Israel Cancer Association

Chromophobe renal cell carcinoma (ChRCC) is characterized by the accumulation of abnormal mitochondria, a high rate of mitochondrial DNA (mtDNA) mutations, and altered oxidative metabolism. There are no existing circulating biomarkers to distinguish metastatic ChRCC from clear cell renal cell carcinoma (ccRCC). High-throughput plasma proteomic profiling using the SomaScan platform was performed in 18 ChRCC (including 16 metastatic ChRCC) and 197 metastatic ccRCC patients. Data were harmonized to generate a unified 7K-protein matrix. Differential expression analysis was performed using limma (version 3.62.2). Of 7272 quantified human plasma proteins, 209 were differentially expressed between ChRCC and ccRCC. Upregulated proteins in ChRCC included essential β-oxidation enzymes such as ECH1 (enoyl-CoA hydratase 1) and ECI1 (enoyl-CoA delta-isomerase 1), suggesting increased long-chain fatty acid degradation. Creatine and energy-buffering pathways were also represented, with increased CKMT1A (Creatine Kinase, Mitochondrial 1A) in ChRCC. KIM-1 (Kidney Injury Molecule-1) and leptin were lower in ChRCC, consistent with the known upregulation of these proteins in ccRCC. Pathway enrichment analyses revealed an overrepresentation of mitochondrial protein degradation, fatty acid β-oxidation, and respiratory electron transport in ChRCC, suggesting that ChRCC sheds a unique mitochondrial signature into the peripheral circulation. A bootstrap-based LASSO logistic regression restricted to upregulated mitochondrial proteins in ChRCC vs. ccRCC consistently selected ECI1 and CKMT1A. The LASSO model achieved an AUROC of 0.964. Compared to ccRCC, the plasma proteome of metastatic ChRCC is dominated by mitochondrial metabolic enzymes, revealing a systemic metabolic phenotype strikingly aligned with the known histologic accumulation of abnormal mitochondria in ChRCC cells.

Nest sanitation is thought to be an important component of reproductive success because it can reduce pathogen loads and ectoparasites in the nest. Coprophagy – the ingestion of faeces – includes consumption of nestling faecal sacs by adults (allocoprophagy) and is therefore often discussed in the context of sanitation. In several bird taxa, this behaviour has also been linked to the “parental nutrition hypothesis”, whereby adults may recover part of the energetic and nutritional costs of provisioning. In the Common Swift (Apus apus), faecal sac ingestion has been documented, yet the energetic content of faecal sacs has rarely been quantified directly, limiting evaluation of potential energetic recycling. Here we quantify the energy content of nestling faecal sacs using bomb calorimetry and test how gross energy relates to sac mass while describing among-nest variation. We collected 224 faecal sacs from nine nests in central Israel after fledging and measured gross energy and (desiccated) mass of each sample. Mean gross energy was 1.94 kJ per sac, with substantial variation among nests. In a mixed-effects model, gross energy increased with sac mass, and sacs from the same nest were more similar in energy content to each other than to sacs from other nests. Because samples were collected post-fledging and we did not measure ingestion frequency or assimilation efficiency, our results quantify the gross energetic substrate potentially available for recycling, but do not by themselves demonstrate a net energetic benefit of coprophagy. We outline the need for studies linking faecal-sac energy to nestling age, provisioning dynamics, and adult energy budgets to evaluate ecological payoffs and potential selection on this behaviour.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-026-40366-0.

<bold>Background:</bold> Several biologic treatments are available for asthma patients who are not well controlled with inhaled corticosteroids (ICS) and bronchodilators. Anti-IgE (omalizumab) and anti-IL-5 (mepolizumab, dupilumab, omalizumab and reslizumab). Real-life studies that compare the effectiveness of add-on biologic treatment are lacking. <bold>Methods:</bold> The study population were adult asthma patients who treated with omalizumab and mepolizumab for asthma alone. The number of systemic steroids (injectable and oral) and the number of ICS purchases were compered between 12 months before the first biological treatment and 12 months after. <bold>Results:</bold> Of the 173 patients, 122 were treated with omalizumab and 51 with mepolizumab. There was no significant difference in the mean age between the two groups. Higher proportion of females received mepolizumab than omalizumab (75% vs. 57%, p = 0.0339). Omalizumab significantly reduces the number of patients who purchases steroid tablets from 34% to 20% (p < 0.001) but not mepolizumab. No significant differences were found in the number of patients who purchased steroid tablets or inhalers between the year before and during the biological treatments for both drugs. For both drugs, no significant differences were found in the mean number of steroid injections, tablets and inhaler purchase during the year of biological treatments among patients who purchased them at a year before. <bold>Conclusion:</bold> Omalizumab in this study was superior to mepolizumab in reducing the number of patients who were treated with steroid injections. This call for randomized control trail to further explore the effectiveness of different biological treatments in asthma.

Introduction/BackgroundWe aimed to assess the awareness of healthy women who present online to endometrial cancer (EC) symptoms and risk factors among the Israeli population.MethodologyA survey regarding awareness of EC symptoms and risk factors was published in secure link on popular Israeli feminine social-media groups (>20,000 users), for accurate reach. The survey was conducted during May 2023 just before establishing June as Uterine Cancer Awareness Month. 1161 healthy women completed the survey voluntarily and anonymously.ResultsThousand-fifty-six women met the survey’s inclusion criteria. About 90% graduated college, all graduated high-school. The respondents were predominantly non-orthodox Jewish. More than quarter had a healthcare background.About two-thirds visit gynecologist at least once a year and about three-quarters had a gynecological examination in the last year.Most respondents were aware of other gynecological cancers, mainly cervical and ovarian cancers. Only about a quarter of the survey population had some awareness of EC symptoms. Nearly half of study population had some idea about signs and symptoms of any gynecological cancer.Regarding EC, more than a quarter were unaware of vaginal bleeding as an EC symptom and about 90% were unaware of any EC risk factors. More than three-quarters were defined as unaware at all. Only about 1% were fully aware. A statistical trend was observed as women older than 45 were more aware than younger. If a symptom occurs, most declared they would visit a gynecologist and only about 8% would refer to their general-practitioner.ConclusionIn our study population, we observed an extremely-low awareness of the most common gynecological cancer in the industrial world (EC) which has easily diagnosed symptoms and risk factors. This striking findings, in a highly-educated and media-exposed group, are a wakeup-call for policymakers and regulators to take further action in order to achieve earlier diagnosis and curative prognosis in EC patients.DisclosuresNo conflict of interest declared, no study funding declared.

304 Background: Cervical cancer patients' age is relatively young (considering only 35-39 and not 60-64). In this young age, patient might consider birth planning and other sexual health considerations such as vaginal rehabilitation. Methods: A call for answers to a survey was published and patients and verified survivors were invited to respond voluntarily and anonymously through a coded and encrypted web form. Results: 116 women responded to the survey (age 21-72, median=42, age range at diagnosis 18-65). 8% were diagnosed with CIN1-2, 43% with CIN3, 20% with stage 1, 7% with stage 2, 10% with stages 3-4, 12% didn't know how to answer. Past treatments were recorded. 84% of those required to perform vaginal dilator did not do so (results were modified in accordance to guidelines). At childbearing age [67 women, ages 21-45, median=37; 55.22% CIN3, 19.4% stage 1, 5.97% stage 2, 5.97% stages 3-4, 13.43% didn't know how to answer; 77.61% are sexually active with singular known partner], only 58.2% recall having a discussion with their physician regarding fertility preservation, before beginning of treatments. 32.83% recall such a discussion afterwards. 11.94% give birth after illness or had a child thanks to a surrogate mother. Conclusions: This study underscores the need for greater attention to patients’ sexual health and fertility aspects before and after completion of treatments. There is a need in coordinate patients' expectations regarding birth planning and in making the information regarding vaginal dilator accessible. Research involving a larger sample size may help to better support the information needs of survivors.

Regulatory molecules have recently been recognized for their beneficial effects in the treatment of immune-mediated diseases, rather than using cytotoxic immune-suppressing drugs, which are associated with many unwanted side effects. Semaphorin3A (sema3A), a unique regulatory master of the immune system, was shown to be decreased in the serum of systemic lupus erythematosus (SLE) patients, in association with disease severity. Later, we were able to show its extremely beneficial effect in treating lupus nephritis in the NZB/W mice model. The mechanisms by which sema3A maintains its regulatory effect is by binding the regulatory receptor CD72 on B cells, thereby reducing the threshold of BCR signaling on B cells and reducing the production of pro-inflammatory cytokines. The aim of this study was to generate a stable sema3A molecule, easy to produce with a higher binding capacity to CD72 receptor rather than to Neuropilin-1 (NRP-1) receptor, which is expressed in many cell types. Using the crystallographic structure of parental sema3A, we synthesized a new secreted (shorter) sema3A derivative, which we called truncated sema3A (T-sema3A). The new molecule lacked the NRP-1 binding domain (the C-terminal site) and has an artificial dimerization site at position 257 (serine residue was exchanged with a cysteine residue). To facilitate the purification of this molecule we added Histidine epitope tag in frame upstream to a stop codon. This construct was transfected using a viral vector to 293HEK cells to generate cells stably expressing T-sema3A. T-sema3A is shown to be with a higher binding ability to CD72 than to NRP-1 as demonstrated by a homemade ELISA. In addition, T-sema3A was shown to be a regulatory agent which can induce the expression of IL-10 and TGF-β and reduce the secretion of pro-inflammatory cytokines such as IL-6, IFN-γ, and IL-17A from human T and B-lymphocytes. Keeping this in mind, T-sema3A is highly effective in maintaining immune homeostasis, therefore, becoming a potential agent in restoring the regulatory status of the immune system in immune-mediated diseases.

Key summary pointsAimTo explore current deprescribing attitudes and practices among geriatricians and geriatricians-in-training across Europe.FindingsFunctional decline, adverse drug reactions and adherence to guidelines/checklists for managing polypharmacy were the most important reasons for deprescribing. The most important barriers for deprescribing were patients’ unwillingness, fear of negative consequences, lack of time, and poor communication between multiple prescribers. Only one in four respondents thought education in medical school had sufficiently prepared them for deprescribing in clinical practice.MessageThere is a need for improved inter-professional communication, better education and evidence-based recommendations to improve future person-centered prescribing and resultant deprescribing practices.

A small but significant proportion of COVID‐19 patients develop life‐threatening cytokine storm. We have developed a new anti‐inflammatory drug, EXO‐CD24, a combination of an immune checkpoint (CD24) and a delivery platform (exosomes). CD24 inhibits the NF‐kB pathway and the production of cytokines/chemokines. EXO‐CD24 discriminates damage‐from pathogen‐associated molecular patterns (DAMPs and PAMPs) therefore does not interfere with viral clearance. EXO‐CD24 was produced and purified from CD24‐expressing 293‐TREx™ cells. Exosomes displaying murine CD24 (mCD24) were also created. EXO‐CD24/mCD24 were characterized and examined, for safety and efficacy, in vitro and in vivo. In a phase Ib/IIa study, 35 patients with moderate–high severity COVID‐19 were recruited and given escalating doses, 108–1010, of EXO‐CD24 by inhalation, QD, for 5 days. No adverse events related to the drug were observed up to 443–575 days. EXO‐CD24 effectively reduced inflammatory markers and cytokine/chemokine, although randomized studies are required. EXO‐CD24 may be a treatment strategy to suppress the hyper‐inflammatory response in the lungs of COVID‐19 patients and further serve as a therapeutic platform for other pulmonary and systemic diseases characterized by cytokine storm.

There is increasing evidence for the effectiveness of behavioral techniques in managing tics in youth with Tourette syndrome and tics disorders (TDs). One such intervention is Comprehensive Behavioral Intervention for Tics (CBIT), which focuses on reducing tic severity by training control and regulation. In view of the regulation deficits characteristic to TDs, in the current study, we aimed to explore the contribution of CBIT beyond tic control, to a wider expression of regulation abilities-cognitive inhibition and emotion regulation. A total of 55 participants with TDs, aged 8-15, who were randomly assigned to group-CBIT or group-Educational Intervention for Tics, were compared on cognitive inhibition tests and use of emotion-regulation strategies, pre- and post-intervention. Whereas on none of the scales a significant interactioneffect was found reflecting superiority of CBIT over EIT, repeated measures ANOVA revealed a significant time effect, with post hoc analyses indicating that cognitive inhibition and cognitive reappraisal significantly increased following CBIT intervention only. Within the group-CBIT, the increase in cognitive reappraisal was associated with higher intellectual ability. These findings may lead to a broader understanding of CBIT contribution to more than tic control, but rather to better cognitive and emotional regulation abilities.