Keratin 17 modulates the immune topography of pancreatic cancer.

BACKGROUND: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of immunotherapeutic opportunities to extend patient survival. METHODS: Multiplex immunohistochemistry (mIHC) and automated image analysis based on novel computational imaging technology were used to decipher the abundance and spatial distribution of T cells, macrophages, and tumor cells, relative to K17 expression in 235 PDACs. RESULTS: K17 expression had profound effects on the exclusion of intratumoral CD8+ T cells and was also associated with decreased numbers of peritumoral CD8+ T cells, CD16+ macrophages, and CD163+ macrophages (p < 0.0001). The differences in the intratumor and peritumoral CD8+ T cell abundance were not impacted by neoadjuvant therapy, tumor stage, grade, lymph node status, histologic subtype, nor KRAS, p53, SMAD4, or CDKN2A mutations. CONCLUSIONS: Thus, K17 expression correlates with major differences in the immune microenvironment that are independent of any tested clinicopathologic or tumor intrinsic variables, suggesting that targeting K17-mediated immune effects on the immune system could restore the innate immunologic response to PDAC and might provide novel opportunities to restore immunotherapeutic approaches for this most deadly form of cancer.

Modeling Lysosomal Storage Disorders in an Innovative Way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidosis Type II Patients.

Among the many lysosomal storage disorders (LSDs) that would benefit from the establishment of novel cell models, either patient-derived or genetically engineered, is mucopolysaccharidosis type II (MPS II). Here, we present our results on the establishment and characterization of two MPS II patient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population has been isolated from LSD patient samples obtained from the dental pulp. Taking into account our results on the molecular and biochemical characterization of those cells and the fact that they exhibit visible and measurable disease phenotypes, we consider these cells may qualify as a valuable disease model, which may be useful for both pathophysiological assessments and in vitro screenings. Ultimately, we believe that patient-derived dental pulp stem cells (DPSCs), particularly those isolated from human exfoliated deciduous teeth (SHEDs), may represent a feasible alternative to induced pluripotent stem cells (iPSCs) in many labs with standard cell culture conditions and limited (human and economic) resources.

Trauma-focused treatments for victims of interpersonal violence: A comparison of treatment interventions and outcomes.

Background: Interpersonal violence represents a critical public health issue globally, with profound psychological impacts on victims. Objective: The main objective of this study was to analyze the effectiveness of different trauma-focused therapies on mental health outcomes of victims of interpersonal violence, at a community mental health clinic. Methods: Employing a secondary data methodology, the research involves 601 participants who reported being victims of sexual assault (49.1%), domestic violence (44.3%) or sexual trafficking (6.7%). The average age of the participants was 35.54 years, with a majority being female (89.8%). Results: Initial assessments revealed distinct symptomatology among the groups; however, by the ninth therapy session, symptom severity converged across the board, surpassing threshold levels for clinical concern. No significant interaction was observed between the type of trauma-focused therapy and the specific trauma encountered, suggesting a beneficial effect of trauma-focused therapies investigated. This uniformity in therapeutic outcomes underscores the potential of trauma-focused therapies to foster psychological healing in victims of diverse forms of interpersonal violence. Conclusions: The findings advocate for the widespread adoption of trauma-focused therapeutic interventions in community settings, emphasizing their role in the recovery of victims, independent of the nature of the trauma or the specific trauma-focused therapeutic model employed.

Development of Engineered-U1 snRNA Therapies: Current Status.

Splicing of pre-mRNA is a crucial regulatory stage in the pathway of gene expression. The majority of human genes that encode proteins undergo alternative pre-mRNA splicing and mutations that affect splicing are more prevalent than previously thought. Targeting aberrant RNA(s) may thus provide an opportunity to correct faulty splicing and potentially treat numerous genetic disorders. To that purpose, the use of engineered U1 snRNA (either modified U1 snRNAs or exon-specific U1s-ExSpeU1s) has been applied as a potentially therapeutic strategy to correct splicing mutations, particularly those affecting the 5' splice-site (5'ss). Here we review and summarize a vast panoply of studies that used either modified U1 snRNAs or ExSpeU1s to mediate gene therapeutic correction of splicing defects underlying a considerable number of genetic diseases. We also focus on the pre-clinical validation of these therapeutic approaches both in vitro and in vivo, and summarize the main obstacles that need to be overcome to allow for their successful translation to clinic practice in the future.

Dropout from evidence-based trauma treatment in a community mental health clinic serving victims of interpersonal violence.

Trauma-focused psychotherapies are increasingly offered in community-based mental health centers, but little is known about treatment dropout in these settings. The current study explored dropout at different stages of treatment in a treatment-seeking sample of 1,186 adults who experienced interpersonal violence and were offered trauma-focused and non-trauma-focused therapies. A total of 31.6% of participants dropped out before treatment initiation, 28.0% dropped out after treatment initiation and completed a mean of 4.02 (SD = 2.41) sessions, and 40.4% completed a full course of PTSD treatment. Being unemployed, p < .001, and scoring lower on measures of environment factors, p = .045, were significant predictors of pretreatment dropout. Being female, p < .001; Latinx, p = .032; and scoring higher on a measure of social relationships, p = .024, were independent predictors of postinitiation dropout. Individuals who completed nine sessions of treatment displayed significantly lower levels of posttraumatic stress disorder, depression, and anxiety symptoms. The present study provides preliminary evidence that survivors of interpersonal violence who seek therapy tend to drop out early during treatment, and most who complete treatment attain symptom reduction.

Post break-up stalking: Police-officers' perceptions.

Stalking is characterized by persistent unwanted behaviors and can disrupt the lives of victims. Its prevalence has been increasing with time. Due to the recent criminalization of stalking in Portugal and its being an understudied phenomenon, the objective of this study is to assess the perceptions of police officers (n = 1212) about stalking post intimate relationship breakup. We developed an adaptation of the questionnaire "Reasonable Perceptions of Stalking", using vignettes that describe stalking scenarios with the manipulation of severity, and victim and perpetrator sex. The main effects of severity, as well as the victim and the perpetrator's sex, were significant intrasubject variables in the perceptions of stalking and its severity, criminality, victim alert, fear of violence, victim-blaming, and the need for intervention. Participants' sex, previous training, and personal and/or professional experience with stalking were also significant variables concerning participants' perceptions. Our findings show that gender stereotypes are still perpetuated and have important implications for police officer training and intervention.

"It takes a community to save a child": Child trafficking knowledge of the Portuguese community.

This study aims to explore the knowledge of the Portuguese community on child trafficking. Through an online inventory, with a sample of 492 community members, with a mean age of 40.53 and mostly female (70.7%), participants were more knowledgeable about forms of exploitation, risk and vulnerability factors, the profile of the victims, and the situation in Portugal about child trafficking. On the contrary, they were less knowledgeable about the dynamics of child trafficking. Having a college education, and contacting with the subject through informal or/and formal sources were predictors of a higher level of knowledge of child trafficking. This study reinforces the importance of the community as a whole in fighting child trafficking. To protect children against child trafficking, public policies should prioritize the role of the community. An empowered community can actively contribute to the prevention, signaling, and (re)integration of victims of child trafficking.

Clinician-driven artificial intelligence in ophthalmology: resources enabling democratization.

PURPOSE OF REVIEW: This article aims to discuss the current state of resources enabling the democratization of artificial intelligence (AI) in ophthalmology. RECENT FINDINGS: Open datasets, efficient labeling techniques, code-free automated machine learning (AutoML) and cloud-based platforms for deployment are resources that enable clinicians with scarce resources to drive their own AI projects. SUMMARY: Clinicians are the use-case experts who are best suited to drive AI projects tackling patient-relevant outcome measures. Taken together, open datasets, efficient labeling techniques, code-free AutoML and cloud platforms break the barriers for clinician-driven AI. As AI becomes increasingly democratized through such tools, clinicians and patients stand to benefit greatly.

Nanostructured faujasite zeolite as metal ion adsorbent: kinetics, equilibrium adsorption and metal recovery studies.

The hydrothermal synthesis of nano-faujasite has been successfully performed and the effects of some crystallization parameters were investigated, along with the use of this material as a heavy-metal ion adsorbent. X-ray diffraction patterns have shown that the structure of the nano-faujasite is strongly dependent on both the crystallization time and the alkalinity of the synthesis medium. According to N2 physisorption, X-ray fluorescence, SEM/EDS, and solid state 29Si and 27Al NMR data, the produced nano-faujasite consists of a solid with low molar Si/Al ratio (1.7), with high availability of ion exchange sites and high surface area/small particle size, allowing easy diffusion of metal ions to adsorbent active sites. As a consequence, an excellent performance on removal of Cd2+, Zn2+ and Cu2+ ions was found for this solid. The adsorption capacity followed the order Cd2+ (133 mg·g-1) > Zn2+ (115 mg·g-1) > Cu2+ (99 mg·g-1), which agrees with the order of increasing absolute values of the hydration energy of the metal ions. Kinetic studies and adsorption isotherms showed that the metal ion removal takes place by ion exchange on the monolayer surface of the nano-faujasite. The electrochemical recovery of copper in metallic form exhibited an efficiency of 80.2% after 120 min, which suggests that this process can be adequately implemented for full-scale metal removal.