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Alexander Pinhas,1,2 Jorge S Andrade Romo,1 Giselle Lynch,1,3 Davis B Zhou,1,3 Maria V Castanos Toral,1 Phillip A Tenzel,1 Oscar Otero-Marquez,1 Shoshana Yakubova,1,4 Alexander Barash,1 David Della Rocca,1 Robert Della Rocca,1 Toco YP Chui,1 Richard B Rosen,1 Harsha S Reddy1 1Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, USA; 2Department of Ophthalmology, State University of New York Downstate Medical Center, Brooklyn, NY, USA; 3Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Department of Biology, Macaulay Honors College at City University of New York Queens College, Flushing, NY, USACorrespondence: Harsha S Reddy, Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, 310 E 14th St, New York, NY, 10003, USA, Tel +1 212-979-4284, Fax +1 212-966-6295, Email hreddy@nyee.eduPurpose: Hemodynamic changes surrounding the optic nerve head are known to occur in thyroid-related orbitopathy (TRO). This pilot study explores the capillary and non-capillary peripapillary perfusion changes of the retina in TRO eyes without dysthyroid optic neuropathy (DON) using optical coherence tomography angiography (OCT-A).Methods: Non-capillary and capillary peripapillary perfusion densities were calculated using single 4.5 × 4.5mm en face “RPC layer” OCT-A scans of 8 TRO patients without DON (8 eyes, mean age 40.6 years, range 23– 69 years). Results were compared to a previously published dataset of 133 healthy controls (133 eyes, mean 41.5 years, range 11– 83 years). The strength of association was measured between OCT-A perfusion densities and clinical measures of TRO.Results: Non-capillary peripapillary perfusion density in TRO eyes was found to be significantly decreased compared to healthy controls (TRO group 15.4 ± 2.9% vs controls 21.5 ± 3.1%; p < 0.0001). Capillary peripapillary perfusion densities showed no significant difference (TRO group 42.5 ± 1.8% vs controls 42.5 ± 1.5%; p = 1.0). Clinical measures of disease did not correlate well with OCT-A perfusion densities (p> 0.05).Conclusion: These findings may represent decreased blood flow and subclinical ischemia to the optic nerve. We discuss possible pathogenic mechanisms of thyroid-related vasculopathy, including vessel wall thickening due to immunologically-induced media enlargement.Keywords: thyroid-related orbitopathy, optical coherence tomography angiography, peripapillary microvasculature, thyroid-related vasculopathy

Purpose: to estimate the influence of eye prosthetics on quality of life of patients with anophthalmos and eye subatrophy. Material and methods: 128 patients, 75 men and 53 women, participated in the research. The average age of patients was 59 [48; 70] years. For the assessment of quality of life of patients after eye prosthetics the SF-36 questionnaire, adapted by the International Center for Quality of Life Research was used (St. Petersburg). Results: The research of the quality of life in patients after eye prosthetics and otherwise healthy individuals revealed low quality of life in patients after eye prosthetics both by the integrated indicators of mental (MH) and physical health (PH), and by their constituent scales: physical functioning – PF (U=1620, р=0.04), role-functioning caused by physical condition – RP (U=1552, р=0.02), general health – GH (U=1250, р

Abstract Recent advancements in generative artificial intelligence have enabled analysis of text with visual data, which could have important implications in healthcare. Diagnosis in ophthalmology is often based on a combination of ocular examination, and clinical context. The aim of this study was to evaluate the performance of multimodal GPT-4 (GPT-4 V) in an integrated analysis of ocular images and clinical text. This retrospective study included 40 patients seen in our institution with images of their ocular examinations. Cases were selected by a board-certified ophthalmologist, to represent various pathologies. We provided the model with each patient image, without and then with the clinical context. We also asked two non-ophthalmology physicians to write diagnoses for each image, without and then with the clinical context. Answers for both GPT-4 V and the non-ophthalmologists were evaluated by two board-certified ophthalmologists. Performance accuracies were calculated and compared. GPT-4 V provided the correct diagnosis in 19/40 (47.5%) cases based on images without clinical context, and in 27/40 (67.5%) cases when clinical context was provided. Non-ophthalmologist physicians provided the correct diagnoses in 24/40 (60.0%), and 23/40 (57.5%) of cases without clinical context, and in 29/40 (72.5%) and 27/40 (67.5%) with clinical context. For all study participants adding context improved accuracy (p = 0.033). GPT-4 V is currently able to simultaneously analyze and integrate visual and textual data, and arrive at accurate clinical diagnoses in the majority of cases. Multimodal large language models like GPT-4 V have significant potential to advance both patient care and research in ophthalmology.

Abstract Little attention was given to heparanase 2 (Hpa2) over the last two decades, possibly because it lacks a heparan sulfate (HS)-degrading activity typical of heparanase. Emerging results suggest, nonetheless, that Hpa2 plays a role in human pathologies, including cancer progression where it functions as a tumor suppressor. Here, we examined the role of Hpa2 in cervical carcinoma. We report that high levels of Hpa2 correlate with prolonged survival of cervical carcinoma patients. Strong staining intensity of Hpa2 also correlates with low tumor grade. Overexpression of Hpa2 in SiHa cervical carcinoma cells resulted in tumor xenografts that were two-fold smaller than control tumors. Interestingly, even smaller tumor xenografts were developed by SiHa cells overexpressing the Pro140Arg and Asn543Ile Hpa2 missense mutations that were identified in patients diagnosed with urofacial syndrome (UFS). Utilizing the Ras recruitment system, we identified bromodomain-containing protein 7 (BRD7) to interact with Hpa2 and found that both BRD7 and the Hpa2 mutants are translocated to the cell nucleus in tumors developed by the Pro140Arg and Asn543Ile Hpa2 mutants. Utilizing our newly developed conditional Hpa2-KO mice, we further show that Hpa2 plays a critical role in macrophage polarization; in the absence of Hpa2, macrophages are shifted towards pro-tumorigenic, M2 phenotype. Notably, implanting SiHa cervical carcinoma cells together with Hpa2-KO macrophages promoted tumor growth. These results support, and further expand, the notion that Hpa2 functions as a tumor suppressor, co-operating with another tumor suppressor, BRD7.

ContextPhysiological growth hormone is secreted during slow-wave sleep. Traditionally, growth hormone (GH) therapy is given in daily GH injections before sleep. While morning and evening GH injections produce comparable effects on growth and IGF-1 levels, the evening schedule better imitates the physiological diurnal pattern of GH secretion and action. However, the inflexibility of bedtime injection schedules, coupled with the discomfort and psychological distress associated with the injection and local reaction, may cause sleep disturbances in patients, and may significantly burden them and their families.ObjectiveOur objective was to evaluate evening vs. morning daily GH injections with respect to sleep-wake pattern, duration, and activity index in children treated with growth hormone.DesignAn open-label, randomized crossover trial of 20 children (11 boys) 5–14 years of age with isolated growth hormone deficiency (n=12) and idiopathic short stature (n=8) treated with daily injections of median GH dose 33 (range13-46) mcg/kg/d was performed. Each subject received 2 weeks of evening injections and 2 weeks of morning injections. Patients' sleep-wake patterns and activity index were assessed by a 7-day actigraph covering the second week of each treatment schedule.ResultsAll subjects slept well, within recommended ranges for sleep parameters, regardless of whether they were receiving morning or evening GH injections. Results were comparable for all measures: total time in bed (min), 526.0 ± 51.8 vs 516.9 ± 57.4 for evening and morning GH injections, respectively; total sleep time (min), 512.4 ± 51.1 vs 504.3 ± 57.7; sleep efficiency (%), 93.6 ± 2.6 vs 94.2 ± 2.3; sleep onset latency (min), 8.9 ± 8.1 vs 7.4 ± 6.8; number of arousals per night, 14.5 ± 5.4 vs 12.5 ± 5.2; and 24-hour activity index, 68.3 ± 4.0 vs 67.0 ± 5.0, respectively. No difference was found between the growth hormone deficient and idiopathic short stature group. No difference was found between boys and girls.ConclusionsSleep-wake patterns and activity index were not affected by treatment schedules. We recommend that growth hormone injections take place at any regular time according to the family's convenience.

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.

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.

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.

Abstract Background Building health research capacity in low- and middle-income countries is essential to achieving universal access to safe, high-quality healthcare. It can enable healthcare workers to conduct locally relevant research and apply findings to strengthen their health delivery systems. However, lack of funding, experience, know-how, and weak research infrastructures hinders their ability. Understanding research capacity, engagement, and contextual factors that either promote or obstruct research efforts by healthcare workers can inform national strategies aimed at building research capacity. Methods We used a convergent mixed-methods study design to understand research capacity and research engagement of healthcare workers in Tanzania’s public health system, including the barriers, motivators, and facilitators to conducting research. Our sample included 462 randomly selected healthcare workers from 45 facilities. We conducted surveys and interviews to capture data in five categories: (1) healthcare workers research capacity; (2) research engagement; (3) barriers, motivators, and facilitators; (4) interest in conducting research; and (5) institutional research capacity. We assessed quantitative and qualitative data using frequency and thematic analysis, respectively; we merged the data to identify recurring and unifying concepts. Results Respondents reported low experience and confidence in quantitative (34% and 28.7%, respectively) and qualitative research methods (34.5% and 19.6%, respectively). Less than half (44%) of healthcare workers engaged in research. Engagement in research was positively associated with: working at a District Hospital or above (p = 0.006), having a university degree or more (p = 0.007), and previous research experience (p = 0.001); it was negatively associated with female sex (p = 0.033). Barriers to conducting research included lack of research funding, time, skills, opportunities to practice, and research infrastructure. Motivators and facilitators included a desire to address health problems, professional development, and local and international collaborations. Almost all healthcare workers (92%) indicated interest in building their research capacity. Conclusion Individual and institutional research capacity and engagement among healthcare workers in Tanzania is low, despite high interest for capacity building. We propose a fourfold pathway for building research capacity in Tanzania through (1) high-quality research training and mentorship; (2) strengthening research infrastructure, funding, and coordination; (3) implementing policies and strategies that stimulate engagement; and (4) strengthening local and international collaborations.

The article is devoted to determining the structure of the forensic characteristics of crimes under Article 200 of the Criminal Code of Ukraine “Illegal actions with the documents for transfer, payment cards and other means of access to bank accounts, electronic money, equipment for their production”. The theoretical foundations of developing forensic characteristics of a particular type of crime have been analysed and the grounds for forming its structure have been highlighted. These grounds include criminal law elements of a crime, a list of circumstances to be proved in criminal proceedings, and elements of the mechanism of committing illegal actions with payment instruments. Significant elements for the forensic methodology of the criminal law characteristics of the crime under investigation are its subject matter, method of commission and subjective features. Among the elements of the subject matter of proof, the most important are also the object, method and identity of the offender, as well as the time, place and other circumstances of the crime. In turn, the mechanism of illegal actions with payment instruments determines the need to study these elements in their broadest sense, i.e., taking into account all stages of criminal activity (preparation, direct commission and concealment), means and conditions of its implementation. Based on the analysis of the above theoretical foundations for the formation of a forensic characteristic of this type of crime, the author identifies the following elements which should be included in its structure: the subject matter of the crime; the method of the crime and its links with other criminal offences; typical traces (trace pattern); the setting (conditions) of the crime; and the identity of the perpetrator. This structure is the most optimal one, allowing for a comprehensive analysis of the typical features of the crime mechanism and building its qualitative information model as the basis for further development of the relevant separate forensic methodology.

IntroductionThe field of vestibular science, encompassing the study of the vestibular system and associated disorders, has experienced notable growth and evolving trends over the past five decades. Here, we explore the changing landscape in vestibular science, focusing on epidemiology, peripheral pathologies, diagnosis methods, treatment, and technological advancements.MethodsPublication data was obtained from the US National Center for Biotechnology Information (NCBI) PubMed database. The analysis included epidemiological, etiological, diagnostic, and treatment-focused studies on peripheral vestibular disorders, with a particular emphasis on changes in topics and trends of publications over time.ResultsOur dataset of 39,238 publications revealed a rising trend in research across all age groups. Etiologically, benign paroxysmal positional vertigo (BPPV) and Meniere’s disease were the most researched conditions, but the prevalence of studies on vestibular migraine showed a marked increase in recent years. Electronystagmography (ENG)/ Videonystagmography (VNG) and Vestibular Evoked Myogenic Potential (VEMP) were the most commonly discussed diagnostic tools, while physiotherapy stood out as the primary treatment modality.ConclusionOur study presents a unique opportunity and point of view, exploring the evolving landscape of vestibular science publications over the past five decades. The analysis underscored the dynamic nature of the field, highlighting shifts in focus and emerging publication trends in diagnosis and treatment over time.

The major vault protein (MVP) mediates diverse cellular responses, including cancer cell resistance to chemotherapy and protection against inflammatory responses to Pseudomonas aeruginosa Here, we report the use of photoactive probes to identify MVP as a target of the N-(3-oxo-dodecanoyl) homoserine lactone (C12), a quorum sensing signal of certain proteobacteria including P. aeruginosa. A treatment of normal and cancer cells with C12 or other N-acyl homoserine lactones (AHLs) results in rapid translocation of MVP into lipid raft (LR) membrane fractions. Like AHLs, inflammatory stimuli also induce LR-localization of MVP, but the C12 stimulation reprograms (functionalizes) bioactivity of the plasma membrane by recruiting death receptors, their apoptotic adaptors, and caspase-8 into LR. These functionalized membranes control AHL-induced signaling processes, in that MVP adjusts the protein kinase p38 pathway to attenuate programmed cell death. Since MVP is the structural core of large particles termed vaults, our findings suggest a mechanism in which MVP vaults act as sentinels that fine-tune inflammation-activated processes such as apoptotic signaling mediated by immunosurveillance cytokines including tumor necrosis factor-related apoptosis inducing ligand (TRAIL).