived discrimination, and healthcare seeking outcomes. CONCLUSION: These findings point to shared experiences of medical mistrust via suspicion that broadly characterize women of color's experiences in seeking CVVP-related care-future research is needed to examine nuances within racial and ethnic groups regarding their healthcare seeking experiences in the CVVP context.

American Singles' Attitudes Toward Future Romantic/Sexual Partners' COVID-19 Vaccination Status: Evidence for both Vigilance and Indifference in a National Sample.

Around 142 million American adults are currently single; at least half of these singles want to pursue a romantic partner. Romantic dating can involve exposure to numerous people. Thus, dating can significantly impact pathogen exposure risk. In a demographically-representative cross-sectional survey conducted in 2021 (N = 5,000), we examined U.S. American singles' COVID-19 vaccination status, assessed their preferences around a potential partner's COVID-19 vaccination status, and identified demographic subgroups of singles particularly opposed to or indifferent to a partner being vaccinated against COVID-19. Our results showed 65% of participants were fully vaccinated, 10% were partially vaccinated, and 26% were unvaccinated against COVID-19. With regards to partner preferences, half wanted a vaccinated partner; 18.9% wanted a vaccinated partner but would make exceptions; 6.1% wanted an unvaccinated partner; and 25% reported that they did not care about their dating partner's vaccination status. Partner preferences were largely aligned with participants' own vaccination status, such that vaccinated participants preferred vaccinated partners. However, those preferring unvaccinated partners-or those willing to make exceptions for a partner-were most likely to identify as men, younger in age, a political affiliation outside of the two-party political system, a gender or sexual minority, or as a racial minority (i.e., Black/African-American or South Asian). Additionally, participants who were employed (vs. unemployed) were more likely to make exceptions for or prefer an unvaccinated partner. These results suggest that singles prefer homophily in COVID-19 vaccine status, and that minoritized subgroups of singles are more likely to maintain a social network including unvaccinated close others. Supplementary Information: The online version contains supplementary material available at 10.1007/s12119-023-10097-9.

IgA Triggers Cell Death of Neutrophils When Primed by Inflammatory Mediators.

IVIG preparations consisting of pooled IgG are increasingly used for the treatment of autoimmune diseases. IVIG is known to regulate the viability of immune cells, including neutrophils. We report that plasma-derived IgA efficiently triggers death of neutrophils primed by cytokines or TLR agonists. IgA-mediated programmed neutrophil death was PI3K-, p38 MAPK-, and JNK-dependent and evoked anti-inflammatory cytokines in macrophage cocultures. Neutrophils from patients with acute Crohn's disease, rheumatoid arthritis, or sepsis were susceptible to both IgA- and IVIG-mediated death. In contrast to IVIG, IgA did not promote cell death of quiescent neutrophils. Our findings suggest that plasma-derived IgA might provide a therapeutic option for the treatment of neutrophil-associated inflammatory disorders.

Medical avoidance among marginalized groups: the impact of the COVID-19 pandemic.

Medical avoidance is common among U.S. adults, and may be emphasized among members of marginalized communities due to discrimination concerns. In the current study, we investigated whether this disparity in avoidance was maintained or exacerbated during the onset of the COVID-19 pandemic. We assessed the likelihood of avoiding medical care due to general-, discrimination-, and COVID-19-related concerns in an online sample (N = 471). As hypothesized, marginalized groups (i.e., non-White race, Latinx/e ethnicity, non-heterosexual sexual orientation, high BMI) endorsed more general- and discrimination-related medical avoidance than majoritized groups. However, marginalized groups were equally likely to seek COVID-19 treatment as majoritized groups. Implications for reducing medical avoidance among marginalized groups are discussed.

Targeting sialic acid-Siglec interactions to reverse immune suppression in cancer.

Changes in sialic acids in cancer have been observed for many years. In particular, the increase of sialoglycan density or hypersialylation in tumors has been described. Recent studies have identified mechanisms for immune evasion based on sialoglycan interactions with immunoregulatory Siglec receptors that are exploited by tumor cells and microorganisms alike. Siglecs are mostly inhibitory receptors similar to known immune checkpoints including PD-1 or CTLA-4 that are successfully targeted with blocking antibodies for cancer immunotherapy. Here, we summarize the known changes of sialic acids in cancer and the role Siglec receptors play in cancer immunity. We also focus on potential ways to target these Siglec receptors or sialoglycans in order to improve anti-cancer immunity.

Recent Advances in Experimental Allergy.

Atopic disorders are on the rise and pose a great burden on society. A better understanding of the underlying mechanisms is required for the development of improved or novel therapeutic strategies. Here we aim to highlight recent advances in experimental allergy, with a particular focus on proposed treatment alternatives for airway disorders, atopic dermatitis, and food allergy. Furthermore, we discuss recent work focusing on molecular and cellular mechanisms that might offer candidates for future preventive or therapeutic intervention.

Her2-Targeted Therapy Induces Autophagy in Esophageal Adenocarcinoma Cells.

Esophageal adenocarcinoma (EAC) is a highly lethal cancer type with an overall poor survival rate. Twenty to thirty percent of EAC overexpress the human epidermal growth factor receptor 2 (Her2), a transmembrane receptor tyrosine kinase promoting cell growth and proliferation. Patients with Her2 overexpressing breast and gastroesophageal cancer may benefit from Her2 inhibitors. Therapy resistance, however, is well documented. Since autophagy, a lysosome-dependent catabolic process, is implicated in cancer resistance mechanisms, we tested whether autophagy modulation influences Her2 inhibitor sensitivity in EAC. Her2-positive OE19 EAC cells showed an induction in autophagic flux upon treatment with the small molecule Her2 inhibitor Lapatinib. Newly generated Lapatinib-resistant OE19 (OE19 LR) cells showed increased basal autophagic flux compared to parental OE19 (OE19 P) cells. Based on these results, we tested if combining Lapatinib with autophagy inhibitors might be beneficial. OE19 P showed significantly reduced cell viability upon double treatment, while OE19 LR were already sensitive to autophagy inhibition alone. Additionally, Her2 status and autophagy marker expression (LC3B and p62) were investigated in a treatment-naïve EAC patient cohort (n = 112) using immunohistochemistry. Here, no significant correlation between Her2 status and expression of LC3B and p62 was found. Our data show that resistance to Her2-directed therapy is associated with a higher basal autophagy level, which is not per se associated with Her2 status. Therefore, we propose that autophagy may contribute to acquired resistance to Her2-targeted therapy in EAC, and that combining Her2 and autophagy inhibition might be beneficial for EAC patients.

Exploring the Orgasm Gap Across Racial/Ethnic Groups: A Descriptive Analysis.

Orgasm gaps between heterosexual men and women, and for women across sexual orientations, are well-established in research. However, no large-scale assessments of orgasm frequency by race/ethnicity exist. Here, we analyzed 10 years of cross-sectional Singles in America survey data between 2011 and 2021 to investigate the orgasm gap at the intersection of gender and racial/ethnic identity (i.e. White, Black, Hispanic/Latino, and Asian) for heterosexual participants (N = 27,347). White and Hispanic/Latino men reported greater orgasm frequency than Black and Asian men. Hispanic/Latino women reported the greatest orgasm frequency, and Asian women reported the lowest, with White and Black women's frequencies in between. The orgasm gap between men and women was largest for White (d = 0.89) and Asian (d = 0.86) groups, although Asian participants reported a lower orgasm frequency than White participants overall. The orgasm gap was smaller for Hispanic/Latino participants (d = 0.66), because Hispanic/Latino women reported a greater orgasm frequency than other racial/ethnic groups of women. The orgasm gap was smaller for Black participants (d = 0.61), because Black men reported a lower orgasm frequency than some other racial/ethnic groups of men. This descriptive study serves as an important starting point for future research on orgasm experiences across racial/ethnic groups.

Exploring patterns in mental health treatment and interests of single adults in the United States: a secondary data analysis.

Objective: The objective of this study is to examine mental health treatment utilization and interest among the large and growing demographic of single adults in the United States, who face unique societal stressors and pressures that may contribute to their heightened need for mental healthcare. Method: We analyzed data from 3,453 single adults, focusing on those with possible mental health treatment needs by excluding those with positive self-assessments. We assessed prevalence and sociodemographic correlates of mental health treatment, including psychotherapy and psychiatric medication use, and interest in attending psychotherapy among participants who had never attended. Results: 26% were in mental health treatment; 17% were attending psychotherapy, 16% were taking psychiatric medications, and 7% were doing both. Further, 64% had never attended psychotherapy, of which 35% expressed interest in future attendance. There were differences in current psychotherapy attendance and psychiatric medication use by gender and sexual orientation, with women and gay/lesbian individuals more likely to engage in both forms of mental health treatment. Additionally, interest in future psychotherapy among those who had never attended varied significantly by age, gender, and race. Younger individuals, women, and Black/African-American participants showed higher likelihoods of interest in psychotherapy. Conclusion: Our research highlights a critical gap in mental health treatment utilization among single adults who may be experiencing a need for those services. Despite a seemingly higher likelihood of engagement in mental health treatment compared to the general population, only a minority of single adults in our sample were utilizing mental health treatment. This underutilization and the observed demographic disparities in mental health treatment underscore the need for targeted outreach, personalized treatment plans, enhanced provider training, and policy advocacy to ensure equitable access to mental healthcare for single adults across sociodemographic backgrounds.

A sudden change of heart: Warm acclimation can produce a rapid adjustment of maximum heart rate and cardiac thermal sensitivity in rainbow trout.

Warm acclimation in fish is often characterized by an increase in heat tolerance and a reduction in physiological rates to improve the scope to respond to additional challenges including further warming. The speed of these responses can determine their effectiveness. However, acclimation rates vary across levels of biological organization and are poorly understood in part because most research is conducted after an acclimation period of >3 weeks, when acclimation is presumed to be complete. Here we show that when rainbow trout were transferred from 10 to 18 °C, over 50% of the total reduction of maximum heart rate (ƒHmax) (i.e. the thermal compensation at moderate temperatures) occurred within 72 h, with further compensation occurring more gradually over the following 25 days. Also, the ability to increase ƒHmax with acute warming improved within 24 h resulting in a 30% rise in peak ƒHmax, but this ultimately declined again with prolonged (28 days) exposure to 18 °C. In contrast with some previous studies, upper critical temperatures for ƒHmax did not increase. Nonetheless, we demonstrate that rapid cardiac plasticity is possible in rainbow trout and likely blunts the impacts of thermal variation over relatively short timescales, such as that associated with heat waves and migration between water bodies.

PrEP Familiarity, Interest, and Usage Among 364 Black and Hispanic Adults in Indiana.

Pre-exposure prophylaxis, or PrEP, is a once-daily preventative prescription pill against HIV for adults or adolescents who have sex or inject drugs. PrEP may be especially useful among Black and Hispanic Americans, who are particularly at risk for HIV in the United States. In spite of this vulnerability, rates of PrEP use in Black and Hispanic communities are low. Here, we examined familiarity with, prior usage of, and future interest in PrEP among 364 Black and Hispanic Indiana residents. Indiana is an important context for this work, due to severe HIV outbreaks in the area over the last 8 years. Around half of all participants had never heard of PrEP, with Hispanic participants being less familiar than Black participants. Prior PrEP use was low, at around 10%, and was lower for Hispanic than Black participants. Around 21% of all participants reported interest in PrEP after learning of it in our study. Further, participants identified strategies that would make discussions about PrEP with a medical provider more comfortable. Black and Hispanic participants reported feeling the most comfortable with addressing PrEP usage with providers if: (a) the provider was the one who brought up the subject of PrEP, (b) there was written information available to the patient (i.e., brochures), and (c) the patient already knew they qualified for the prescription in terms of personal eligibility and insurance coverage. Additional provider and patient education, as well as openness on the part of the provider, can help to lessen the disparities associated with PrEP need and actual PrEP usage.

An unusually high upper thermal acclimation potential for rainbow trout.

Thermal acclimation, a compensatory physiological response, is central to species survival especially during the current era of global warming. By providing the most comprehensive assessment to date for the cardiorespiratory phenotype of rainbow trout (Oncorhynchus mykiss) at six acclimation temperatures from 15°C to 25°C, we tested the hypothesis that, compared with other strains of rainbow trout, an Australian H-strain of rainbow trout has been selectively inbred to have an unusually high and broad thermal acclimation potential. Using a field setting at the breeding hatchery in Western Australia, thermal performance curves were generated for a warm-adapted H-strain by measuring growth, feed conversion efficiency, specific dynamic action, whole-animal oxygen uptake (MO2) during normoxia and hypoxia, the critical maximum temperature and the electrocardiographic response to acute warming. Appreciable growth and aerobic capacity were possible up to 23°C. However, growth fell off drastically at 25°C in concert with increases in the time required to digest a meal, its total oxygen cost and its peak MO2. The upper thermal tipping points for appetite and food conversion efficiency corresponded with a decrease in the ability to increase heart rate during warming and an increase in the cost to digest a meal. Also, comparison of upper thermal tipping points provides compelling evidence that limitations to increasing heart rate during acute warming occurred well below the critical thermal maximum (CTmax) and that the faltering ability of the heart to deliver oxygen at different acclimation temperatures is not reliably predicted by CTmax for the H-strain of rainbow trout. We, therefore, reasoned the remarkably high thermal acclimation potential revealed here for the Australian H-strain of rainbow trout reflected the existing genetic variation within the founder Californian population, which was then subjected to selective inbreeding in association with severe heat challenges. This is an encouraging discovery for those with conservation concerns for rainbow trout and other fish species. Indeed, those trying to predict the impact of global warming should more fully consider the possibility that the standing intra-specific genetic variation within a fish species could provide a high thermal acclimation potential, similar to that shown here for rainbow trout.

Chronic Vulvovaginal Pain in Patients of Color: Benefits of Partner Supportiveness in Relation to Sexual Dissatisfaction and Distress.

Within the social support literature, individuals who experience chronic pain have shown many positive outcomes and benefits when receiving the appropriate level of emotional support. In the current study, individuals who experience chronic vulvovaginal pain (CVVP) were asked about their partner's supportiveness, other sources of emotional support, and their satisfaction and stress surrounding sexual activity. The participants (n = 333) also identified as people of color, with a majority identifying as African American or Black (n = 227). The participants indicated that their partners were overall supportive of their diagnoses and found other emotional support sources through medical professionals, vulvar/vaginal pain-specific medical information websites, and family or friends. After conducting linear regressions, results showed the partner supportiveness was associated with less distress and less dissatisfaction surrounding sexual activity. Future research is suggested to further examine social support's role for minority patients who experience chronic vulvovaginal pain.

Investigating the Association Between Obsessive-Compulsive Disorder Symptom Subtypes and Health Anxiety as Impacted by the COVID-19 Pandemic: A Cross-Sectional Study.

BACKGROUND: Since the COVID-19 outbreak was declared a global pandemic, public health messages have emphasised the importance of frequent handwashing in limiting the transmission of the virus. Whilst crucial in controlling transmission, such messaging may have an adverse effect on individuals with OCD. METHODS: A cross-sectional study was conducted, with a total of 332 participants recruited. Participants who scored above the optimal cut-off score on the Obsessive-Compulsive Inventory Revised edition (OCI-R) were included in the analysis (n = 254). Scores on the six subscales of the OCI-R were correlated with responses to a COVID-19 Impact measure. RESULTS: Factor analysis of the COVID-19 Impact measure revealed that items loaded on two components of the measure (handwashing and distress-avoidance). Canonical correlation analyses revealed significant associations between the OCI-R subscales and COVID-19 Impact measure, F (12, 490) = 8.14, p = 0.001, and the SHAI subscales with the COVID-19 Impact Measure, F (4, 498) = 8.18, p = 0.001). Specifically, washing and checking OCI-R subscales correlated with both components of the COVID-19 Impact measure, as did the health anxiety and beliefs SHAI subscales. Content analysis revealed disruption to treatment delivery and worsening symptom severity in participants with contamination-related OCD. DISCUSSION: Contamination and checking OCD subtypes have been associated with increased hand-washing behaviour and avoidance of distress-inducing cues. Consideration should be given to targeted support tailored to patients with these subtypes of OCD.

Boron Oxide Nanoparticles Exhibit Minor, Species-Specific Acute Toxicity to North-Temperate and Amazonian Freshwater Fishes.

Boron oxide nanoparticles (nB2O3) are manufactured for structural, propellant, and clinical applications and also form spontaneously through the degradation of bulk boron compounds. Bulk boron is not toxic to vertebrates but the distinctive properties of its nanostructured equivalent may alter its biocompatibility. Few studies have addressed this possibility, thus our goal was to gain an initial understanding of the potential acute toxicity of nB2O3 to freshwater fish and we used a variety of model systems to achieve this. Bioactivity was investigated in rainbow trout (Oncorhynchus mykiss) hepatocytes and at the whole animal level in three other North and South American fish species using indicators of aerobic metabolism, behavior, oxidative stress, neurotoxicity, and ionoregulation. nB2O3 reduced O. mykiss hepatocyte oxygen consumption (MO2) by 35% at high doses but whole animal MO2 was not affected in any species. Spontaneous activity was assessed using MO2 frequency distribution plots from live fish. nB2O3 increased the frequency of high MO2 events in the Amazonian fish Paracheirodon axelrodi, suggesting exposure enhanced spontaneous aerobic activity. MO2 frequency distributions were not affected in the other species examined. Liver lactate accumulation and significant changes in cardiac acetylcholinesterase and gill Na+/K+-ATPase activity were noted in the north-temperate Fundulus diaphanus exposed to nB2O3, but not in the Amazonian Apistogramma agassizii or P. axelrodi. nB2O3 did not induce oxidative stress in any of the species studied. Overall, nB2O3 exhibited modest, species-specific bioactivity but only at doses exceeding predicted environmental relevance. Chronic, low dose exposure studies are required for confirmation, but our data suggest that, like bulk boron, nB2O3 is relatively non-toxic to aquatic vertebrates and thus represents a promising formulation for further development.

Human IgA binds a diverse array of commensal bacteria.

In humans, several grams of IgA are secreted every day in the intestinal lumen. While only one IgA isotype exists in mice, humans secrete IgA1 and IgA2, whose respective relations with the microbiota remain elusive. We compared the binding patterns of both polyclonal IgA subclasses to commensals and glycan arrays and determined the reactivity profile of native human monoclonal IgA antibodies. While most commensals are dually targeted by IgA1 and IgA2 in the small intestine, IgA1+IgA2+ and IgA1-IgA2+ bacteria coexist in the colon lumen, where Bacteroidetes is preferentially targeted by IgA2. We also observed that galactose-α terminated glycans are almost exclusively recognized by IgA2. Although bearing signs of affinity maturation, gut-derived IgA monoclonal antibodies are cross-reactive in the sense that they bind to multiple bacterial targets. Private anticarbohydrate-binding patterns, observed at clonal level as well, could explain these apparently opposing features of IgA, being at the same time cross-reactive and selective in its interactions with the microbiota.

Correction: A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas.

[This corrects the article DOI: 10.1371/journal.pone.0197610.].

A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas.

Paclitaxel is a powerful chemotherapeutic drug, used for the treatment of many cancer types, including esophageal adenocarcinomas (EAC). Autophagy is a lysosome-dependent degradation process maintaining cellular homeostasis. Defective autophagy has been implicated in cancer biology and therapy resistance. We aimed to assess the impact of autophagy on chemotherapy response in EAC, with a special focus on paclitaxel. Responsiveness of EAC cell lines, OE19, FLO-1, OE33 and SK-GT-4, to paclitaxel was assessed using Alamar Blue assays. Autophagic flux upon paclitaxel treatment in vitro was assessed by immunoblotting of LC3B-II and quantitative assessment of WIP1 mRNA. Immunohistochemistry for the autophagy markers LC3B and p62 was applied on tumor tissue from 149 EAC patients treated with neoadjuvant chemotherapy, including pre- and post-therapeutic samples (62 matched pairs). Tumor response was assessed by histology. For comparison, previously published data on 114 primary resected EAC cases were used. EAC cell lines displayed differing responsiveness to paclitaxel treatment; however this was not associated with differential autophagy regulation. High p62 cytoplasmic expression on its own (p ≤ 0.001), or in combination with low LC3B (p = 0.034), was associated with nonresponse to chemotherapy, regardless of whether or not the regiments contained paclitaxel, but there was no independent prognostic value of LC3B or p62 expression patterns for EAC after neoadjuvant treatment. p62 and related pathways, most likely other than autophagy, play a role in chemotherapeutic response in EAC in a clinical setting. Therefore p62 could be a novel therapeutic target to overcome chemoresistance in EAC.

Environmentally relevant concentrations of amine-functionalized copper nanoparticles exhibit different mechanisms of bioactivity in Fundulus Heteroclitus in fresh and brackish water.

The bioavailability of engineered nanomaterials should be limited in marine environments, but uptake and toxicity has been noted in marine fish and invertebrates, albeit at exposure doses far exceeding predicted environmental levels. We examined the bioactivity of amine functionalized copper nanoparticles (nCu; 5-10 nm core diameter) to the euryhaline killifish, Fundulus heteroclitus, in fresh (FW) and brackish water (BW). Free copper dissolution was undetectable in either water type and nCu remained relatively well dispersed in BW, despite the high ionic strength. Exposure to an environmentally relevant concentration of nCu (10 µg L-1) for 48 h significantly increased the maximum rate of oxygen consumption and aerobic scope in BW killifish. This effect was associated with gill remodeling which likely increased surface area and scope for oxygen uptake. In contrast, nCu exposure had no effect on oxygen consumption in FW killifish, but gill Na+/K+-ATPase activity was reduced by >40%, an effect not seen in BW. Osmotic and ionic homeostasis were protected and no indications of physiological or oxidative stress were observed in either FW and BW exposure groups. The results show that functionalized nCu formulations can exhibit bioactivity in both FW and BW and that the underlying mechanisms are different between water types.

Expression analysis of LC3B and p62 indicates intact activated autophagy is associated with an unfavorable prognosis in colon cancer.

Autophagy is a lysosomal degradation and recycling process implicated in cancer progression and therapy resistance. We assessed the impact of basal autophagy in colon cancer (CC) in vitro and ex vivo. Functional autophagy was demonstrated in CC cell lines (LoVo; HT-29) showing a dose-dependent increase of the autophagy markers LC3B, p62 and autophagic vesciles upon increasing concentrations of the autophagy inhibitor chloroquine, which was demonstrated by immunoblotting, immunofluorescence and electron microscopy. Next, tissue microarrays with 292 primary resected CC, with cores from different tumor regions, and normal mucosa were analyzed by immunohistochemistry for LC3B and p62. CC tissue showed LC3B dot-like, p62 dot-like, cytoplasmic and nuclear staining in various levels without significant intratumoral heterogeneity. Tumoral LC3B and p62 expression was significantly higher than in normal tissue (p<0.001). No associations between staining patterns and pathological features (e.g. TNM categories; grading) were observed. Both low LC3B dot-like and low p62 dot-like-cytoplasmic staining were associated with worse overall survival (p=0.005 and p=0.002). The best prognostic discrimination, however, was seen for a combination of LC3B dot-like/p62 dot-like-cytoplasmic staining: high expression of both markers, indicative of impaired activated autophagy, was associated with the best overall survival. In contrast, high LC3B dot-like/low p62 dot-like-cytoplasmic expression, indicative of intact activated autophagy, was associated with the worst outcome (p<0.001 in univariate and HR=0.751; CI=0.607-0.928; p=0.008 in multivariate analysis). These specific expression patterns of LC3B and p62 pointing to different states of autophagy associated with diverging clinical outcomes highlighte the potential significance of basal autophagy in CC biology.