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Abstract Background and Objective Acute myelogenous leukemia (AML) is a common blood cancer marked by heterogeneity in disease and diverse genetic abnormalities. Additional therapies are needed as the 5-year survival remains below 30%. Trametinib is a mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor that is widely used in solid tumors and also in tumors with activating RAS mutations. A subset of patients with AML carry activating RAS mutations; however, a small-scale clinical trial with trametinib showed little efficacy. Here, we sought to identify transcriptomic determinants of trametinib sensitivity in AML. Methods We tested the activity of trametinib against a panel of tumor cells from patients with AML ex vivo and compared this with RNA sequencing (RNA-Seq) data from untreated blasts from the same patient samples. We then used a correlation analysis between gene expression and trametinib sensitivity to identify potential biomarkers predictive of drug response. Results We found that a subset of AML tumor cells were sensitive to trametinib ex vivo, only a fraction of which (3/10) carried RAS mutations. On the basis of our RNA-Seq analysis we found that markers of trametinib sensitivity are associated with a myeloid differentiation profile that includes high expression of CD14 and CLEC7A (Dectin-1), similar to the gene expression profile of monocytes. Further characterization confirmed that trametinib-sensitive samples display features of monocytic differentiation with high CD14 surface expression and were enriched for the M4 subtypes of the FAB classification. Conclusions Our study identifies additional molecular markers that can be used with molecular features including RAS status to identify patients with AML that may benefit from trametinib treatment.

Continuous probabilistic genotyping (PG) provides a means to estimate the probative value of DNA mixtures tendered as evidence in court and subject to alternative propositions about the contributors to the mixtures. The weight of that evidence, however, may be valued differently, depending on which forensic laboratory undertook the DNA analysis. There is a need, therefore, to have a means for the comparison of likelihood ratios (LRs) generated by continuous PG amongst different laboratories for the same initial DNA sample. Such a comparison would enable the courts and the public to make judgements about the reliability of this type of evidence. There are particular mixtures and methods for which such a comparison is meaningful, and this study explores them for the short tandem repeat (STR) electropherograms of two-person mixtures obtained from the PROVEDIt Database. We demonstrate a common maximum attainable LR for a given set of common STR loci and a given DNA mixture that is consistent across three different STR profiling assays and two different capillary electrophoresis instruments.

BackgroundEmpathy, a fundamental aspect of human interaction, is characterized as the ability to experience another being’s emotions within oneself. In health care, empathy is a fundamental for health care professionals and patients’ interaction. It is a unique quality to humans that large language models (LLMs) are believed to lack. ObjectiveWe aimed to review the literature on the capacity of LLMs in demonstrating empathy. MethodsWe conducted a literature search on MEDLINE, Google Scholar, PsyArXiv, medRxiv, and arXiv between December 2022 and February 2024. We included English-language full-length publications that evaluated empathy in LLMs’ outputs. We excluded papers evaluating other topics related to emotional intelligence that were not specifically empathy. The included studies’ results, including the LLMs used, performance in empathy tasks, and limitations of the models, along with studies’ metadata were summarized. ResultsA total of 12 studies published in 2023 met the inclusion criteria. ChatGPT-3.5 (OpenAI) was evaluated in all studies, with 6 studies comparing it with other LLMs such GPT-4, LLaMA (Meta), and fine-tuned chatbots. Seven studies focused on empathy within a medical context. The studies reported LLMs to exhibit elements of empathy, including emotions recognition and emotional support in diverse contexts. Evaluation metric included automatic metrics such as Recall-Oriented Understudy for Gisting Evaluation and Bilingual Evaluation Understudy, and human subjective evaluation. Some studies compared performance on empathy with humans, while others compared between different models. In some cases, LLMs were observed to outperform humans in empathy-related tasks. For example, ChatGPT-3.5 was evaluated for its responses to patients’ questions from social media, where ChatGPT’s responses were preferred over those of humans in 78.6% of cases. Other studies used subjective readers’ assigned scores. One study reported a mean empathy score of 1.84-1.9 (scale 0-2) for their fine-tuned LLM, while a different study evaluating ChatGPT-based chatbots reported a mean human rating of 3.43 out of 4 for empathetic responses. Other evaluations were based on the level of the emotional awareness scale, which was reported to be higher for ChatGPT-3.5 than for humans. Another study evaluated ChatGPT and GPT-4 on soft-skills questions in the United States Medical Licensing Examination, where GPT-4 answered 90% of questions correctly. Limitations were noted, including repetitive use of empathic phrases, difficulty following initial instructions, overly lengthy responses, sensitivity to prompts, and overall subjective evaluation metrics influenced by the evaluator’s background. ConclusionsLLMs exhibit elements of cognitive empathy, recognizing emotions and providing emotionally supportive responses in various contexts. Since social skills are an integral part of intelligence, these advancements bring LLMs closer to human-like interactions and expand their potential use in applications requiring emotional intelligence. However, there remains room for improvement in both the performance of these models and the evaluation strategies used for assessing soft skills.

Previously, we showed that the germ cell-specific nuclear protein RBMXL2 represses cryptic splicing patterns during meiosis and is required for male fertility (Ehrmann et al., 2019). Here, we show that in somatic cells the similar yet ubiquitously expressed RBMX protein has similar functions. RBMX regulates a distinct class of exons that exceed the median human exon size. RBMX protein-RNA interactions are enriched within ultra-long exons, particularly within genes involved in genome stability, and repress the selection of cryptic splice sites that would compromise gene function. The RBMX gene is silenced during male meiosis due to sex chromosome inactivation. To test whether RBMXL2 might replace the function of RBMX during meiosis we induced expression of RBMXL2 and the more distantly related RBMY protein in somatic cells, finding each could rescue aberrant patterns of RNA processing caused by RBMX depletion. The C-terminal disordered domain of RBMXL2 is sufficient to rescue proper splicing control after RBMX depletion. Our data indicate that RBMX and RBMXL2 have parallel roles in somatic tissues and the germline that must have been conserved for at least 200 million years of mammalian evolution. We propose RBMX family proteins are particularly important for the splicing inclusion of some ultra-long exons with increased intrinsic susceptibility to cryptic splice site selection.

Based on the results of focus groups with students of four Russian universities, the authors describe the psycho-emotional state and social position of the student youth, the range of problems that concern them, plans for the future, priority strategies for interaction with peers and the attitude towards such ideological traits as free-thinking and originality of thinking, tolerance to the uniqueness of others and following one’s own views, motivation and determination. The study showed that under the influence of the current media agenda (primarily on the Internet), emotions of anxiety, defenselessness and uncertainty dominate among students, while the traditional media are virtually of no interest for the focus group participants, and most informants do not watch TV, including for ideological reasons. The psychological state of young people is largely determined by the media content, which they do not trust and repeatedly double-check. For students graduating from university and having a large amount of academic work, the main source of anxiety is fear of an unknown future, uncertainty in choosing a career and life goals, including in the current geopolitical situation. Russian students consider the unique features of their generation to be internal freedom and open-mindedness, constant self-development and the desire for self-realization, a combination of individualism and empathy, and constant involvement in communication with friends through social media. Among the negative traits of the youth, informants named some immaturity and unwillingness to make responsible decisions. Among the most disturbing and painful social problems in the Russian society for the youth, students emphasized social inequality caused by differences in property and income, while they calmly perceive the diversity of opinions and life strategies.

Abstract Introduction Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor used to treat tardive dyskinesia (TD) and chorea associated with Huntington disease (HD). To enhance detection of safety signals across individual trials, integrated safety analyses of deutetrabenazine in TD and HD chorea were conducted. Methods For TD, safety data were integrated from two 12-week pivotal studies (ARM-TD and AIM-TD) and through week 15 of the open-label extension (OLE) study (RIM-TD). Data were analyzed by deutetrabenazine treatment group and placebo. For HD, safety data were integrated from the 12-week pivotal study (First-HD) and through week 15 of the OLE study (ARC-HD) for patients previously receiving placebo. Integrated deutetrabenazine data were compared with placebo from the pivotal study. Results For TD, deutetrabenazine (n = 384) was generally well tolerated compared with placebo (n = 130). Adverse event (AE) incidence was numerically higher in the response-driven deutetrabenazine vs the fixed-dose deutetrabenazine and placebo groups, respectively (any AE, 59.5% vs 44.4–50.0% and 53.8%; treatment-related AE, 38.1% vs 18.1–25.0% and 30.8%). Serious AEs were reported for 2.8–8.3% of patients in the deutetrabenazine groups and 6.9% in the placebo group. Common AEs (≥ 4%) included headache, somnolence, nausea, anxiety, fatigue, dry mouth, and diarrhea. AE incidence was higher during the titration vs maintenance periods. For HD, AE incidence was numerically higher with deutetrabenazine (n = 84) vs placebo (n = 45; any AE, 64.3% vs 60.0%; treatment-related AE, 38.1% vs 26.7%); serious AEs were reported for similar proportions for the deutetrabenazine and placebo groups, 2.4% and 2.2%, respectively. Common AEs (≥ 4%) included irritability, fall, depression, dry mouth, and fatigue. Conclusions Data from an integrated analysis of studies in TD and an integrated analysis of studies of chorea in HD showed that deutetrabenazine has a favorable safety profile and is well tolerated across indications. Trial Registration ClinicalTrials.gov identifiers, NCT02291861, NCT02195700, NCT01795859, NCT02198794, NCT01897896.

This paper presents the novel task of bluespotted ribbontail (BR) ray (Taeniura lymma) recognition using deep learning based computer vision methods to enable the identification of specific individuals of this species. Mapping the specific individuals in relation to location and time will allow marine researchers to understand their movement patterns, habitat choice, life span, size of the population and more – data which could allow monitoring and establishing a tailor-made conservation plan for this species.Our work is pioneer on this recognition problem. We give a detailed description of the three basic steps of detection, feature extraction and recognition in this vision problem and perform experiments to explore the system configuration and what improves the performance. A feature extraction enhancement as well as a crucial effect of a split into different main poses are demonstrated. Though the precision results achieved in this paper are still moderate and should be further improved, they are nevertheless promising and reasonable for practical use if the six best matches are chosen. For this scenario, almost 85% precision for upper-pose model, and almost 80% precision for left- and right-pose models, are achieved demonstrating the feasibility of the pipeline suggested as well as opportunities for improvement.

Abstract Intervention by medical clowns was proven to have a positive effect in reducing stress and anxiety, increasing cooperation and improving the child's experience prior to a medical procedure and during the various stages of hospitalization. Sleep has long been known to be essential for recovery from injury and sickness, improving immune functions, and there is an emerging understanding of the restorative role quality sleep has on health and diseases. Hospitalized children are more exposed to sleep disorders and sleep deprivation due to the hospitalized environment, anxiety, and illness. Different behavioral interventions to promote sleep were previously studied in hospitalized children, some showing potential benefits. In this study, we sought to examine the ability of medical clowns to positively impact the child's sleep during hospitalization. The study is an observational matching (case–control) interventional study which took place at the department of pediatrics in Carmel Medical Center. Forty-two hospitalized children ages 2–17 were included in two equal groups of intervention or control. Children in the control group were recruited based on a method of matching the chief complaint plus the medical diagnosis and age of the children in the intervention group in a 1:1 matching. The children's sleep parameters were objectively evaluated for two consecutive nights using an Actigraph device and subjectively by parent's questionnaire. Additional factors such as hospital length of stay and demographics were also monitored. The study group had an encounter with a medical clown (15–30 min) before bedtime on either the first or the second night, and the control group was not exposed to a medical clown at all. We then compared the data from both groups using unpaired t-tests. Hospitalized children exposed to a medical clown prior to bedtime (n = 21) and children not exposed to a medical clown (n = 21) were comparable in age and clinical characteristics. The study group had a significantly delayed wake-up time compared to the control group (06:59 ± 46 min vs. 07:26 ± 42 min, p

The blackchin guitarfish Glaucostegus cemiculus has suffered severe declines and regional extirpation throughout its known distributions. While this species and its relative, the common guitarfish Rhinobatos rhinobatos, have been described in the Mediterranean Sea with co-occurring habitat ranges, no research has recorded the existence or extent of these two separate populations along the Israeli coastal waters. Along a particular coast in Israel, Ma’agan Michael, fishermen have reported annual observations of juvenile guitarfish between June to November for the last forty years. Based on these citizen-based observations the main research objective is to establish whether Ma’agan Michael fulfils all three criteria from the literature by Dr Michelle Heupel, allowing it to be acknowledged as a nursery ground for G. cemiculus. The methodology built for this objective integrates biological characteristics data with the identification of a recurrent seasonal distribution. Visual surveys exhibited a significantly higher abundance in Ma’agan Michael when compared to an adjacent area (Caesarea), with 2,096 recorded observations overall. Additionally, using a species-specific modified Catch and Release protocol, a total of 492 juveniles were captured with a beach seine net. During these capturing events, individuals were morphometrically measured and sampled for future genetic analyses. Out of these, 327 specimens were also fitted for PIT tags to track recaptures in subsequent captures. The highest abundance of neonates was caught from August to September each year (2017–2019), and all individuals captured during this study were identified in the field as G. cemiculus, ranging from 20–35 cm in length (85% of captures). Many specimens had an umbilical cord scar (n = 88), with a large percentage possessing visual remains of the yolk sac. For the first time, this study provides an inter-year description of the species Glaucostegus cemiculus present along the Israeli shoreline.

Objectives: The InVITE study, starting in August 2021, was designed to examine the immunogenicity of different vaccine regimens in several countries including the Democratic Republic of Congo, Guinea, Liberia, and Mali. Prevaccination baseline samples were used to obtain estimates of previous SARS-CoV-2 infection in the study population. Methods: Adult participants were enrolled upon receipt of their initial COVID-19 vaccine from August 2021 to June 2022. Demographic and comorbidity data were collected at the time of baseline sample collection. SARS-CoV-2 serum anti-Spike and anti-Nucleocapsid antibody levels were measured. Results: Samples tested included 1016, 375, 663, and 776, from DRC, Guinea, Liberia, and Mali, respectively. Only 0.8% of participants reported a prior positive SARS-CoV-2 test, while 83% and 68% had anti-Spike and anti-Nucleocapsid antibodies, respectively. Conclusions: Overall SARS-CoV-2 seroprevalence was 86% over the accrual period, suggesting a high prevalence of SARS-CoV-2 infection. Low rates of prior positive test results may be explained by asymptomatic infections, limited access to SARS-CoV-2 test kits and health care, and inadequate surveillance. These seroprevalence rates are from a convenience sample and may not be representative of the population in general, underscoring the need for timely, well-conducted surveillance as part of global pandemic preparedness.