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Background/objectives: Gastric cancer (GC) incidence remains high worldwide, and the survival rate is poor. GC develops from atrophic gastritis (AG), associated with Helicobacter pylori ( Hp ) infection, passing through intestinal metaplasia and dysplasia steps. Since Hp eradication does not exclude GC development, further investigations are needed. New data suggest the possible role of unexplored gastric microbiota beyond Hp in the progression from AG to GC. Aimed to develop a score that could be used in clinical practice to stratify GC progression risk, here was investigate gastric microbiota in AG Hp -negative patients with or without high-grade dysplasia (HGD) or GC., Methods: Consecutive patients undergoing upper endoscopy within an endoscopic follow-up for AG were considered. The antrum and corpus biopsies were used to assess the microbiota composition along the disease progression by sequencing the 16S ribosomal RNA gene. Statistical differences between HGD/GC and AG patients were included in a multivariate analysis., Results: HGD/GC patients had a higher percentage of Bacillus in the antrum and a low abundance of Rhizobiales, Weeksellaceae and Veillonella in the corpus. These data were used to calculate a multiparametric score (Resident Gastric Microbiota Dysbiosis Test, RGM-DT) to predict the risk of progression toward HGD/GC. The performance of RGM-DT in discriminating patients with HGD/GC showed a specificity of 88.9%., Conclusions: The microbiome-based risk prediction model for GC could clarify the role of gastric microbiota as a cancer risk biomarker to be used in clinical practice. The proposed test might be used to personalize follow-up program thanks to a better cancer risk stratification.

A man in his early 40s, with no comorbidities, presented with a swelling in the right postauricular region for 5 days, which had progressively increased in size. He also gave a history of ear pain 2 months back. He denied history of ear discharge, difficulty hearing, giddiness or tinnitus. There was no history of fever, headache or seizures. On examination, the right pinna and external auditory canal were normal. The tympanic membrane was greyish white and intact. A swelling of size 4×3 cm was noted over the right mastoid region. High-resolution CT of the temporal bone showed right otomastoiditis with suspected mastoid cortical breach. Contrast-enhanced MRI was performed and revealed a bony defect in the mastoid cortex with adjacent pachymeningitis, subdural empyema, cerebellar and temporal lobe abscess. The patient was started on empirical intravenous antibiotics. Neurosurgical evaluation was performed and he underwent surgical evacuation of the abscess. 3 weeks later, he underwent a cortical mastoidectomy. He has been on regular follow-up for 6 months with no further complaints., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Currently, risk stratification for pediatric Hodgkin lymphoma is based on clinical factors such as stage, bulk, and systemic symptoms. Novel minimally invasive biomarkers could enhance both prognosis and treatment strategies. Therefore, the plasma extracellular vesicles' microRNA profile was characterized by small RNA sequencing in 36 classical Hodgkin lymphoma cases and these findings were confirmed in an extended cohort of 86 patients by RT-qPCR. It was found that the levels of miR-122-5p at diagnosis were significantly higher (p -value: 0.0002) in patients who relapsed compared to patients in remission. The 5-year event-free survival of cases with high and low levels of miR-122-5p was 65 ± 7% and 93 ± 4%, respectively. MiR-122-5p levels were significantly associated with clinical events in both univariate (p -value: 0.0009) and multivariate (p -value: 0.0037) analysis (hazard ratio 5.8). Target prediction analysis suggests an involvement in the polarization of immune cells. The phenotypic characterization of peripheral blood mononuclear cells in 12 patients showed significantly increased levels of CD4+ T-cells in cases with high miR-122-5p levels as compared to low levels (p -value: 0.048). Moreover, CCL17 (TARC) and IL-6 plasma levels at diagnosis were significantly higher as compared to healthy donors (p -value: ≤0.0001). MiR-122-5p could complement current prognostic assays to identify patients at high risk of relapse.

Peer support models of service provision have become increasingly prevalent in recent decades across multiple health and human services fields. In this scoping review, we examine peer support work within the context of intimate partner violence (IPV) service provision, including an examination of how this approach is conceptualized, the mechanisms underlying it, the impact of professionalism, and the benefits and challenges experienced by IPV peer support workers (PSWs). Three social science databases were searched with keywords related to IPV and peer support work, with additional articles and materials identified via targeted Google searches. The final sample of materials meeting criteria for the study (i.e., focusing on trained peer workers and their experiences serving IPV survivor clients) includes 10 papers and reports published from 1983 to 2022. We find that peer support work is conceptualized as a holistic alternative to traditional forms of IPV service provision, and that PSWs are viewed as occupying a unique role in relation to clients that enhances their ability to provide comprehensive care. However, we also identify several challenges resulting from the increasing professionalization of the IPV field, including a lack of role clarity for PSWs, a need to balance structure and flexibility in peer work service settings, and skepticism toward PSWs from credentialed professionals. Lastly, we find that although PSWs experience advantages from providing services, including enhanced personal growth and healing, they also navigate challenges related to maintaining their own emotional well-being and would benefit from additional training and institutional support., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Atypical cellular neurothekeoma is a rare benign soft-tissue tumour that usually arises in the head and neck region, shoulder girdles, and proximal extremities, predominantly in young women. This dermal neoplasm is under-reported in the literature and is not uncommonly misdiagnosed as a malignant tumour due to its worrisome histologic characteristics. Currently, the diagnosis of cellular neurothekeoma relies on a panel of non-specific immunohistochemical markers and its etiopathogenesis is unknown.Herein, we present the case of an atypical cellular neurothekeoma in the arm of a 49-year-old woman, describing its microscopic features and immunohistochemical profile. Additionally, we present a novel heterozygous predicted inactivating NF1 mutation, not previously reported, which was identified using high-throughput molecular techniques. Such finding might provide insights into the pathogenesis of neurothekeoma, potentially contributing to future refinements in diagnosis, which would enable more precise identification of this neoplasm., Competing Interests: Declarations. Bioethics statement: This study obtained the approval of the ethics committee of the Metropolitan Hospital of the Social Security Fund of Panama. Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Gastric cancer is a heterogeneous collection of tumors characterized by low survival rates. All-trans retinoic acid (retinoic-acid) is a clinically useful therapeutic agent belonging to the chemical family of retinoids, which consists of both natural and synthetic derivatives of vitamin-A. Retinoids are essential components of the normal diet and they regulate different physiological processes. From a therapeutic point of view, retinoic-acid is the first example of clinically useful differentiating agent. Indeed, the differentiating properties of this compound have promoted the use of retinoic-acid as a standard of care in Acute-Promyelocytic-Leukemia, a rare form of acute myeloid leukemia. In this study, we determine the RNA expression of the six isoforms of Retinoic - Acid - Receptors ( RARα / RARβ / RARγ / RXRα / RXRβ / RXRγ ) in view of their potential use as gastric cancer progression markers and/or therapeutic targets. In addition, we evaluate associations between the expression of these receptors and a simplified molecular classification of stomach tumors as well as the clinical characteristics of the cohort of patients analyzed. Finally, we define the prognostic value of the various Retinoic - Acid - Receptors in gastric cancer., Methods: In this single institution and retrospective RAR-GASTRIC study, we consider 55 consecutive gastric cancer patients. We extract total RNA from the pathological specimens and we perform a NanoString Assay using a customized panel of genes. This allows us to determine the expression levels of the RAR and RXR mRNAs as well as other transcripts of interest., Results: Our data demonstrate ubiquitous expression of the RAR and RXR mRNAs in gastric cancers. High levels of RARα , RARβ , RXRα and RXRβ show a significant association with stage IV tumors, " de novo " metastatic disease, microsatellite-stable-status, epithelial-to-mesenchymal-transition, as well as PIK3CA and TP53 expression. Finally, we observe a worse overall - survival in gastric cancer patients characterized by high RARα / RARβ / RARγ / RXRβ mRNA levels., Conclusions: In gastric cancer, high expression levels of RARα / RARβ / RARγ / RXRβ transcripts are associated with poor clinical and molecular characteristics as well as with reduced overall - survival . Our data are consistent with the idea that RARα , RARβ , RARγ and RXRβ represent potential prognostic markers and therapeutic targets of gastric cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Garattini, Basile, De Re, Brisotto, Miolo, Canzonieri, Aprile, Corvaja, Buriolla, Garattini and Puglisi.)

Background: Adhesive small bowel obstruction (ASBO) is a leading cause of hospitalization in emergency surgery. The occurrence of bowel ischemia significantly increases the morbidity and mortality rates associated with this condition. Current clinical, biochemical and radiological parameters have poor predictive value for bowel ischemia. This study is designed to ascertain predictive elements for the progression to bowel ischemia in patients diagnosed with non-strangulated ASBO who are initially managed through conservative therapeutic approaches., Methods: The study was based on the previously collected medical records of 128 patients admitted to the Department of Acute Care Surgery of Padua General Hospital, from August 2020 to April 2023, with a diagnosis of non-strangulated adhesive small bowel obstruction, who were then operated for failure of conservative treatment. The presence or absence of bowel ischemia was used to distinguish the two populations. Clinical, biochemical and radiological data were used to verify whether there is a correlation with the detection of bowel ischemia., Results: We found that a Neutrophil-Lymphocyte ratio (NLR) > 6.8 (OR 2.9; 95% CI 1.41-6.21), the presence of mesenteric haziness (OR 2.56; 95% CI 1.11-5.88), decreased wall enhancement (OR 4.3; 95% CI 3.34-10.9) and free abdominal fluid (OR 2.64; 95% CI 1.08-6.16) were significantly associated with bowel ischemia at univariate analysis. At the multivariate logistic regression analysis, only NLR > 6.8 (OR 5.9; 95% CI 2.2-18.6) remained independent predictive factor for small bowel ischemia in non-strangulated adhesive small bowel obstruction, with 78% sensitivity and 65% specificity., Conclusions: NLR is a straightforward and reproducible parameter to predict bowel ischemia in cases of non-strangulated adhesive small bowel obstruction. Employing NLR during reevaluation of patients with this condition, who were initially treated conservatively, can help the acute care surgeons in the early prediction of bowel ischemia onset., (© 2024. The Author(s).)

We report the first case of relapsing anti-GBM disease secondary to alemtuzumab in a 24-year-old female with relapsing-remitting multiple sclerosis. Initial anti-GBM disease was detected 10 months after alemtuzumab was given and was diagnosed by demonstrating high anti-GBM antibody titers and with a confirmatory kidney biopsy. The patient presented with a rapidly progressive glomerulonephritis with no pulmonary involvement. After appropriate treatment, the patient went into remission with undetectable anti-GBM antibodies. However, 20 months later, the patient re-presented with relapsing anti-GBM disease. Despite aggressive treatment, the patient became dialysis-dependent., (© 2023. Crown.)

Background: Activation of CD28 on multiple myeloma (MM) plasma cells, by binding to CD80 and CD86 on dendritic cells, decreases proteasome subunit expression in the tumor cells and thereby helps them evade being killed by CD8 + T cells. Understanding how CD28 activation leads to proteasome subunit downregulation is needed to design new MM therapies., Methods: This study investigates the molecular pathway downstream of CD28 activation, using an in vitro model consisting of myeloma cell lines stimulated with anti-CD28-coated beads., Results: We show that CD28 engagement on U266 and RPMI 8226 cells activates the PI3K/AKT pathway, reduces miR29b expression, increases the expression of DNA methyltransferase 3B (DNMT3B, a target of miR29b), and decreases immunoproteasome subunit expression. In vitro transfection of U266 and RPMI 8226 cells with a miR29b mimic downregulates the PI3K/AKT pathway and DNMT3B expression, restores proteasome subunit levels, and promotes myeloma cell killing by bone marrow CD8 + T cells from MM patients. Freshly purified bone marrow plasma cells (CD138 + ) from MM patients have lower miR29b and higher DNMT3B (mRNA and protein) than do cells from patients with monoclonal gammopathy of undetermined significance. Finally, in MM patients, high DNMT3B levels associate with shorter overall survival., Conclusions: Altogether, this study describes a novel molecular pathway in MM. This pathway starts from CD28 expressed on tumor plasma cells and, through the PI3K-miR29b-DNMT3B axis, leads to epigenetic silencing of immunoproteasome subunits, allowing MM plasma cells to elude immunosurveillance. This discovery has implications for the design of innovative miR29b-based therapies for MM., (© 2024. The Author(s).)

Coping with dementia requires an integrated approach encompassing personal, health, research, and community domains. Here we describe "Walking the Talk for Dementia," an immersive initiative aimed at empowering people with dementia, enhancing dementia understanding, and inspiring collaborations. This initiative involved 300 participants from 25 nationalities, including people with dementia, care partners, clinicians, policymakers, researchers, and advocates for a 4-day, 40 km walk through the Camino de Santiago de Compostela, Spain. A 2-day symposium after the journey provided novel transdisciplinary and horizontal structures, deconstructing traditional hierarchies. The innovation of this initiative lies in its ability to merge a physical experience with knowledge exchange for diversifying individuals' understanding of dementia. It showcases the transformative potential of an immersive, embodied, and multi-experiential approach to address the complexities of dementia collaboratively. The initiative offers a scalable model to enhance understanding, decrease stigma, and promote more comprehensive and empathetic dementia care and research., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Research has examined the relationship between femicides, understood as the killing of any woman, and intimate partner violence (IPV). Additionally, women have been found to seek out formal help when they deem their experiences to be severe, yet many reasons prevent them from doing so; hindering our ability to interrupt the cycle of violence and further victimization. Using the Salvadoran 2017 Violence Against Women National Survey, this study examines the relationships between femicide attempts, IPV, and formal help-seeking. We find a significant positive relationship between experiencing a femicide attempt and IPV, and specific reasons for not seeking formal help., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The primary objective of this study was to investigate the potential role of tissue osteopontin, also known as secreted phosphoprotein 1 ( SPP1 ), as a contributing factor to an unfavorable prognosis in classical Hodgkin's lymphoma (HL) patients who received the same treatment protocol. The study involved 44 patients aged 4-22 years, with a median follow-up period of 3 years. Patients with higher levels of SPP1 were associated with tissue necrosis and inflammation, and there was a trend toward a poorer prognosis in this group. Before therapy, we found a correlation between positron emission tomography (PET) scans and logarithmic SPP1 levels ( p = 0.035). However, the addition of SPP1 levels did not significantly enhance the predictive capacity of PET scans for recurrence or progression. Elevated SPP levels were associated with tissue mRNA counts of chemotactic and inflammatory chemokines, as well as specific monocyte/dendritic cell subtypes, defined by IL-17RB, PLAUR, CXCL8, CD1A, CCL13, TREM1 , and CCL24 markers. These findings contribute to a better understanding of the potential factors influencing the prognosis of HL patients and the potential role of SPP1 in the disease. While the predictive accuracy of PET scans did not substantially improve during the study, the results underscore the complexity of HL and highlight the relationships between SPP1 and other factors in the context of HL relapse.

Background: Surgical oncological emergencies represent a frequent challenge in acute settings, with postoperative courses characterized by high morbidity and mortality. An accurate selection of patients who could benefit from surgery is essential to avoid unnecessary invasive treatment. In this study, we tried to determine if advanced age (>80 years) represents a risk factor for negative short-term outcome in patients undergoing emergency surgery for acute abdominal oncological illness., Methods: We retrospectively analyzed the records of patients who underwent emergency oncological surgery at the Department of Acute Care Surgery of Padua General Hospital from January 2018 to December 2022. One hundred two cancer patients were included in the study. Among them, 42 were aged ≥80 years (41%). Multiple preoperative and postoperative parameters were recorded, and the follow-up period was at least 90 days. Multivariate logistic regression analyses were used to identify factors associated with short-term postoperative outcomes., Results: In the octogenarian group, 30-day mortality was 11% vs. 9.5% in the younger group [p = not significant ( ns )] and 90-day mortality was 17.6% in the octogenarian group vs. 20.5% in the younger group (p = ns ). Postoperative morbidity and hospital length of stay were not significantly different in the two groups. Low albumin levels [odds ratio (OR) 30.6, 9.51-87.07] and elevated lactate dehydrogenase (LDH) levels (OR 26.4, 9.18-75.83) were predictive for short-term mortality in surgical oncological emergencies., Conclusion: Advanced age is not a risk factor for negative outcomes in surgical oncological emergencies. Therefore, surgical options should be considered in octogenarians with oncological emergencies and acceptable clinical conditions. Serum albumin levels and LDH can help predict the postoperative outcome after surgery for oncological emergencies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor LS declared a past co-authorship with the authors AF, CS, and SS., (Copyright © 2023 Friziero, Sperti, Riccio, Zuin, Vallese, Serafini, Amico, Valli, Da Re, Baldan, Valmasoni and Da Dalt.)

Gastric cancer (GC) is a highly malignant disease affecting humans worldwide and has a poor prognosis. Most GC cases are detected at advanced stages due to the cancer lacking early detectable symptoms. Therefore, there is great interest in improving early diagnosis by implementing targeted prevention strategies. Markers are necessary for early detection and to guide clinicians to the best personalized treatment. The current semi-invasive endoscopic methods to detect GC are invasive, costly, and time-consuming. Recent advances in proteomics technologies have enabled the screening of many samples and the detection of novel biomarkers and disease-related signature signaling networks. These biomarkers include circulating proteins from different fluids (e.g., plasma, serum, urine, and saliva) and extracellular vesicles. We review relevant published studies on circulating protein biomarkers in GC and detail their application as potential biomarkers for GC diagnosis. Identifying highly sensitive and highly specific diagnostic markers for GC may improve patient survival rates and contribute to advancing precision/personalized medicine.

This study examined the impact of child abuse on intimate partner violence (IPV) among a representative sample of 3,296 women using the Violence Against Women National Survey data from El Salvador. We found that child physical, sexual, and psychological abuse were independently associated with IPV, and experiencing child polyvictimization, along with having a controlling husband increased the risk of IPV victimization. To prevent child abuse (poly)victimization and IPV, and its negative consequences in El Salvador, implementing programs that focus on group training for women and men, as well as, community mobilizations that involve multiple stakeholders with multiple approaches would be beneficial., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The presence of various organic and inorganic contaminants in wastewater leads to serious health effects on humans and ecosystems. Industrial effluents have been considered as noticeable sources of contaminating water streams. These effluents directly liberate the pollutants such as dye molecules and heavy metal ions into the environment. In the present study, three biowaste materials (groundnut shell powder, coconut coir powder and activated corn leaf carbon) were utilized and compared for the removal of acid blue dye 113 from aqueous solutions. The characterization study of newly prepared sorbent material (H 3 PO 4 -activated corn leaf carbon) and the other utilized sorbents was carried out by Scanning Electron Microscope (SEM) and Fourier Transform Infrared Spectrophotometer (FTIR), along with Energy Dispersive X-Ray (EDX) Analysis. The influence of experimental conditions such as pH, initial dye concentration, temperature, contact time, and sorbent dosage on the removal efficiency of the dye were appraised. The adsorption isotherm and kinetic result of acid blue dye 113 adsorption onto the sorbents best obeyed from Sips and pseudo-second-order kinetic model. Overall, the outcomes confirmed that the newly synthesized sorbent material (carbonized H 3 PO 4 -activated corn leaf) has superior adsorption capacity, rapid adsorption, and higher suitability for the removal of toxic dyes from the contaminated waters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Intimate partner violence (IPV) victims tend to suffer from various mental health issues. Mental health issues, including suicidal thoughts and attempts caused by IPV victimization, might be more severe among women in El Salvador, where violence against women is prevalent overall. Although polyvictimization, which is defined as experiencing more than one type of violence by one or multiple partners, is associated with more severe mental health consequences than victimization by just a single form of violence due to accumulative trauma, not enough attention has been paid to this phenomenon among Salvadoran women. Thus, guided by trauma theory, this study aimed to examine the impact of polyvictimization from different types of violence (i.e., physical, sexual, emotional, and economic) on suicidal thoughts and attempts among Salvadoran women using the 2017 Violence Against Women National Survey. A nationally representative sample of 3,074 Salvadoran women aged 15 years or older and who had experienced an intimate relationship in their lifetime, recruited through a multistage random sampling design, was analyzed in this study using logistic regression analyses. We found that psychological and economic violence, along with physical and sexual violence, had statistically significant associations with suicidal thoughts and attempts, and polyvictimization increased suicidal thoughts and attempts. Based on this study's findings, we recommend effective research and practice or intervention implementation for addressing IPV and associated mental health problems among Salvadoran women.

Aim: To evaluate correlation of PRF and HAS with glycemic control (HbA1c) and other systemic parameters amongst the chronic periodontitis patients., Materials and Methods: Twenty-seven non-smoker, non-tobacco users, non-alcoholic moderate chronic periodontitis volunteers (Stage II, Grade A or B), aging between 40 and 50 years of both genders with type 2 diabetes mellitus (T2DM, HbA1c >6.5%) or without T2DM (HbA1c <6.5%), were recruited. After recording vitals and demographic parameters, 20 ml of intravenous fasting blood was collected, of which 11 ml blood was used for investigating complete blood count, lipid profile, glycated hemoglobin (HbA1c), C-reactive protein, and fasting insulin level. As per the standard protocol, PRF and HAS was prepared from the 9-ml blood sample of the patients. PRF obtained was quantified using Wensar's analytical balance with a readability of 0.0001 g. Prepared HAS from the fibrin clot was quantified using a micropipette and stored in 2 ml Eppendorf vials., Results: Mean values of PRF and HAS obtained in the study were 2.0089 ± 0.844 g (ranged between 0.0 g and 3.968 g) and 1.540 ± 0.552 ml (ranged between 0.00 and 3.500 ml), respectively. The amount of PRF and HAS obtained were significantly higher in non-diabetic patients (mean 2.3093 g and 1.743 ml, respectively) as compared to diabetic patients (mean 1.5762 g and 1.266 ml, respectively). Results suggested a significant correlation between HbA1c level and quantification of PRF ( P =0.007) and HAS ( P =0.037), whereas no correlation was observed between HbA1c levels and hematologic, lipid, and demographic parameters., Conclusion: Within the limitation of the present study, it can be concluded that a significant correlation exists between the HbA1c level and quantification of PRF and HAS., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Introduction: Mapping of the human genome, together with the broad understanding of new biomolecular pathways involved in cancer development, represents a huge dividing line for advances in cancer treatment. This special article aims to express the next evolution of cancer therapy, while also considering the challenges and uncertainties facing future directions., Area Covered: The recent achievements of medical science in the oncology field concern both new diagnostic techniques, such as liquid biopsy, and therapeutic strategies with innovative anticancer drugs. Although several molecular characteristics of tumors are linked to the tissue of origin, some mutations are shared by multiple tumor histologies, thus paving the way for what is called 'precision oncology.' The article highlights the importance of identifying new mutations and biomolecular pathways that can be pursued with new anticancer drugs., Expert Opinion: Oncology and medical science have made great progress in understanding new molecular targets; being able to early identify tumor markers that are not confined to a single organ through minimally invasive diagnostic techniques allows us to design new effective therapeutic strategies. Multidisciplinary teams now aim to evaluate the most appropriate and personalized diagnostic/therapeutic approach for the individual patient.

A number of studies are underway to gain a better understanding of the role of immunity in the pathogenesis of hepatocellular carcinoma and to identify subgroups of individuals who may benefit the most from systemic therapy according to the etiology of their tumor. Human leukocyte antigens play a key role in antigen presentation to T cells. This is fundamental to the host's defense against pathogens and tumor cells. In addition, HLA-specific interactions with innate lymphoid cell receptors, such those present on natural killer cells and innate lymphoid cell type 2, have been shown to be important activators of immune function in the context of several liver diseases. More recent studies have highlighted the key role of members of the non-classical HLA-Ib and the transcript adjacent to the HLA-F locus, FAT10, in hepatocarcinoma. The present review analyzes the major contribution of these molecules to hepatic viral infection and hepatocellular prognosis. Particular attention has been paid to the association of natural killer and Vδ2 T-cell activation, mediated by specific HLA class Ib molecules, with risk assessment and novel treatment strategies to improve immunotherapy in HCC.

Germination of Ceratopteris richardii spores is initiated by light and terminates 3-4 days later with the emergence of a rhizoid. Early studies documented that the photoreceptor for initiating this response is phytochrome. However, completion of germination requires additional light input. If no further light stimulus is given after phytochrome photoactivation, the spores do not germinate. Here we show that a crucial second light reaction is required, and its function is to activate and sustain photosynthesis. Even in the presence of light, blocking photosynthesis with DCMU after phytochrome photoactivation blocks germination. In addition, RT-PCR showed that transcripts for different phytochromes are expressed in spores in darkness, and the photoactivation of these phytochromes results in the increased transcription of messages encoding chlorophyll a/b binding proteins. The lack of chlorophyll-binding protein transcripts in unirradiated spores and their slow accumulation makes it unlikely that photosynthesis is required for the initial light reaction. This conclusion is supported by the observation that the transient presence of DCMU, only during the initial light reaction, had no effect on germination. Additionally, the [ATP] in Ceratopteris richardii spores increased coincidentally with the length of light treatment during germination. Overall, these results support the conclusion that two distinct light reactions are required for the germination of Ceratopteris richardii spores., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cannon, Sabharwal, Salmi, Chittari, Annamalai, Leggett, Morris, Slife, Clark and Roux.)

Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture., Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO., Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level., Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO., Funding: German Research Foundation (DFG)., Competing Interests: Declaration of interests MDR reports consulting fees from Roche Diagnostics and Medtronic; leadership or fiduciary role in the European Society of Gastrointestinal Endoscopy (ESGE) and World Endoscopy Organization (WEO). All other authors report no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

In this study, we aimed to assess the accuracy of the proposed novel, noninvasive serum DSC test in predicting the risk of gastric cancer before the use of upper endoscopy. To validate the DSC test, we enrolled two series of individuals living in Veneto and Friuli-Venezia Giulia, Italy (n = 53 and n = 113, respectively), who were referred for an endoscopy. The classification used for the DSC test to predict gastric cancer risk combines the coefficient of the patient's age and sex and serum pepsinogen I and II, gastrin 17, and anti- Helicobacter pylori immunoglobulin G concentrations in two equations: Y1 and Y2. The coefficient of variables and the Y1 and Y2 cutoff points (>0.385 and >0.294, respectively) were extrapolated using regression analysis and an ROC curve analysis of two retrospective datasets (300 cases for the Y1 equation and 200 cases for the Y2 equation). The first dataset included individuals with autoimmune atrophic gastritis and first-degree relatives with gastric cancer; the second dataset included blood donors. Demographic data were collected; serum pepsinogen, gastrin G17, and anti- Helicobacter pylori IgG concentrations were assayed using an automatic Maglumi system. Gastroscopies were performed by gastroenterologists using an Olympus video endoscope with detailed photographic documentation during examinations. Biopsies were taken at five standardized mucosa sites and were assessed by a pathologist for diagnosis. The accuracy of the DSC test in predicting neoplastic gastric lesions was estimated to be 74.657% (65%CI; 67.333% to 81.079%). The DSC test was found to be a useful, noninvasive, and simple approach to predicting gastric cancer risk in a population with a medium risk of developing gastric cancer.

Aim: To present our experience on osteosarcomas of the hands and review the existing literature pertaining osteosarcomas in this extremely rare location., Methods: and results: Seven cases of osteosarcomas of the hands were reviewed, and a literature search of all primary osteosarcomas of the hands was performed. All tumors occurred in adults (mean age, 41 years) and were located mainly around the metacarpophalangeal joints. All patients presented with localized long-lasting pain as main symptom. The mean size at diagnosis was 33 mm. Three tumors were low-grade central osteosarcomas, 1 low-grade central chondroblastoma-like osteosarcoma and 3 high-grade osteosarcomas. All tumors were positive for mouse double-minute 2 homolog (MDM2) immunohistochemistry. Three cases yielded results with fluorescence in-situ amplification for MDM2 (12q15)/CEP12. At last follow-up, one patient with a high-grade osteosarcoma was dead of disease. The literature review revealed similar demographic and site distribution of osteosarcomas within the hands than our series and an unusually high proportion of low-grade central and parosteal osteosarcomas when compared to the proportion of these infrequent neoplasms in the whole skeleton., Conclusions: osteosarcomas of hands present in older individuals compared to the population affected by conventional osteosarcomas of all sites. Importantly from a diagnostic, therapeutic and prognostic points of view, around 40% of osteosarcomas of the hands are low-grade osteosarcomas of the central or parosteal types., Competing Interests: Conflict of interest Authors declare no present or potential conflicts of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Intimate partner violence (IPV) literature addresses the ways in which women oppose violent male partners through acts of "everyday resistance." There is a limited understanding, however, of the relationship between women's resistance and their formal help-seeking in the context of IPV. Our scoping review, which includes 74 articles published in English-language journals between 1994 and 2017, attempts to help fill this gap by developing systematic knowledge regarding the following research questions: (1) How are formal institutional responses discussed within the literature on resistance to IPV? (2) How does institutional help-seeking facilitate or obstruct IPV survivors' personal efforts to resist violence? We find that institutions and organizations succeed in facilitating resistance processes when they counter victim-blaming ideas and provide IPV survivors with shared community and a sense of control over their futures. However, they fall short in terms of helping survivors by expecting survivors to adhere to a rigid narrative about appropriate responses to violence, devoting insufficient attention to individual-level factors impacting survivors' vulnerability and ability to access help, and replicating abuse dynamics when interacting with survivors. Policy and practice implications are discussed.

Scholars acknowledge that women oppose male intimate partner violence (IPV). Yet there is limited comprehensive knowledge regarding how women's bodies and embodiment, that is, their physical and emotional practices and the cultural and social systems that influence them, figure in this process. Our scoping review helps fill this gap by analyzing and synthesizing 74 research articles published in English-language scholarly journals between 1994 and 2017 to address three research questions: (1) How does existing IPV research conceptualize resistance? (2) To what extent do the body and embodiment appear in this research? and (3) What common themes emerge from investigation of the role of embodiment and the body in the context of IPV? The articles identify several subtypes of resistance strategies including avoidance, help-seeking, violent action, and leaving a violent relationship. The reviewed research also regularly describes women's physical and emotional states in the context of IPV. Only a small number of these texts, however, define or conceptualize embodiment. Our analysis of the manner in which the body figures in women's resistance to IPV yielded four themes: (1) the active body , (2) the injured/constrained body , (3) the interactive body , and (4) the transformative body . We conclude with a discussion of policy and practice implications, such as the need to increase awareness about how institutions enforce embodied norms among victims and use the body to assign blame and/or proffer assistance in the context of IPV.

Scholars widely acknowledge that women oppose male violence and control in intimate relationships. Yet there is limited comprehensive knowledge of how resistance features in intimate partner violence (IPV) research across the social sciences. Our scoping review helps fill this gap, analyzing and synthesizing 74 research articles published in English-language scholarly journals between 1994 and 2017. Our review is guided by the following questions: (1) How is research on IPV and resistance designed and executed? (2) How do IPV researchers define the term resistance? (3) What specific types of resistance do IPV researchers discuss in their work? (4) What policy and practice implications are provided by current literature on women's resistance to IPV? We find that scholarship on resistance to IPV is varied, spanning 10 scholarly disciplines with research samples drawn from 19 countries. Studies overwhelmingly used qualitative data, gathered through a range of techniques. The 42 articles that explicitly or implicitly defined resistance either conceptualized the term in the context of power relations, defined it as a form of agency, or understood resistance as a mechanism of physical, economic, and existential survival. Articles also identify several subtypes of resistance strategies including avoidance, help-seeking, active opposition, violent action, and leaving a violent relationship. In terms of practice and policy, articles identify several ways in which institutions fail to meet women's needs, and recommend training so providers and legal personnel may better assist IPV victims.

Currently-available therapies for newly-diagnosed pediatric and adolescent patients with Hodgkin lymphoma result in >95% survival at 5 years. Long-term survivors may suffer from long-term treatment-related side effects, however, so the past 20 years have seen clinical trials for children and adolescents with HL gradually abandon the regimens used in adults in an effort to improve this situation. Narrower-field radiotherapy can reduce long-term toxicity while maintaining good tumor control. Various risk-adapted chemo-radiotherapy strategies have been used. Early assessment of tumor response with interim positron emission tomography and/or measuring metabolic tumor volume has been used both to limit RT in patients with favorable characteristics and to adopt more aggressive therapies in patients with a poor response. Most classical Hodgkin's lymphoma relapses occur within 3 years of initial treatment, while relapses occurring 5 years or more after diagnosis are rare. As the outcome for patients with relapsed/refractory classical Hodgkin lymphoma remains unsatisfactory, new drugs have been proposed for its prevention or treatment. This review summarizes the important advances made in recent years in the management of pediatric and adolescent with classical Hodgkin lymphoma, and the novel targeted treatments for relapsed and refractory classical Hodgkin lymphoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 De Re, Repetto, Mussolin, Brisotto, Elia, Lopci, d’Amore, Burnelli and Mascarin.)

Rationale: Therapy response evaluation by 18F-fluorodeoxyglucose PET/CT (FDG PET) has become a powerful tool for the discrimination of responders from non-responders in pediatric Hodgkin lymphoma (HL). Recently, volumetric analyses have been regarded as a valuable tool for disease prognostication and biological characterization in cancer. Given the multitude of methods available for volumetric analysis in HL, the AIEOP Hodgkin Lymphoma Study Group has designed a prospective analysis of the Italian cohort enrolled in the EuroNet-PHL-C2 trial. Methods: Primarily, the study aimed to compare the different segmentation techniques used for volumetric assessment in HL patients at baseline (PET1) and during therapy: early (PET2) and late assessment (PET3). Overall, 50 patients and 150 scans were investigated for the current analysis. A dedicated software was used to semi-automatically delineate contours of the lesions by using different threshold methods. More specifically, four methods were applied: (1) fixed 41% threshold of the maximum standardized uptake value (SUVmax) within the respective lymphoma site (V41%), (2) fixed absolute SUV threshold of 2.5 (V2.5); (3) SUVmax(lesion)/SUVmean liver >1.5 (Vliver); (4) adaptive method (AM). All parameters obtained from the different methods were analyzed with respect to response. Results: Among the different methods investigated, the strongest correlation was observed between AM and Vliver (rho > 0.9; p < 0.001 for SUVmean, MTV and TLG at all scan timing), along with V2.5 and AM or Vliver (rho 0.98, p < 0.001 for TLG at baseline; rho > 0.9; p < 0.001 for SUVmean, MTV and TLG at PET2 and PET3, respectively). To determine the best segmentation method, we applied logistic regression and correlated different results with Deauville scores at late evaluation. Logistic regression demonstrated that MTV (metabolic tumor volume) and TLG (total lesion glycolysis) computation according to V2.5 and Vliver significantly correlated to response to treatment (p = 0.01 and 0.04 for MTV and 0.03 and 0.04 for TLG, respectively). SUVmean also resulted in significant correlation as absolute value or variation. Conclusions: The best correlation for volumetric analysis was documented for AM and Vliver, followed by V2.5. The volumetric analyses obtained from V2.5 and Vliver significantly correlated to response to therapy, proving to be preferred thresholds in our pediatric HL cohort.

Purpose of Review: Review work to create and evaluate educational materials that could serve as a primary prevention strategy to help both providers and patients in Panama, Colombia, and the USA reduce disease burden of Toxoplasma infections., Recent Findings: Educational programs had not been evaluated for efficacy in Panama, USA, or Colombia., Summary: Educational programs for high school students, pregnant women, medical students and professionals, scientists, and lay personnel were created. In most settings, short-term effects were evaluated. In Panama, Colombia, and USA, all materials showed short-term utility in transmitting information to learners. These educational materials can serve as a component of larger public health programs to lower disease burden from congenital toxoplasmosis. Future priorities include conducting robust longitudinal studies of whether education correlates with reduced adverse disease outcomes, modifying educational materials as new information regarding region-specific risk factors is discovered, and ensuring materials are widely accessible., Competing Interests: Conflict of Interest Denis Limone Pharm D,is Chairman , shareholder and CEO and Raphael Piarroux Pharm D, PhD, is RandD Director and employee at LDBio Diagnostics. A patent application was submitted in the United States for the development of the whole blood point of care test with the scientists at the University of Chicago to insure its continued high quality performance and reproducibility. The authors declare no other competing interests..

Emerging evidence indicates that various cancers can gain resistance to targeted therapies by acquiring lineage plasticity. Although various genomic and transcriptomic aberrations correlate with lineage plasticity, the molecular mechanisms enabling the acquisition of lineage plasticity have not been fully elucidated. We reveal that Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling is a crucial executor in promoting lineage plasticity-driven androgen receptor (AR)-targeted therapy resistance in prostate cancer. Importantly, ectopic JAK-STAT activation is specifically required for the resistance of stem-like subclones expressing multilineage transcriptional programs but not subclones exclusively expressing the neuroendocrine-like lineage program. Both genetic and pharmaceutical inhibition of JAK-STAT signaling resensitizes resistant tumors to AR-targeted therapy. Together, these results suggest that JAK-STAT are compelling therapeutic targets for overcoming lineage plasticity-driven AR-targeted therapy resistance., (© 2022. The Author(s).)

Classical pediatric Hodgkin Lymphoma (HL) is a rare malignancy. Therapeutic regimens for its management may be optimized by establishing treatment response early on. The aim of this study was to identify plasma protein biomarkers enabling the prediction of relapse in pediatric/adolescent HL patients treated under the pediatric EuroNet-PHL-C2 trial. We used untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics at the time of diagnosis—before any therapy—as semiquantitative method to profile plasma proteins specifically associated with relapse in 42 children with nodular sclerosing HL. In both the exploratory and the validation cohorts, six proteins (apolipoprotein E, C4b-binding protein α chain, clusterin, fibrinogen γ chain, prothrombin, and vitronectin) were more abundant in the plasma of patients whose HL relapsed (|fold change| ≥ 1.2, p < 0.05, Student’s t-test). Predicting protein function with the Gene Ontology classification model, the proteins were included in four biological processes (p < 0.01). Using immunoblotting and Luminex assays, we validated two of these candidate biomarkers—C4b-binding protein α chain and clusterin—linked to innate immune response function (GO:0045087). This study identified C4b-binding protein α chain and clusterin as candidate early plasma biomarkers of HL relapse, and important for the purpose of shedding light on the molecular scenario associated with immune response in patients treated under the EuroNet-PHL-C2 trial.

Background: Long Covid Syndrome (LCS) is used to describe signs and symptoms that continue or develop after acute COVID-19 infection. Natural history and treatment of this syndrome are still poorly understood, even if evidences suggest the potential role of physical rehabilitation in improving symptoms in these patients., Aim of the Study: The aim of the present study was to evaluate effectiveness, safety and feasibility of an out-of-hospital multidisciplinary rehabilitation (MDR) program, based both on physical and psychological reconditioning, in reducing symptoms and improving physical fitness and psychological parameters in patients with LCS., Methods: Thirty consecutive patients with LCS (18 males, mean age 58 years) underwent an accurate medical screening process including anthropometric and muscular strength evaluation, cardiopulmonary exercise test, quality of life (QoL) and psychological appraisal before and after a MDR program., Results: At baseline, all LCS patients were strongly symptomatic and showed severe impairments in physical performance, QoL and psychological parameters. No adverse effects and dropouts were observed during the exercise training sessions. After the MDR program, COVID-19 residual symptoms significantly decreased, and significant improvements in upper and lower limb muscular strength, cardiopulmonary parameters, perceived physical and mental health, depression and anxiety were observed., Conclusions: The present study confirms the severe physical and psychological impairment of patients with LCS and suggests that a MDR program is effective, safe and feasible in these patients and could promote their physical and psychological recovery., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Ablative and locoregional treatment options, such as radiofrequency, ethanol injection, microwave, and cryoablation, as well as irreversible electroporation, are effective therapies for early-stage hepatocellular carcinoma (HCC). Hepatocyte death caused by ablative procedures is known to increase the release of tumor-associated antigen, thus enhancing tumor immunogenicity. In addition, the heat ablative resection induces pyroptotic cell death accompanied by the release of several inflammatory factors and immune-related proteins, including damage-associated molecular patterns (DAMPs), heat shock proteins (HSPs), ficolin 3, ATP, and DNA/RNA, which potentiate the antitumoral immune response. Surgical approaches that enhance tumor necrosis and reduce hypoxia in the residual liver parenchyma have been shown to increase the disease-free survival rate by reducing the host's immunosuppressive response. Scalpel devices and targeted surgical approach combined with immune-modulating drugs are an interesting and promising area to maximize therapeutic outcomes after HCC ablation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 De Re, Rossetto, Rosignoli, Muraro, Racanelli, Tornesello, Zompicchiatti and Uzzau.)

Introduction: Despite being a life-preserving medical treatment, the demands of haemodialysis are a significant impost on individuals, posing considerable burdens on their work, vocational activities and involvement with family and community. In our region, patients who have had to relocate considerable distances to a regional city for dialysis, and First Nations people, are less likely to attend all scheduled dialysis sessions. Virtual reality (VR) has been shown to improve engagement with care of people on haemodialysis.This manuscript describes the protocol for a cross-over randomised controlled trial (RCT) that will explore the impact of an immersive VR experience for patients attending a northern Queensland, Australia, haemodialysis service., Methods: The design is a crossover RCT, with 8 clusters according to haemodialysis location and schedule. Clusters (5 participants in each) will be randomized by computer program. Participants in the trial will be patients who undergo haemodialysis three times/week at one of two dialysis units. During the 4-week intervention period (12 haemodialysis sessions), participants will be provided a headset with vision representative of the natural environment, and with audio. The 4-week control period will comprise usual activities, such as watching television, reading and sleeping. Outcomes will be measured by participants': attendance at scheduled dialysis sessions; adherence to lifestyle modifications; wellbeing, anxiety and depression; acceptability and usability of VR; and adverse events such as nausea. The feasibility and acceptability of the intervention from clinicians' perspectives will also be explored., Discussion: If this VR intervention is feasible, then participants may engage more with haemodialysis regimens and self-care in this very clinical environment., Trial Registration: ACTRN12621000732886., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2022 Published by Elsevier Inc.)

Background: Children diagnosed with haematological and oncology conditions spend long periods of time undergoing treatments in hospital. Treatments are intensive and may include combinations of chemotherapy, radiation, surgery and bone marrow transplants. This often means that they have prolonged hospital stays away from family, friends and familiar environments., Aim: We aimed at starting an activity group and learning centre based in the hospital setting for children undergoing treatment for haematological and oncology conditions., Methods: The activity group and learning centre was set up in a tertiary care hospital under the department of Paediatric Haematology, Oncology and Bone Marrow Transplantation with the support of a local NGO called 'Samiksha Foundation' in Bangalore, India. Children who participated in the programme engaged in learning through participation in the activity groups which engaged in academic and non-academic activities. The activity group and learning centre was piloted in April and May of 2019. During the pilot sessions, 156 children participated in the group. Children of all ages were welcome to attend and were given activities based on their age and learning levels. Until March 2020, the group has seen over 600 children in attendance., Results: This methods report examines various aspects of the activity group such as setting up of the activity groups, how they are run, the activities conducted in the groups and the effects the group has had on children and their families as reported by them while undergoing treatment., Conclusion: The overall response to the activity groups was positive and widely accepted among our patient community. The intervention proved to be effective, easy to implement and relatively inexpensive. We hope that by sharing data from our centre, more paediatric units may be able to implement such groups for children., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Risk factors for cytomegalovirus (CMV) reactivation and the impact of CMV reactivation on patient outcomes have been extensively investigated after matched related or unrelated donor transplantation, but little is known in the setting of haploidentical stem cell transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy), in which recipients are considered more severely immunocompromised. We retrospectively analyzed a cohort of 554 consecutive patients undergoing Haplo-SCT with PT-Cy at 3 different centers. Early CMV reactivation (occurring within the first 120 days post-transplantation) occurred in 242 patients, for an estimated cumulative incidence of 44%. Among those patients, 74 (30%) had recurrent CMV and 20 (8%) had CMV disease. On multivariable analysis, positive recipient CMV serostatus (hazard ratio [HR] >2.5; P < .001), disease histology (lymphoid versus myeloid: HR, 0.66; P = .003) and increasing recipient age (HR, 1.01; P = .015) were independent predictors of CMV reactivation. At a 4-month landmark analysis, CMV reactivation was associated with higher 1-year and 5-year cumulative incidence of nonrelapse mortality (NRM) relative to patients without reactivation: 13% versus 5% and 22% versus 9%, respectively (P < .001). On multivariable analysis, CMV reactivation was an independent negative predictor of NRM (HR, 2.69; P < .001) and was close to statistically significant for overall survival (HR, 1.38; P = .062). Our results suggest that CMV reactivation plays an important role at determining NRM. Because patient CMV serostatus is the main predictor of CMV reactivation, it should be considered when evaluating strategies for preventing CMV reactivation. 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Trastuzumab is a human epidermal growth factor receptor 2 (HER2) inhibitor used to treat HER2+ metastatic gastric cancer (mGC). The present study aims to investigate the relationship between CDH1 mRNA expression and HER2-positivity in mGC using a multiplexed gene expression profile in two series of gastric cancer (GC): Series 1 ( n = 38): HER2+ and HER2- mGC; Series 2 ( n = 36) HER2- GC with and without metastasis. To confirm the results, the same expression profiles were analyzed in 354 GC from The Cancer Genome Atlas (TCGA) dataset. The difference in gene expression connected HER2 overexpression with canonical wingless-type (Wnt)/β-catenin pathway and immunohistochemical (IHC) expression loss of E-cadherin (E-CAD). CDH1 mRNA expression was simultaneously associated with the rs16260-A variant and an increase in E-CAD expression. Differences in retinoic acid receptor alfa ( RARA ), RPL19 (coding for the 60S ribosomal L19 protein), catenin delta 1 ( CTNND1 ), and epidermal growth factor ( EGF ) mRNA levels-all included in the Wnt/β-catenin pathway-were found associated with overall survival (OS). RARA , CTNND1 , and EGF resulted in independent OS prognostic factors. EGF was confirmed as an independent factor along with TNM stage in HER2-overpressed mGC from TCGA collection. Our study highlighted factors involved in the WNT/β-catenin pathway that interconnected E-CAD with HER2 overexpression and patient survival.

The degree of metastatic disease varies widely among patients with cancer and affects clinical outcomes. However, the biological and functional differences that drive the extent of metastasis are poorly understood. We analyzed primary tumors and paired metastases using a multifluorescent lineage-labeled mouse model of pancreatic ductal adenocarcinoma (PDAC)-a tumor type in which most patients present with metastases. Genomic and transcriptomic analysis revealed an association between metastatic burden and gene amplification or transcriptional upregulation of MYC and its downstream targets. Functional experiments showed that MYC promotes metastasis by recruiting tumor-associated macrophages, leading to greater bloodstream intravasation. Consistent with these findings, metastatic progression in human PDAC was associated with activation of MYC signaling pathways and enrichment for MYC amplifications specifically in metastatic patients. Collectively, these results implicate MYC activity as a major determinant of metastatic burden in advanced PDAC. SIGNIFICANCE: Here, we investigate metastatic variation seen clinically in patients with PDAC and murine PDAC tumors and identify MYC as a major driver of this heterogeneity. This article is highlighted in the In This Issue feature, p. 275 ., (©2021 The Authors; Published by the American Association for Cancer Research.)

Background & Aims: A plethora of second-line therapies have been recently introduced for hepatocellular carcinoma (HCC) treatment with promising results. A meta-analysis of second-line treatments for HCC has been performed to better tailor their use based on improved patient stratification and to identify the best available option., Methods: Pubmed, Scopus, Web of Science, and ClinicalTrials.gov were searched for randomized controlled trials evaluating second-line treatment for advanced HCC in patients already treated with sorafenib. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and drug withdrawal due to adverse events. Network meta-analyses were performed considering placebo as the basis for comparison in efficacy and safety analyses. Subgroup stratification considered gender, age, sorafenib-responsiveness and drug tolerability, viral infection, macrovascular invasion, HCC extrahepatic spread, performance status, and alpha-fetoprotein levels., Results: Fourteen phase II or III randomized controlled trials, involving 5,488 patients and 12 regimens, were included in the analysis. Regorafenib (hazard ratio (HR) = 0.63, 95% confidence interval (CI) = 0.50-0.79), cabozantinib (HR = 0.76, 95% CI = 0.63-0.92), and ramucirumab (HR = 0.82, 95% CI = 0.70-0.76) significantly prolonged OS compared with placebo. Cabozantinib (HR = 0.44, 95% CI = 0.36-0.52), regorafenib (HR = 0.46, 95% CI = 0.37-0.56), ramucirumab (HR = 0.54, 95% CI = 0.43-0.68), brivanib (HR = 0.56, 95% CI = 0.42-0.76), S-1 (HR = 0.60, 95% CI = 0.46-0.77), axitinib (HR = 0.62, 95% CI = 0.44-0.87), and pembrolizumab (HR = 0.72, 95% CI = 0.57-0.90) significantly improved PFS compared with placebo. None of the compared drugs deemed undoubtedly superior after having performed a patients' stratification., Conclusions: The results of this network meta-analysis suggest the use of regorafenib and cabozantinib as second-line treatments in HCC., (© 2021. The Author(s).)