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Glioblastoma stem cells (GSCs) are key drivers of relapse, metastasis, and therapy resistance in glioblastoma due to their adaptability and diversity, which make them challenging to target effectively. This study explores the O-glycosylation in differentiating two key GSC subtypes, CD133 and CD44. We utilized the TCGA dataset of GBM and presented the reproducible bioinformatics analysis for our results. Our profiling showed enriched O-glycosylation signatures in CD44-expressing GBM cells over CD133, with Cosmc, the chaperone for core mucin-type O-glycosylation, significantly upregulated in the CD44-positive group. Moreover, Cosmc was associated with shorter progression-free intervals, suggesting its potential as an indicator of aggressive disease. High Cosmc expression also enriched immune-related pathways, including inflammatory response and antigen presentation, and was associated with presence of myeloid cells, T cells, and NK cells. Additionally, elevated Cosmc correlated with extracellular matrix (ECM) pathways and stromal cell populations, such as perivascular fibroblasts. These findings position O-glycosylation, specially, Cosmc as a promising biomarker for distinguishing GSC subclones, with relevance to immune modulation, and ECM dynamics, identifying it as a potential target for novel GBM therapies.

Glioblastoma multiforme (GBM) represents the deadliest form of brain cancer, characterized by complex interactions within its microenvironment. Despite the understanding of GBM biology, GBM remains highly resistant to any therapy. Therefore, defining innovative biomarkers in GBM can provide insights into tumor biology and potential therapeutic targets. In this study, we explored the potential of GPRC5A to serve as a pertinent biomarker for GBM. We utilized the GBM-TCGA dataset and presented the reproducible bioinformatics analysis for our results. We identified that GPRC5A expression was significantly upregulated in GBM compared to normal tissues, with higher levels correlating with poor overall survival (OS) and progression-free interval (PFI). Moreover, it was associated with key genetic mutations, particularly NF1 and PTEN mutations, and strongly correlated with the mesenchymal stem-like phenotype. GPRC5A was also predominantly associated with aggressive GBM features, including hypoxia, high extracellular matrix (ECM) environments, and extensive stromal and immune infiltrations. Its strong correlation with mesenchymal markers and hypoxic regions underscores its potential as a biomarker and therapeutic target in GBM. These findings provide valuable insights into the role of GPRC5A in GBM pathology and its potential impact as a target for GBM stratifications and treatment strategies.

Abstract Background Despite the prevalence of distance learning during COVID-19, conducting clinical training for nursing students remains challenging. In compliance with social-distancing restrictions, a Zoom-based virtual OSCE preparation program for nursing students was designed, and it included clinical skills. The aims of this study were to assess nursing students’ satisfaction with a virtual program for Objective Structured Clinical Examination (OSCE) preparation, and to evaluate its learning outcomes measured by OSCE scores as compared to those of in-person preparation programs. Methods A descriptive and repeated cross-sectional study was designed. Students’ satisfaction with the virtual program was based on a post-course survey and personal reflections. OSCE scores of graduates of the virtual program (n = 82) tested in 2021 were compared to those of 337 graduates of in-person programs tested in 2017–2020. Results A post-program survey revealed that 88% of the students in 2021 were satisfied with the virtual program and felt it prepared them properly for the OSCE (26% agree and 62% strongly agree). No significant differences were found between OSCE scores following the virtual program conducted in 2021 and scores following in-person programs conducted in 2017–2020. Conclusions This study suggests that nursing education can benefit from integrating virtual programs which incorporate clinical practices into the curricula, without harming student competency. The study results may address the problem of maintaining clinical practices in a time of limited accessibility, and in settings of low resources. It is important to expand the investigation to long-term impact of virtual training programs on nursing students’ competencies.

Abstract Background Evidence has shown that restrictions during the COVID-19 pandemic have negatively affected breastfeeding support and outcomes in hospitals in many countries. The aims of the study were to describe exclusive breastfeeding rates and identify factors associated with exclusive breastfeeding at hospital discharge among women who gave birth during the COVID-19 pandemic in Israel. Methods A cross-sectional online anonymous survey based on WHO standards for improving quality of maternal and newborn care in health facilities was conducted among a sample of women who gave birth to a healthy singleton infant in Israel during the pandemic (between March 2020 and April 2022). The socio-ecological approach was employed to examine intrapersonal, interpersonal, organizational, and community/society factors associated with exclusive breastfeeding at hospital discharge according to women perspectives. Results Among the 235 Israeli participants, 68.1% exclusively breastfed, 27.7% partially breastfed, and 4.2% did not breastfeed at discharge. Results of the adjusted logistic regression model showed that factors significantly associated with exclusive breastfeeding were the intrapersonal factor of multiparity (adjusted OR 2.09; 95% Confidence Interval 1.01,4.35) and the organizational factors of early breastfeeding in the first hour (aOR 2.17; 95% CI 1.06,4.45), and rooming-in (aOR 2.68; 95% CI 1.41,5.07). Conclusions Facilitating early breastfeeding initiation and supporting rooming-in are critical to promoting exclusive breastfeeding. These factors, reflecting hospital policies and practices, along with parity, are significantly associated with breastfeeding outcomes and highlight the influential role of the maternity environment during the COVID-19 pandemic. Maternity care in hospitals should follow evidence-based breastfeeding recommendations also during the pandemic, promoting early exclusive breastfeeding and rooming-in among all women, with particular attention to providing lactation support to primiparous women. Trial registration Clinical Trials NCT04847336.

Given advancements in large-scale data and AI, integrating multimodal artificial intelligence into cancer research can enhance our understanding of tumor behavior by simultaneously processing diverse biomedical data types. In this review, we explore the potential of multimodal AI in comprehending B-cell non-Hodgkin lymphomas (B-NHLs). B-cell non-Hodgkin lymphomas (B-NHLs) represent a particular challenge in oncology due to tumor heterogeneity and the intricate ecosystem in which tumors develop. These complexities complicate diagnosis, prognosis, and therapy response, emphasizing the need to use sophisticated approaches to enhance personalized treatment strategies for better patient outcomes. Therefore, multimodal AI can be leveraged to synthesize critical information from available biomedical data such as clinical record, imaging, pathology and omics data, to picture the whole tumor. In this review, we first define various types of modalities, multimodal AI frameworks, and several applications in precision medicine. Then, we provide several examples of its usage in B-NHLs, for analyzing the complexity of the ecosystem, identifying immune biomarkers, optimizing therapy strategy, and its clinical applications. Lastly, we address the limitations and future directions of multimodal AI, highlighting the need to overcome these challenges for better clinical practice and application in healthcare.

Abstract Background Exclusive breastfeeding is the optimal infant nutrition, providing infants immunoprotection against many diseases including SARS-CoV-2 infection. Restrictions during the COVID-19 pandemic may have negatively affected breastfeeding practices in maternity care facilities. The aims of the study were to examine exclusive breastfeeding rates at discharge over time and to identify factors associated with exclusive breastfeeding during the pandemic. Methods A cross-sectional survey was conducted among mothers who gave birth in a maternity care facility in the World Health Organization (WHO) European Region countries during the COVID-19 pandemic. The socio-ecological model was employed to examine intrapersonal, interpersonal, organizational, and community/society factors associated with maternal report of exclusive breastfeeding at the time of discharge. Results There were 26,709 participating mothers from 17 European Region countries who were included in the analysis. Among the mothers, 72.4% (n = 19,350) exclusively breastfed and 27.6% (n = 7,359) did not exclusively breastfeed at discharge. There was an overall decline in exclusive breastfeeding rates over time (p = 0.015) with a significantly lower rate following the publication of the WHO breastfeeding guidelines on 23 June 2020 (AOR 0.88; 95% CI 0.82, 0.94). Factors significantly associated with exclusive breastfeeding outcomes in the logistic regression analysis included maternal age, parity, education, health insurance, mode of birth, inadequate breastfeeding support, lack of early breastfeeding initiation, lack of full rooming-in, birth attendant, perceived healthcare professionalism and attention, facility room cleanliness, timing of birth, and location of birth. Conclusions Results from the study indicate the decline in exclusive breastfeeding rates in the WHO European Region during the COVID-19 pandemic. Using the socio-ecological model to identify factors associated with breastfeeding outcomes facilitates an integrated and holistic approach to address breastfeeding needs among women across the region. These findings demonstrate the need to augment breastfeeding support and to protect exclusive breastfeeding among mother-infant dyads, in an effort to reverse the declining exclusive breastfeeding rates. The study highlights the need to educate mothers and their families about the importance of exclusive breastfeeding, reduce maternal-infant separation, increase professional breastfeeding support, and follow evidence-based practice guidelines to promote breastfeeding in a comprehensive and multi-level manner. Trial registration number Clinical Trials NCT04847336.

Abstract Background Fear of falling (FoF) is an important risk factor for falls among older people. The objectives of our investigations were: a.) to present characteristics of older community-dwelling (CD) fallers with persistent or transient FoF (P-FoF or T-FoF) over 12 months, and b.) to investigate clinical predictors of P-FoF and T-FoF and c.) to explore differences between P-FoF and T-FoF. Methods Our series consisted of 389 older people reporting a fall or injurious fall at baseline and during 24 months follow-up participating in a multicenter prospective study. T-FoF was defined as participants reported “not at all” at baseline and “somewhat/fairly/very concerned” at follow-up, or “not at all” at follow-up, and “somewhat/fairly/very concerned” at baseline, and P-FoF was defined as participants answered “somewhat/fairly/very concerned” in both assessments at baseline and at follow-up. The association between risk factors and T-FoF or P-FoF was investigated by logistic regression analysis. Results The mean age of fallers in our sample was 79.0 years (SD 6.0), and 54.2% were females. Out of 389 older adults with a fall history at baseline, 83 participants (21.3%) did not report any FoF over time, P-FoF and T-FoF were observed in 42.7% and 35.9% of participants, respectively. After adjusting for potential confounders (e.g. age, gender), osteoporosis (OR = 2.04, 95%CI = 1.03–4.05) and impaired physical performance (OR = 2.38, 95%CI = 1.12–5.03) were significant predictors of T-FoF vs No-FoF. Osteoporosis (OR = 2.68, 95%CI = 1.31–5.48), depressive symptoms (OR = 3.54, 95%CI = 1.23–10.1) and living alone (OR = 2.44, 95%CI = 1.17–5.06) were significantly associated with P-FoF vs No-FoF. When comparing T-FoF and P-FoF, female gender (OR = 1.95, 95%CI = 1.16–3.27), BMI (OR = 1.08, 95%CI = 1.02–1.14), overall comorbidity (OR = 1.07, 95%CI = 1.02–1.13) and depression (OR = 2.55, 95%CI = 1.33–4.88) were significant predictors of P-FoF. Conclusions T-FoF and P-FoF may be predicted by different sets of risk factors among older fallers. Thus, fallers should be screened for FoF especially when carrying specific risk factors, including female gender, osteoporosis, depression, living alone, impaired physical performance, BMI, comorbidity. These findings may be helpful in designing tailored intervention to blunt the risks related to consequence of FoF among older people experiencing falls. Trial registration The SCOPE study was registered prospectively at clinicaltrials.gov (NCT02691546; 25/02/2016).

Abstract Background Sarcopenia may be more present in older adults with diabetes (DM). Accordingly, we evaluated the prevalence of sarcopenia and its associated risk factors among community-dwelling older adults with DM. Methods A cross-sectional analysis of older people living in the community was carried out. Participants (aged 75 years and more) came from an European multicenter prospective cohort (SCOPE study). Global geriatric assessment including short physical performance battery, handgrip strength test and bioelectrical impedance analysis was performed. Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate (eGFR) was calculated using Berlin Initiative Study (BIS) to define the stages of chronic kidney disease (CKD). Previous known DM was defined as physician-diagnosed DM registered in the patient's medical record or the use of DM-related medications. Hemoglobin A1c levels and specific DM therapies administered were collected. Time elapsed from the first diagnosis of DM was not collected and, therefore, was not included in the analyses. Results A total of 1,420 subjects were evaluated with a median age of 79.0 (6.0) years, of which 804 (56.6%) were women and 615 (43.3%) men; 315 (22.2%) participants had prior DM diagnosis, with a median age of 80.0 (6.0), 146 (46.3%) were women. Using EWGSOP2 definition, 150 (10.6%) participants in the SCOPE study met diagnostic criteria for sarcopenia. Participants without diabetes had more often normal results in the 3 sarcopenia components than participants with diabetes [887 (80.31%) vs. 227 (72.1%), p = 0.002], highlighting higher percentages of severe sarcopenia in participants with diabetes [27 (8.6%) vs. 58 (5.2%), p = 0.028]. Confirmed or severe sarcopenia was detected in 41 (13%) participants with diabetes and 109 (9.8%) participants without diabetes (p = 0.108). According to BIS equation, sarcopenia was not significantly more prevalent in the more advanced stages of CKD (p = 0.845). In multivariate analyses, older age (odds ratios [OR], 1.17; 95% confidence interval [CI], 1.08–1.27), and lower body mass index (OR, 0.79; 95% CI, 0.71–0.89 were associated with the presence of sarcopenia. Conclusions One tenth of all older community-dwelling subjects have sarcopenia. Older age and being thinner, but not worse renal function, were associated with higher prevalence of sarcopenia in older older adults with diabetes.

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique ability to mediate inflammatory responses of the immune system. Given the critical role of DCs in shaping immunity, they present an attractive avenue as a therapeutic target to program the immune system and reverse immune disease disorders. To ensure appropriate immune response, DCs utilize intricate and complex molecular and cellular interactions that converge into a seamless phenotype. Computational models open novel frontiers in research by integrating large-scale interaction to interrogate the influence of complex biological behavior across scales. The ability to model large biological networks will likely pave the way to understanding any complex system in more approachable ways. We developed a logical and predictive model of DC function that integrates the heterogeneity of DCs population, APC function, and cell-cell interaction, spanning molecular to population levels. Our logical model consists of 281 components that connect environmental stimuli with various layers of the cell compartments, including the plasma membrane, cytoplasm, and nucleus to represent the dynamic processes within and outside the DC, such as signaling pathways and cell-cell interactions. We also provided three sample use cases to apply the model in the context of studying cell dynamics and disease environments. First, we characterized the DC response to Sars-CoV-2 and influenza co-infection by in-silico experiments and analyzed the activity level of 107 molecules that play a role in this co-infection. The second example presents simulations to predict the crosstalk between DCs and T cells in a cancer microenvironment. Finally, for the third example, we used the Kyoto Encyclopedia of Genes and Genomes enrichment analysis against the model’s components to identify 45 diseases and 24 molecular pathways that the DC model can address. This study presents a resource to decode the complex dynamics underlying DC-derived APC communication and provides a platform for researchers to perform in-silico experiments on human DC for vaccine design, drug discovery, and immunotherapies.

Abstract Follicular lymphoma (FL) is a B-cell non-Hodgkin lymphoma of germinal center (GC) origin with a distinctive tumor microenvironment (TME) and a unique spectrum of mutations. Despite the important therapeutic advances, FL is still incurable. During B-cell development, the GC reaction is a complex multistep process in which epigenetic regulators dynamically induce or suppress transcriptional programs. In FL, epigenetic gene mutations perturb the regulation of these programs, changing GC B-cell function and skewing differentiation towards tumor cells and altering the microenvironment interactions. FL pathogenesis and malignant transformation are promoted by epigenetic reprogramming of GC B cells that alters the immunological synapse and niche. Despite the extensive characterization of FL epigenetic signature and TME, the functional consequences of epigenetic dysregulation on TME and niche plasticity need to be better characterized. In this review, first we describe the most frequent epigenomic alterations in FL (KMT2D, CREBBP and EZH2) that affect the immunological niche, and their potential consequences on the informational transfer between tumor B cells and their microenvironment. Then, we discuss the latest progress to harness epigenetic targets for inhibiting the FL microenvironment. Finally, we highlight unexplored research areas and outstanding questions that should be considered for a successful long-term treatment of FL.

Background: This study examined students' perceptions of and engagement with active student responding (ASR) techniques as they relate to student performance. Objective: We replicate Zayac et al.'s study on ASR methods and expand on it by using an upper-level psychology course at multiple institutions and additional measures of engagement. Method: The current study used a within-subjects, counter-balanced design, with data collected from 103 students at four universities. Results: Though no differences in exam scores across ASR conditions were observed, there were differences in student perceptions and engagement. ASR techniques providing increased anonymity resulted in greater student perceptions and engagement than control conditions. Additionally, extraverted students reported greater cognitive and emotional engagement with nonanonymous ASR techniques. Conclusion: Findings support some positive impacts of ASR techniques, especially for those that allow for increased student anonymity. Implications for Teaching: Instructors should be selective and critical about adopting ASR techniques in the classroom, as anonymous ones may allow for increased student engagement and accommodations for some but have the potential for distraction or disengagement for others.

Abstract CD4+ T cells provide adaptive immunity against pathogens and abnormal cells, and they are also associated with various immune-related diseases. CD4+ T cells’ metabolism is dysregulated in these pathologies and represents an opportunity for drug discovery and development. Genome-scale metabolic modeling offers an opportunity to accelerate drug discovery by providing high-quality information about possible target space in the context of a modeled disease. Here, we develop genome-scale models of naïve, Th1, Th2, and Th17 CD4+ T-cell subtypes to map metabolic perturbations in rheumatoid arthritis, multiple sclerosis, and primary biliary cholangitis. We subjected these models to in silico simulations for drug response analysis of existing FDA-approved drugs and compounds. Integration of disease-specific differentially expressed genes with altered reactions in response to metabolic perturbations identified 68 drug targets for the three autoimmune diseases. In vitro experimental validation, together with literature-based evidence, showed that modulation of fifty percent of identified drug targets suppressed CD4+ T cells, further increasing their potential impact as therapeutic interventions. Our approach can be generalized in the context of other diseases, and the metabolic models can be further used to dissect CD4+ T-cell metabolism.

Abstract Background Chronic kidney disease (CKD), cognitive impairment and depression share common risk factors. Previous studies did not investigate the possible association between kidney function and cognitive and mood disorders in older persons in a broad range of kidney function. The present study explored associations between kidney function, cognition and mood in outpatients of 75 years and over. Methods Baseline data of 2252 participants of the SCOPE study, an international multicenter cohort observational study,were used in which community-dwelling persons of 75 years and over were enrolled to screen for CKD Kidney function was estimated with the BIS1-eGFR equation, cognition was assessed with the Mini-Mental State Examination (MMSE) and mood with the Geriatric Depression Scale 15 items (GDS-15). Characteristics were compared across stages of CKD. Mean eGFR values were also compared across categories of MMSE ( 5/≤5). Results In total, 63% of the population had an eGFR

Abstract Background Different mechanisms connect the nutritional status with the occurrence and the course of chronic kidney disease (CKD). The end-stage renal disease is complicated by catabolic inflammatory reactions and cachexia which leads to malnutrition (undernutrition). On the other hand, obesity is an important risk factor for the development and acceleration of CKD. Methods In the SCOPE study, community-dwelling persons aged 75 years and over, from 6 European countries and Israel were examined at the baseline phase. We assessed the relationship between anthropometric measures (Body Mass Index (BMI), circumferences of arm (AC), waist (WC), hip (HC), and calf (CC), waist-to-hip ratio - WHR, waist-to-height ratio - WHtR, risk of malnutrition (Mini Nutritional Assessment - MNA), serum albumin) and estimated glomerular filtration rate (eGFR) calculated by Berlin Initiative Study (BIS) equation. Results We studied 2151 subjects (932 men and 1219 women) with a mean age of 79.5 ± 5.9 years. A total of 1333 (62%) participants had CKD (GRF 60 (OR = 2.95, 95%CI = 1.77–4.94 for MNA

Abstract Background Reduced kidney function has become a major public health concern, especially among older people, as Chronic Kidney Disease (CKD) is associated with increased risk of end stage renal disease and mortality. Falls are a serious negative health outcome in older persons with one third of people aged 65 years experiencing a fall per year and increasing fall rates with increasing age. The impact of CKD on falls in older community-dwelling persons is not well investigated. Additionally, lower urinary tract symptoms (LUTS) may also increase the risk of falls. Therefore, our aim was to investigate the impact of CKD and LUTS on falls as well as on injurious falls. Methods The SCOPE study is an observational, multinational, multicenter, prospective cohort study involving community-dwelling older persons aged 75 years and more recruited from August 2016 to March 2018 in seven European countries. The main outcomes of the present study were any falls and any injurious falls during the 12 months before enrolment. The cross-sectional association of estimated glomerular filtration rate (eGFR) and LUTS with study outcomes was investigated by logistic regression analysis adjusted for baseline characteristics of enrolled subjects. Results Our series consisted of 2256 SCOPE participants (median age = 79.5 years, 55.7% female). Of them, 746 participants experienced a fall and 484 reported an injurious fall in the 12 months prior to baseline assessment. CKD was not significantly associated with falls (OR = 0.95, 95%CI = 0.79–1.14 for eGFR

Abstract Background Quality of life (QoL) refers to the physical, psychological, social and medical aspects of life that are influenced by health status and function. The purpose of this study was to measure the self-perceived health status among the elderly population across Europe in different stages of Chronic Kidney Disease (CKD). Methods Our series consisted of 2255 community-dwelling older adults enrolled in the Screening for Chronic Kidney Disease (CKD) among Older People across Europe (SCOPE) study. All patients underwent a comprehensive geriatric assessment (CGA), including included demographics, clinical and physical assessment, number of medications taken, family arrangement, Geriatric Depression Scale (GDS), Cumulative Illness Rating Scale, History of falls, Lower urinary tract symptoms, and Short Physical Performance Battery (SPPB). Estimated glomerular filtration rate (eGFR) was calculated by Berlin Initiative Study (BIS) equation. Quality of life was assessed by Euro Qol questionnaire (Euro-Qol 5D) and EQ-Visual Analogue Scale (EQ-VAS). The association between CKD (eGFR

Perjanjian pinjam nama atau biasanya dikenal dengan istilah perjanjian nominee merupakan salah satu upaya dari warga asing agar bisa memperoleh hak kepemilikan tanah di Negara Kesatuan Republik Indonesia melalui cara meminjam nama warga Negara Indonesia, kemudian dimasukkan pada sertifikat kepemilikan yang mana seluruh pembiayaan ditanggung oleh pihak warga negara asing. Peraktik pinjam nama ini bukan suatu hal yang asing lagi oleh masyarakat Indonesia dan merupakan bentuk penyelundupan hukum tanah, mengingat adanya ketentuan Undang-Undang Nomor 5 Tahun 1960 Tentang Peraturan Dasar Pokok-Pokok Agraria pada Pasal 21 Ayat (1) yang menyebutkan “Hanya Warga Negara Indonesia yang mempunyai hak milik”. Tujuan penelitian agar dapat memahami apakah Perjanjian nominee selaras dengan hukum positif Indonesia dan bagaimana penerapan asas kebangsaan dalam perjanjian nominee. Metode yang dipakai oleh penelitian ini adalah metode penelitian normative yang lebih menitikberatkan pada pendekatan Perundang-undangan dan konseptual. Kesimpulan dari penelitian ini bahwa perjanjian nominee tidak selaras oleh peraturan yang berlaku di Negara Kesatuan Republik Indonesia disebabkan melanggar persyaratan suatu perjanjian berupa causa yang halal dan melanggar asas perjanjian yaitu asas kebebasan berkontrak dan berakibat batal demi hukum. Kemudian, penerapan asas kebangsaan dalam perjanjian nominee tidak tepat dan sangat bertentangan disebabkan tidak memenuhi syarat yang tertuang dalam Pasal 9 Ayat (1) dan (2).

T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) negatively regulates innate and adaptive immunity in cancer. To identify the mechanisms of Tim-3 in cancer immunity, we evaluated the effects of Tim-3 blockade in human and mouse melanoma. Here, we show that human programmed cell death 1–positive (PD-1+) Tim-3+CD8+ tumor-infiltrating lymphocytes (TILs) upregulate phosphatidylserine (PS), a receptor for Tim-3, and acquire cell surface myeloid markers from antigen-presenting cells (APCs) through transfer of membrane fragments called trogocytosis. Tim-3 blockade acted on Tim-3+ APCs in a PS-dependent fashion to disrupt the trogocytosis of activated tumor antigen–specific CD8+ T cells and PD-1+Tim-3+ CD8+ TILs isolated from patients with melanoma. Tim-3 and PD-1 blockades cooperated to disrupt trogocytosis of CD8+ TILs in 2 melanoma mouse models, decreasing tumor burden and prolonging survival. Deleting Tim-3 in dendritic cells but not in CD8+ T cells impeded the trogocytosis of CD8+ TILs in vivo. Trogocytosed CD8+ T cells presented tumor peptide–major histocompatibility complexes and became the target of fratricide T cell killing, which was reversed by Tim-3 blockade. Our findings have uncovered a mechanism Tim-3 uses to limit antitumor immunity.

Objectives Develop and validate a WHO Standards-based online questionnaire to measure the quality of maternal and newborn care (QMNC) around the time of childbirth from the health workers’ perspective.Design Mixed-methods study.Setting Six countries of the WHO European Region.Participants and methods The questionnaire is based on lessons learnt in previous studies, and was developed in three sequential phases: (1) WHO Quality Measures were prioritised and content, construct and face validity were assessed through a Delphi involving a multidisciplinary board of experts from 11 countries of the WHO European Region; (2) translation/back translation of the English version was conducted following The Professional Society for Health Economics and Outcomes Research guidelines; (3) internal consistency, intrarater reliability and acceptability were assessed among 600 health workers in six countries.Results The questionnaire included 40 items based on WHO Standards Quality Measures, equally divided into four domains: provision of care, experience of care, availability of human and physical resources, organisational changes due to COVID-19; and its organised in six sections. It was translated/back translated in 12 languages: Bosnian, Croatian, French, German, Italian, Norwegian, Portuguese, Romanian, Russian, Slovenian, Spanish and Swedish. The Cronbach’s alpha values were ≥0.70 for each questionnaire section where questions were hypothesised to be interrelated, indicating good internal consistence. Cohen K or Gwet’s AC1 values were ≥0.60, suggesting good intrarater reliability, except for one question. Acceptability was good with only 1.70% of health workers requesting minimal changes in question wording.Conclusions Findings suggest that the questionnaire has good content, construct, face validity, internal consistency, intrarater reliability and acceptability in six countries of the WHO European Region. Future studies may further explore the questionnaire’s use in other countries, and how to translate evidence generated by this tool into policies to improve the QMNC.Trail registration number NCT04847336