JBP1 and JBP3 have conserved structures but different affinity to base-J.

Base-J (β-D-glucopyranosyloxymethyluracil) is an unusual kinetoplastid-specific DNA modification, recognized by base-J containing DNA (J-DNA) binding proteins JBP1 and JBP3. Recognition of J-DNA by both JBP1 and JBP3 takes place by a conserved J-DNA binding domain (JDBD). Here we show that JDBD-JBP3 has about 1,000-fold weaker affinity to base-J than JDBD-JBP1 and discriminates between J-DNA and unmodified DNA with a factor ∼5, whereas JDBD-JBP1 discriminates with a factor ∼10,000.

Early-twentieth-century cold bias in ocean surface temperature observations.

The observed temperature record, which combines sea surface temperatures with near-surface air temperatures over land, is crucial for understanding climate variability and change. However, early records of global mean surface temperature are uncertain owing to changes in measurement technology and practice, partial documentation, and incomplete spatial coverage. Here we show that existing estimates of ocean temperatures in the early twentieth century (1900-1930) are too cold, based on independent statistical reconstructions of the global mean surface temperature from either ocean or land data.

Correction: Chisholm et al. Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) Clinical Trial: A Report from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG). 2024, , 998.

The authors wish to make corrections to the authorship and title of [...

The Next Era of Assessment Within Medical Education: Exploring Intersections of Context and Implementation.

In competency-based medical education (CBME), which is being embraced globally, the patient-learner-educator encounter occurs in a highly complex context which contributes to a wide range of assessment outcomes. Current and historical barriers to considering context in assessment include the existing post-positivist epistemological stance that values objectivity and validity evidence over the variability introduced by context. This is most evident in standardized testing.

Targeted nanomedicine for reprogramming the tumor innate immune system: From bench to bedside.

Tumor-associated innate immune cells such as tumor-associated macrophages, neutrophils, dendritic cells play a crucial role in tumor progression, angiogenesis and metastasis. These cells also control the efficacy of chemotherapy and immunotherapy by inducing drug resistance and immunosuppression, leading to therapeutic failures. Therefore, targeting the tumor-associated innate immune cells has gained high attention for the development of effective cancer therapy.

Design of TOLERANT: phase I/II safety assessment of intranodal administration of HSP70/mB29a self-peptide antigen-loaded autologous tolerogenic dendritic cells in patients with rheumatoid arthritis.

Introduction: In rheumatoid arthritis (RA), immunosuppressive therapies may achieve symptomatic relief, but do not induce long-term, drug-free remission. Meanwhile, the lifelong use of immunosuppressive drugs confers increased risk for malignancy and infections. As such, there is an unmet need for novel treatments that selectively target the pathogenic immune response in RA by inducing tolerance to autoantigens.

Increasing extreme precipitation variability plays a key role in future record-shattering event probability.

Climate events that break records by large margins are a threat to society and ecosystems. Climate change is expected to increase the probability of such events, but quantifying these probabilities is challenging due to natural variability and limited data availability, especially for observations and very rare extremes. Here we estimate the probability of precipitation events that shatter records by a margin of at least one pre-industrial standard deviation.

Unsupervised denoising of the non-invasive fetal electrocardiogram with sparse domain Kalman filtering and vectorcardiographic loop alignment.

Even though the electrocardiogram (ECG) has potential to be used as a monitoring or diagnostic tool for fetuses, the use of non-invasive fetal ECG is complicated by relatively high amounts of noise and fetal movement during the measurement. Moreover, machine learning-based solutions to this problem struggle with the lack of clean reference data, which is difficult to obtain. To solve these problems, this work aims to incorporate fetal rotation correction with ECG denoising into a single unsupervised end-to-end trainable method.

Exploring immune status in peripheral blood and tumor tissue in association with survival in patients with multi-organ metastatic colorectal cancer.

Colorectal cancer (CRC) raises considerable clinical challenges, including a high mortality rate once the tumor spreads to distant sites. At this advanced stage, more accurate prediction of prognosis and treatment outcome is urgently needed. The role of cancer immunity in metastatic CRC (mCRC) is poorly understood.

Evaluating the Quality of Narrative Feedback for Entrustable Professional Activities in a Surgery Residency Program.

Objective: To assess the quality of narrative feedback given to surgical residents during the first 5 years of competency-based medical education implementation.

Background: Competency-based medical education requires ongoing formative assessments and feedback on learners' performance.

Methods: We conducted a retrospective cross-sectional study using assessments of entrustable professional activities (EPAs) in the Surgical Foundations curriculum at Queen's University from 2017 to 2022.

Examining Individual and Contextual Correlates of Victimization for Juvenile Human Trafficking in Florida.

Despite extant literature on individual-level risk factors for sex trafficking among children and adolescents, little is known about the impact of social and ecological contexts on risk of human trafficking victimization. The purpose of this study was to examine the correlates signaling risk of human trafficking victimization at the individual, family, social, and community levels utilizing a sample of 40,531 justice-involved male and female youth, a small fraction of whom were suspected or verified victims of human trafficking between 2011 and 2015 ( = 801, including 699 female and 102 male youth). Using this sample, we examined differences across individual, family, social, and community characteristics of youth involved in the juvenile justice system who have a history of trafficking victimization and youth without such histories.

Fully closed and automated enrichment of primary blood dendritic cells for cancer immunotherapy.

Dendritic cell (DC) vaccination is a promising approach to induce tumor-specific immune responses in cancer patients. Until recently, most DC vaccines were based on in vitro-differentiated monocyte-derived DCs. However, through development of efficient isolation techniques, the use of primary blood dendritic cell subsets has come within reach.

cDC2 plasticity and acquisition of a DC3-like phenotype mediated by IL-6 and PGE2 in a patient-derived colorectal cancer organoids model.

Metastatic colorectal cancer (CRC) is highly resistant to therapy and prone to recur. The tumor-induced local and systemic immunosuppression allows cancer cells to evade immunosurveillance, facilitating their proliferation and dissemination. Dendritic cells (DCs) are required for the detection, processing, and presentation of tumor antigens, and subsequently for the activation of antigen-specific T cells to orchestrate an effective antitumor response.

Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) Clinical Trial: A Report from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG).

The Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) clinical trial is an overarching, multinational study for children and adults with rhabdomyosarcoma (RMS). The trial, developed by the European Soft Tissue Sarcoma Study Group (EpSSG), incorporates multiple different research questions within a multistage design with a focus on (i) novel regimens for poor prognostic subgroups, (ii) optimal duration of maintenance chemotherapy, and (iii) optimal use of radiotherapy for local control and widespread metastatic disease. Additional sub-studies focusing on biological risk stratification, use of imaging modalities, including [F]FDG PET-CT and diffusion-weighted MRI imaging (DWI) as prognostic markers, and impact of therapy on quality of life are described.

Dendritic cell vaccination combined with carboplatin/paclitaxel for metastatic endometrial cancer patients: results of a phase I/II trial.

Background: Metastatic endometrial cancer (mEC) continues to have a poor prognosis despite the introduction of several novel therapies including immune checkpoints inhibitors. Dendritic cell (DC) vaccination is known to be a safe immunotherapeutic modality that can induce immunological and clinical responses in patients with solid tumors. Platinum-based chemotherapy is known to act synergistically with immunotherapy by selectively depleting suppressive immune cells.

Adjuvant dendritic cell therapy in stage IIIB/C melanoma: the MIND-DC randomized phase III trial.

Autologous natural dendritic cells (nDCs) treatment can induce tumor-specific immune responses and clinical responses in cancer patients. In this phase III clinical trial (NCT02993315), 148 patients with resected stage IIIB/C melanoma were randomized to adjuvant treatment with nDCs (n = 99) or placebo (n = 49). Active treatment consisted of intranodally injected autologous CD1c+ conventional and plasmacytoid DCs loaded with tumor antigens.

Deep Learing for Sparse Domain Kalman Filtering With Applications on ECG Denoising and Motility Estimation.

Objective: The reconstruction of an input based on a sparse combination of signals, known as sparse coding, has found widespread use in signal processing. In this work, the combination of sparse coding with Kalman filtering is explored and its potential is shown on two use-cases.

Methods: This work extends the Iterative Shrinkage and Thresholding Algorithm with a Kalman filter in the sparse domain.

Targeted Sequencing of Circular RNAs for Illumina-Based Counting and Nanopore Structure Determination.

In the past years, circular RNAs (circRNAs) became a major focus of many studies in animals and plants. circRNAs are generated by backsplicing from the same linear transcripts that are canonically spliced to produce, for example, mature mRNAs. They exhibit tissue-specific expression pattern and are potentially involved in many diseases, among them cardiovascular diseases.

Professional societies of obstetrics and gynecology as agents of change in sexual and reproductive health: FIGO's 10-country safe abortion advocacy project in Africa and Latin America.

In 2019, FIGO started implementing its abortion project focusing on advocacy. The Advocacy for Safe Abortion (ASA) Project was conducted in partnership with 10 national professional societies of obstetrics and gynecology in Latin America and Africa. The project aimed to strengthen national societies, support them to be leaders in sexual and reproductive health, and enable them to obtain context-specific advocacy goals that improve access to safe abortion.

The role of healthcare providers in expanding legal abortion: Qualitative insights from Argentina, Ireland, and South Korea.

Abortion laws are key in creating an enabling environment that facilitates the advancement of people's sexual and reproductive health and rights. Around 50 countries have liberalized their abortion laws in the last decades by adding new grounds allowing abortion. The road toward the expansion of legal abortion is a long, highly sensitive, and difficult process.