Selective targeting of Plasmodium falciparum Hsp90 disrupts the 26S proteasome.

The molecular chaperone heat shock protein 90 (Hsp90) has an essential but largely undefined role in maintaining proteostasis in Plasmodium falciparum, the most lethal malaria parasite. Herein, we identify BX-2819 and XL888 as potent P. falciparum (Pf)Hsp90 inhibitors. Derivatization of XL888's scaffold led to the development of Tropane 1, as a PfHsp90-selective binder with nanomolar affinity. Hsp90 inhibitors exhibit anti-Plasmodium activity against the liver, asexual blood, and early gametocyte life stages. Thermal proteome profiling was implemented to assess PfHsp90-dependent proteome stability, and the proteasome-the main site of cellular protein recycling-was enriched among proteins with perturbed stability upon PfHsp90 inhibition. Subsequent biochemical and cellular studies suggest that PfHsp90 directly promotes proteasome hydrolysis by chaperoning the active 26S complex. These findings expand our knowledge of the PfHsp90-dependent proteome and protein quality control mechanisms in these pathogenic parasites, as well as further characterize this chaperone as a potential antimalarial drug target.

The prevalence of non-contrast CT imaging abnormalities in reversible cerebral vasoconstriction syndrome: A systematic review and meta-analysis.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is a syndrome of recurrent thunderclap headaches and reversible vasoconstriction of the cerebral arteries on neuroimaging within 3 months of onset. Initial non-contrast computed tomography (CT) can reveal abnormalities such as ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage (SAH) can be present in patients with RCVS and may delay diagnosis. AIMS: We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. We aimed to estimate the prevalence of imaging abnormalities on initial non-contrast CT head in adult patients with RCVS. DATA SOURCES & ELIGIBILITY CRITERIA: We searched electronic databases including MEDLINE, EMBASE, and the Cochrane Register of Clinical Trials from inception to August 2, 2022. Eligible studies included articles reporting the prevalence of non-contrast CT abnormalities on initial neuroimaging in patients with RCVS, aged 18 and older. Case series, observational studies and clinical trials were included. Data was extracted directly from included papers using a standardized data charting form. RESULTS: The search yielded 722 titles with duplicates removed. Twenty studies that included 379 patients with RCVS met inclusion criteria. We classified non-contrast CT abnormalities as either ischemic stroke, ICH, or SAH. We pooled prevalence data using a random effects model with the inverse-variance weighted method. The most common imaging finding was SAH with a pooled prevalence of 24% (95% CI:17%-33%), followed by ICH at 14% (95% CI:8%-22%), and ischemic stroke at 10% (95% CI:7%-14%). The pooled prevalence of any of these imaging abnormalities on initial non-contrast CT was 31% (95% CI:23%-40%). Risk of bias was moderate to very-high-risk for case-series and low-risk for observational studies. CONCLUSION: Our review demonstrates that one-third of patients with RCVS will have an abnormality on initial non-contrast CT head, including either an ischemic stroke, ICH, or SAH. These findings highlight the diagnostic challenges of RCVS imaging and contribute to our understanding of this disease.

An expanded transcriptome atlas for Bacteroides thetaiotaomicron reveals a small RNA that modulates tetracycline sensitivity.

Plasticity in gene expression allows bacteria to adapt to diverse environments. This is particularly relevant in the dynamic niche of the human intestinal tract; however, transcriptional networks remain largely unknown for gut-resident bacteria. Here we apply differential RNA sequencing (RNA-seq) and conventional RNA-seq to the model gut bacterium Bacteroides thetaiotaomicron to map transcriptional units and profile their expression levels across 15 in vivo-relevant growth conditions. We infer stress- and carbon source-specific transcriptional regulons and expand the annotation of small RNAs (sRNAs). Integrating this expression atlas with published transposon mutant fitness data, we predict conditionally important sRNAs. These include MasB, which downregulates tetracycline tolerance. Using MS2 affinity purification and RNA-seq, we identify a putative MasB target and assess its role in the context of the MasB-associated phenotype. These data-publicly available through the Theta-Base web browser ( http://micromix.helmholtz-hiri.de/bacteroides/ )-constitute a valuable resource for the microbiome community.

Syphilis Prevalence, Incidence, and Demographic Differences in a Longitudinal Study of Young Sexual and Gender Minority Adults Assigned Male at Birth.

BACKGROUND: Syphilis rates in the United States have increased. Few studies have examined syphilis incidence and prevalence prospectively among young sexual and gender minorities (YSGM). METHODS: This study of YSGM assigned male at birth comes from a Chicago-based prospective cohort at 2 visits 6 months apart (N = 882). Syphilis cases were identified through serologic test results and self-reported history. RESULTS: In this sample, 25.1% had a lifetime prevalence, and 3.3% were incident cases with a crude incidence rate of 6.76 per 100 person-years. CONCLUSIONS: Lifetime syphilis and incidence are high in this sample of YSGM relative to general population samples.

Predicting Problematic Behavior in Autism Spectrum Disorder Using Medical History and Environmental Data.

Autism spectrum disorder (ASD), characterized by social, communication, and behavioral abnormalities, affects 1 in 36 children according to the CDC. Several co-occurring conditions are often associated with ASD, including sleep and immune disorders and gastrointestinal (GI) problems. ASD is also associated with sensory sensitivities. Some individuals with ASD exhibit episodes of challenging behaviors that can endanger themselves or others, including aggression and self-injurious behavior (SIB). In this work, we explored the use of artificial intelligence models to predict behavior episodes based on past data of co-occurring conditions and environmental factors for 80 individuals in a residential setting. We found that our models predict occurrences of behavior and non-behavior with accuracies as high as 90% for some individuals, and that environmental, as well as gastrointestinal, factors are notable predictors across the population examined. While more work is needed to examine the underlying connections between the factors and the behaviors, having reasonably accurate predictions for behaviors has the potential to improve the quality of life of some individuals with ASD.

Urine point-of-care tenofovir test demonstrates strong predictive clinical and research utility.

BACKGROUND: Preexposure prophylaxis (PrEP) significantly reduces HIV infection risk but is dependent on adherence. Available approaches to measuring adherence have limitations related to accuracy, cost, practicality, and timeliness. This study compared the performance of two methods implementable in clinics and research studies [interview and urine point of care (POC) assay] to the gold-standard for measuring recent and longer term adherence in dried blood spots (DBS). METHODS: Participants were recruited from RADAR, a cohort study of young MSM, or via online advertisements. At 3 monthly visits, an interviewer administered 7-day timeline follow-back (TLFB) questionnaire, DBS samples were tested for tenofovir-diphosphate (TFV-DP) to estimate average dosing over the prior month and emtricitabine-triphosphate (FTC-TP) to assess recent dosing (past 2-3 days), and a urine POC TFV test to qualitatively assess recent adherence (past 4 days). RESULTS: Eighty-three PrEP users contributed 163 observations. At visit 1, self-reported adherence was 86% (4+ doses in last 7 days), versus urine TFV (74%), DBS FTC-TP (76%), and DBS TFV-DP (69%). The objective measures of short-term adherence performed similarly well in predicting longer term adherence. In multivariable logistic regression analyses, the urine assay was a significant predictor of DBS TFV-DP (adjusted OR = 19.4, P  < 0.0001); self-report did not add significantly. CONCLUSION: The urine POC TFV assay had excellent predictive values for adherence and self-report did not add significantly to prediction. The POC assay provides results in several minutes to enable same-visit counseling, requires no specialized training, and is projected to be low-cost.

Let-7 enhances murine anti-tumor CD8 T cell responses by promoting memory and antagonizing terminal differentiation.

The success of the CD8 T cell-mediated immune response against infections and tumors depends on the formation of a long-lived memory pool, and the protection of effector cells from exhaustion. The advent of checkpoint blockade therapy has significantly improved anti-tumor therapeutic outcomes by reversing CD8 T cell exhaustion, but fails to generate effector cells with memory potential. Here, using in vivo mouse models, we show that let-7 miRNAs determine CD8 T cell fate, where maintenance of let-7 expression during early cell activation results in memory CD8 T cell formation and tumor clearance. Conversely, let-7-deficiency promotes the generation of a terminal effector population that becomes vulnerable to exhaustion and cell death in immunosuppressive environments and fails to reject tumors. Mechanistically, let-7 restrains metabolic changes that occur during T cell activation through the inhibition of the PI3K/AKT/mTOR signaling pathway and production of reactive oxygen species, potent drivers of terminal differentiation and exhaustion. Thus, our results reveal a role for let-7 in the time-sensitive support of memory formation and the protection of effector cells from exhaustion. Overall, our data suggest a strategy in developing next-generation immunotherapies by preserving the multipotency of effector cells rather than enhancing the efficacy of differentiation.

The Sexual Orientation Microaggression Inventory Short Form (SOMI-SF): Validation in Three Samples of Racially/Ethnically Diverse Sexual Minority Youth.

Introduction: The Sexual Orientation Microaggression Inventory (SOMI) has been used to measure sexual orientation-based microaggression experiences. However, at 19 items, the SOMI may be difficult to fit into survey batteries where microaggressions are not the primary predictor or the time researchers have with each participant is very limited. Methods: We sought to identify an eight-item short form of the SOMI (SOMI-SF) in a sample of sexual minority (SM) youth (N = 879) and confirm the validity and reliability of the SOMI-SF by administering both versions to separate cohorts of male-assigned (N = 533) and female-assigned (N = 430) at birth SM youth. Data was collected from April 2018 to May 2020. Results: We found high reliability (α > 0.80) and validity (significant association with SM victimization, depression symptoms, anxiety symptoms, and internalized stigma) in all three samples for the SOMI-SF. Conclusions: For researchers looking to conserve time and limit burden, the SOMI-SF is a high quality option for measuring sexual orientation microaggressions. Policy Implications: The greater ease of administering the SOMI-SF means that sexual orientation microaggressions can be measured in a greater number of contexts. With a growing literature linking these experiences to poorer health outcomes for SM populations, measuring these experiences quickly and accurately can improve our understanding of the mechanisms creating those links and impact policy necessary to alleviate them.

Protein Tyrosine Phosphatase Non-Receptor 11 (PTPN11/Shp2) as a Driver Oncogene and a Novel Therapeutic Target in Non-Small Cell Lung Cancer (NSCLC).

PTPN11 encodes the SHP2 protein tyrosine phosphatase that activates the mitogen-activated protein kinase (MAPK) pathway upstream of KRAS and MEK. PTPN11/Shp2 somatic mutations occur frequently in Juvenile myelomonocytic leukaemia (JMML); however, the role of mutated PTPN11 in lung cancer tumourigenesis and its utility as a therapeutic target has not been fully addressed. We applied mass-spectrometry-based genotyping to DNA extracted from the tumour and matched the normal tissue of 356 NSCLC patients (98 adenocarcinomas (LUAD) and 258 squamous cell carcinomas (LUSC)). Further, PTPN11 mutation cases were identified in additional cohorts, including TCGA, Broad, and MD Anderson datasets and the COSMIC database. PTPN11 constructs harbouring PTPN11 E76A, A72D and C459S mutations were stably expressed in IL-3 dependent BaF3 cells and NSCLC cell lines (NCI-H1703, NCI-H157, NCI-H1299). The MAPK and PI3K pathway activation was evaluated using Western blotting. PTPN11/Shp2 phosphatase activity was measured in whole-cell protein lysates using an Shp2 assay kit. The Shp2 inhibitor (SHPi) was assessed both in vitro and in vivo in a PTPN11-mutated cell line for improved responses to MAPK and PI3K targeting therapies. Somatic PTPN11 hotspot mutations occurred in 4/98 (4.1%) adenocarcinomas and 7/258 (2.7%) squamous cells of 356 NSCLC patients. Additional 26 PTPN11 hotspot mutations occurred in 23 and 3 adenocarcinomas and squamous cell carcinoma, respectively, across the additional cohorts. Mutant PTPN11 significantly increased the IL-3 independent survival of Ba/F3 cells compared to wildtype PTPN11 (p < 0.0001). Ba/F3, NCI-H1703, and NCI-H157 cells expressing mutant PTPN11 exhibited increased PTPN11/Shp2 phosphatase activity and phospho-ERK1/2 levels compared to cells expressing wildtype PTPN11. The transduction of the PTPN11 inactivating mutation C459S into NSCLC cell lines led to decreased phospho-ERK, as well as decreased phospho-AKT in the PTPN11-mutated NCI-H661 cell line. NCI-H661 cells (PTPN11-mutated, KRAS-wild type) were significantly more sensitive to growth inhibition by the PI3K inhibitor copanlisib (IC50: 13.9 ± 4.7 nM) compared to NCI-H1703 (PTPN11/KRAS-wild type) cells (IC50: >10,000 nM). The SHP2 inhibitor, in combination with the PI3K targeting therapy copanlisib, showed no significant difference in tumour development in vivo; however, this significantly prevented MAPK pathway induction in vitro (p < 0.0001). PTPN11/Shp2 demonstrated the in vitro features of a driver oncogene and could potentially sensitize NSCLC cells to PI3K inhibition and inhibit MAPK pathway activation following PI3K pathway targeting.

Stress and Depression Are Associated with Sexual Function and Satisfaction in Young Men Who Have Sex with Men.

Prior research suggests that better mental health and higher relationship quality are associated with better sexual function and satisfaction. Such insights can inform intervention development for mental, relationship, and sexual health concerns. This study examined the interactions among these variables in a racially and ethnically diverse group of young men who have sex with men (YMSM) in serious relationships (N = 348). Data were drawn from wave 5 of a longitudinal cohort study. We examined cross-sectional associations between depression and stress (predictors) and sexual function, sexual satisfaction, and anal discomfort (outcomes) and to what extent these associations were moderated by relationship quality. Higher endorsement of depression and stress was associated with worse sexual functioning, lower sexual satisfaction, and more anal discomfort. We also found that fewer negative interactions, stronger commitment, and higher relationship satisfaction were associated with better sexual functioning and higher sexual satisfaction. Higher relationship satisfaction and commitment were found to attenuate the association between stress and sexual satisfaction. Contrary to expectations, higher relationship satisfaction also showed a trend toward exacerbating the association between depression and sexual functioning. These results suggest that, for YMSM, high relationship satisfaction and commitment may protect sexual satisfaction from being negatively impacted by high stress. However, YMSM in highly satisfying relationships may experience poor sexual functioning associated with depression as particularly distressing. This study addressed a major gap in the literature by focusing on mental, relationship, and sexual health in a diverse sample. Future research should examine a wider range of sexual functioning outcomes and include minority stress in study design.

Frequency of inter-specialty consensus decisions and adherence to advice following discussion at a weekly neurovascular multidisciplinary meeting.

BACKGROUND/AIMS: Data are limited on the frequency of 'consensus decisions' between sub-specialists attending a neurovascular multidisciplinary meeting (MDM) regarding management of patients with extracranial carotid/vertebral stenoses and post-MDM 'adherence' to such advice. METHODS: This prospective audit/quality improvement project collated prospectively-recorded data from a weekly Neurovascular/Stroke Centre MDM documenting the proportion of extracranial carotid/vertebral stenosis patients in whom 'consensus management decisions' were reached by neurologists, vascular surgeons, stroke physicians-geriatricians and neuroradiologists. Adherence to MDM advice was analysed in asymptomatic carotid stenosis (ACS), symptomatic carotid stenosis (SCS), 'indeterminate symptomatic status stenosis' (ISS) and vertebral artery stenosis (VAS) patients, including intervals between index event to MDM + / - intervention. RESULTS: One hundred fifteen patients were discussed: 108 with carotid stenosis and 7 with VAS. Consensus regarding management was noted in 96.5% (111/115): 100% with ACS and VAS, 96.2% with SCS and 92.9% with ISS. Adherence to MDM management advice was 96.4% (107/111): 100% in ACS, ISS and VAS patients; 92% (46/50) in SCS patients. The median interval from index symptoms to revascularisation in 50-99% SCS patients was 12.5 days (IQR: 9-18.3 days; N = 26), with a median interval from MDM to revascularisation of 5.5 days (IQR: 1-7 days). Thirty patients underwent revascularisation. Two out of twenty-nine patients (6.9%) with either SCS or ISS had a peri-procedural ipsilateral ischaemic stroke, with no further strokes/deaths during 3-months follow-up. CONCLUSIONS: The high frequency of inter-specialty consensus regarding management and adherence to proposed treatment supports a collaborative/multidisciplinary model of care in patients with extracranial arterial stenoses. Service development should aim to shorten times between MDM discussion-intervention and optimise prevention of stroke/death.

A Retrospective Analysis of Distal Fibula Fractures Treated With Intramedullary Fibular Nail Fixation.

There is growing literature supporting the use of intramedullary fixation for fracture care because of its smaller incisions, improved biomechanical outcomes, and faster time to weightbearing than traditional internal fixation methods. The aim of this study is to investigate the postoperative outcomes in ankle fractures treated with intramedullary nail fixation in the largest patient cohort to date. From 2015 to 2021, 151 patients were evaluated following surgical treatment of fibular fractures with intramedullary nail fixation. Patients were identified through a medical record database search for appropriate ankle fracture procedure codes. Patient information was reviewed for fracture type, adjunct procedures, time to weightbearing and postoperative complications. Radiographs were assessed for quality and time to radiographic union. The mean time to weightbearing was 4.8 weeks. Minor wound dehiscence was identified in 2 patients (1.3%). Superficial infection was present in 4 patients (2.6%) and a deep infection developed in 2 patients (1.3%). Two patients developed a nonunion (1.5%). There were no DVTs reported, although 1 patient developed a PE postoperatively. Radiographic quality of reduction and time to union is comparable to literature reported plate and screw construct outcomes. Reduction was classified as good in 86.1% of patients and radiographic union was appreciated in 98.5% of patients. This is the largest cohort study evaluating the outcomes of intramedullary nail fixation for ORIF of ankle fractures. These data reinforce that intramedullary nailing provides a minimally invasive approach with accurate anatomic reduction, excellent fracture union rates, low complication rates, and an early return to weightbearing.

The Current State of Functional MR Imaging for Trauma Prognostication.

In this review, we discuss the basics of functional MRI (fMRI) techniques including task-based and resting state fMRI, and overview the major findings in patients with traumatic brain injury. We summarize the studies that have longitudinally evaluated the changes in brain connectivity and task-related activation in trauma patients during different phases of trauma. We discuss how these data may potentially be used for prognostication, treatment planning, or monitoring and management of trauma patients.

An integrated transcriptomics-functional genomics approach reveals a small RNA that modulates Bacteroides thetaiotaomicron sensitivity to tetracyclines.

Gene expression plasticity allows bacteria to adapt to diverse environments, tie their metabolism to available nutrients, and cope with stress. This is particularly relevant in a niche as dynamic and hostile as the human intestinal tract, yet transcriptional networks remain largely unknown in gut Bacteroides spp. Here, we map transcriptional units and profile their expression levels in Bacteroides thetaiotaomicron over a suite of 15 defined experimental conditions that are relevant in vivo , such as variation of temperature, pH, and oxygen tension, exposure to antibiotic stress, and growth on simple carbohydrates or on host mucin-derived glycans. Thereby, we infer stress- and carbon source-specific transcriptional regulons, including conditional expression of capsular polysaccharides and polysaccharide utilization loci, and expand the annotation of small regulatory RNAs (sRNAs) in this organism. Integrating this comprehensive expression atlas with transposon mutant fitness data, we identify conditionally important sRNAs. One example is MasB, whose inactivation led to increased bacterial tolerance of tetracyclines. Using MS2 affinity purification coupled with RNA sequencing, we predict targets of this sRNA and discuss their potential role in the context of the MasB-associated phenotype. Together, this transcriptomic compendium in combination with functional sRNA genomics-publicly available through a new iteration of the 'Theta-Base' web browser (www.helmholtz-hiri.de/en/datasets/bacteroides-v2)-constitutes a valuable resource for the microbiome and sRNA research communities alike.

An evaluation on the effects of safe person handling program implementation at long term care facilities for persons with complex intellectual, developmental, and medical conditions.

BACKGROUND: This retrospective chart review sought to determine whether the introduction of a safe person handling and mobility (SPHM) program resulted in changes to the frequency, severity, cost, or profile of staff injuries incurred during person handling (PH) tasks at long-term care settings for persons with complex conditions. METHODS: This study analyzed the SPHM program implementation at an organization providing long-term residential, day habilitation, and special education services for persons with complex conditions. Data covered two 4-year periods before and after implementation. Analyses compared the frequency, severity, and cost of staff PH injuries, as well as of the affected body area, staff role, level of treatment, and the incurred costs of Workers' Compensation (WC) claims. RESULTS: There were substantive decreases in the total number of staff PH injuries and WC claims. Staff PH injuries affecting the trunk, the area most associated with PH injuries, decreased the most, followed by the upper extremities. Reductions were concentrated among direct care employees and their supervisors, job titles where PH exposures are most commonly seen. The proportion of staff injuries requiring medical treatment decreased significantly, as did injury severity. The number of lost workdays decreased by 94.6%. Incurred WC costs decreased by 91.1%. The proportion of WC claims associated with lost time decreased significantly. CONCLUSIONS: Substantive reductions in the frequency, severity, and incurred WC cost of staff PH injuries followed implementation of the SPHM program. Likewise, proportional changes were identified among the programs where cases occurred, the need for medical treatment, and WC cost type.

Pleural fluid microbiota as a biomarker for malignancy and prognosis.

Malignant pleural effusions (MPE) complicate malignancies and portend worse outcomes. MPE is comprised of various components, including immune cells, cancer cells, and cell-free DNA/RNA. There have been investigations into using these components to diagnose and prognosticate MPE. We hypothesize that the microbiome of MPE is unique and may be associated with diagnosis and prognosis. We compared the microbiota of MPE against microbiota of pleural effusions from non-malignant and paramalignant states. We collected a total of 165 pleural fluid samples from 165 subjects; Benign (n = 16), Paramalignant (n = 21), MPE-Lung (n = 57), MPE-Other (n = 22), and Mesothelioma (n = 49). We performed high throughput 16S rRNA gene sequencing on pleural fluid samples and controls. We showed that there are compositional differences among pleural effusions related to non-malignant, paramalignant, and malignant disease. Furthermore, we showed differential enrichment of bacterial taxa within MPE depending on the site of primary malignancy. Pleural fluid of MPE-Lung and Mesothelioma were associated with enrichment with oral and gut bacteria that are commonly thought to be commensals, including Rickettsiella, Ruminococcus, Enterococcus, and Lactobacillales. Mortality in MPE-Lung is associated with enrichment in Methylobacterium, Blattabacterium, and Deinococcus. These observations lay the groundwork for future studies that explore host-microbiome interactions and their influence on carcinogenesis.

Rapid Multivariate Analysis Approach to Explore Differential Spatial Protein Profiles in Tissue.

Spatially targeted proteomics analyzes the proteome of specific cell types and functional regions within tissue. While spatial context is often essential to understanding biological processes, interpreting sub-region-specific protein profiles can pose a challenge due to the high-dimensional nature of the data. Here, we develop a multivariate approach for rapid exploration of differential protein profiles acquired from distinct tissue regions and apply it to analyze a published spatially targeted proteomics data set collected from Staphylococcus aureus-infected murine kidney, 4 and 10 days postinfection. The data analysis process rapidly filters high-dimensional proteomic data to reveal relevant differentiating species among hundreds to thousands of measured molecules. We employ principal component analysis (PCA) for dimensionality reduction of protein profiles measured by microliquid extraction surface analysis mass spectrometry. Subsequently, k-means clustering of the PCA-processed data groups samples by chemical similarity. Cluster center interpretation revealed a subset of proteins that differentiate between spatial regions of infection over two time points. These proteins appear involved in tricarboxylic acid metabolomic pathways, calcium-dependent processes, and cytoskeletal organization. Gene ontology analysis further uncovered relationships to tissue damage/repair and calcium-related defense mechanisms. Applying our analysis in infectious disease highlighted differential proteomic changes across abscess regions over time, reflecting the dynamic nature of host-pathogen interactions.

The mosquito effect: regulatory and effector T cells acquire cytoplasmic material from tumor cells through intercellular transfer.

The phenomenon of intercellular transfer of cellular material, including membranes, cytoplasm, and even organelles, has been observed for decades. The functional impact and molecular mechanisms of such transfer in the immune system remain largely elusive due to the absence of a robust in vivo model. Here, we introduce a new tumor mouse model, where tumor cells express the soluble ultra-bright fluorescent protein ZsGreen, which allows detection and measurement of intercellular transfer of cytoplasm from tumor cells to infiltrating immune cells. We found that in addition to various types of myeloid lineage cells, a large fraction of T regulatory cells and effector CD8 T cells acquire tumor material. Based on the distribution of tumor-derived ZsGreen, the majority of T cells integrate captured cytoplasm into their own, while most myeloid cells store tumor material in granules. Furthermore, scRNA-seq analysis revealed significant alterations in transcriptomes of T cells that acquired tumor cell cytoplasm, suggesting potential impact on T cell function. We identified that the participation of T cells in intercellular transfer requires cell-cell contact and is strictly dependent on the activation status of T lymphocytes. Finally, we propose to name the described phenomenon of intercellular transfer for tumor infiltrating T cells the "mosquito effect".