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Cannabis use disorder (CanUD) has increased with the legalization of the use of cannabis. Around 20% of individuals using cannabis develop CanUD, and the number of users has grown with increasing ease of access. CanUD and other substance use disorders (SUDs) are associated phenotypically and genetically. We leveraged new CanUD genomics data to undertake genetically-informed analyses with unprecedented power, to investigate the genetic architecture and causal relationships between CanUD and lifetime cannabis use with risk for developing SUDs and substance use traits. Analyses included calculating local and global genetic correlations, genomic structural equation modeling (genomicSEM), and Mendelian Randomization (MR). Results from the genetic correlation and genomicSEM analyses demonstrated that CanUD and cannabis use differ in their relationships with SUDs and substance use traits. We found significant causal effects of CanUD influencing all the analyzed traits: opioid use disorder (OUD) (Inverse variant weighted, IVW β = 0.925 ± 0.082), problematic alcohol use (PAU) (IVW β = 0.443 ± 0.030), drinks per week (DPW) (IVW β = 0.182 ± 0.025), Fagerström Test for Nicotine Dependence (FTND) (IVW β = 0.183 ± 0.052), cigarettes per day (IVW β = 0.150 ± 0.045), current versus former smokers (IVW β = 0.178 ± 0.052), and smoking initiation (IVW β = 0.405 ± 0.042). We also found evidence of bidirectionality showing that OUD, PAU, smoking initiation, smoking cessation, and DPW all increase risk of developing CanUD. For cannabis use, bidirectional relationships were inferred with PAU, smoking initiation, and DPW; cannabis use was also associated with a higher risk of developing OUD (IVW β = 0.785 ± 0.266). GenomicSEM confirmed that CanUD and cannabis use load onto different genetic factors. We conclude that CanUD and cannabis use can increase the risk of developing other SUDs. This has substantial public health implications; the move towards legalization of cannabis use may be expected to increase other kinds of problematic substance use. These harmful outcomes are in addition to the medical harms associated directly with CanUD.

BackgroundPatients find technology tools to be more approachable for seeking sensitive health-related information, such as reproductive health information. The inventive conversational ability of artificial intelligence (AI) chatbots, such as ChatGPT (OpenAI Inc), offers a potential means for patients to effectively locate answers to their health-related questions digitally.ObjectiveA pilot study was conducted to compare the novel ChatGPT with the existing Google Search technology for their ability to offer accurate, effective, and current information regarding proceeding action after missing a dose of oral contraceptive pill.MethodsA sequence of 11 questions, mimicking a patient inquiring about the action to take after missing a dose of an oral contraceptive pill, were input into ChatGPT as a cascade, given the conversational ability of ChatGPT. The questions were input into 4 different ChatGPT accounts, with the account holders being of various demographics, to evaluate potential differences and biases in the responses given to different account holders. The leading question, "what should I do if I missed a day of my oral contraception birth control?" alone was then input into Google Search, given its nonconversational nature. The results from the ChatGPT questions and the Google Search results for the leading question were evaluated on their readability, accuracy, and effective delivery of information.ResultsThe ChatGPT results were determined to be at an overall higher-grade reading level, with a longer reading duration, less accurate, less current, and with a less effective delivery of information. In contrast, the Google Search resulting answer box and snippets were at a lower-grade reading level, shorter reading duration, more current, able to reference the origin of the information (transparent), and provided the information in various formats in addition to text.ConclusionsChatGPT has room for improvement in accuracy, transparency, recency, and reliability before it can equitably be implemented into health care information delivery and provide the potential benefits it poses. However, AI may be used as a tool for providers to educate their patients in preferred, creative, and efficient ways, such as using AI to generate accessible short educational videos from health care provider-vetted information. Larger studies representing a diverse group of users are needed.

One of the justifiable criticisms of human genetic studies is the underrepresentation of participants from diverse populations. Lack of inclusion must be addressed at-scale to identify causal disease factors and understand the genetic causes of health disparities. We present genome-wide associations for 2068 traits from 635,969 participants in the Department of Veterans Affairs Million Veteran Program, a longitudinal study of diverse United States Veterans. Systematic analysis revealed 13,672 genomic risk loci; 1608 were only significant after including non-European populations. Fine-mapping identified causal variants at 6318 signals across 613 traits. One-third (n = 2069) were identified in participants from non-European populations. This reveals a broadly similar genetic architecture across populations, highlights genetic insights gained from underrepresented groups, and presents an extensive atlas of genetic associations.

PURPOSE: The specialty of Laboratory Genetics and Genomics (LGG) was created in 2017 in an effort to reflect the increasing convergence in technologies and approaches between clinical molecular genetics and clinical cytogenetics. However, there has not yet been any formal evaluation of the merging of these disciplines and the challenges faced by Program Directors (PDs) tasked with ensuring the successful training of laboratory geneticists under the new model. METHODS: An electronic multi-question Qualtrics survey was created and was sent to the PD for each of the Accreditation Council for Graduate Medical Education-accredited LGG fellowship programs at the time. The data were collected, and the responses were aggregated for each question. RESULTS: All of the responding PDs had started training at least 1 LGG fellow. PDs noted challenges with funding, staff shortages, molecular/cytogenetics content integration, limited total training time, increased remote work, increased sendout testing, and a lack of prior cytogenetics knowledge among incoming fellows. CONCLUSION: This survey attempted to assess the challenges that LGG PDs have been facing in offering and integrating clinical molecular genetics and clinical cytogenetics fellowship training. Common challenges between programs were noted, and a set of 6 concluding comments are provided to facilitate future discussion.

Abstract Background Vector-borne pathogens (VBPs) are increasing in significance in veterinary medicine and public health settings, with wildlife playing a potentially crucial role in their transmission. Eurasian badgers (Meles meles) are widely distributed across Europe. However, information currently available on the prevalence of VBPs in badgers is limited. The objective of the current study was to investigate the occurrence of Anaplasmataceae, Bartonella spp., Mycoplasma spp., Rickettsia spp., Piroplasmida, Trypanosomatida and Filarioidea in badgers and subsequently, based on the results, assess the potential risk to domestic animals, other wildlife and humans. Methods Between 2017 and 2021, blood or spleen samples from 220 badgers were collected in nine continental European countries: Austria (n = 7), Bosnia and Herzegovina (n = 2), Croatia (n = 22), France (n = 44), Germany (n = 16), Hungary (n = 7), Italy (n = 16), Romania (n = 80) and Serbia (n = 26). VBPs were identified by performing PCR analysis on the samples, followed by Sanger sequencing. Additionally, to distinguish between different Babesia lineages we performed restriction fragment length polymorphism (RFLP) analysis on piroplasm-positive samples, using HinfI as restriction enzyme. A phylogenetic analysis was performed on Mycoplasma spp. Results The pathogens identified were Babesia sp. badger type A (54%), B (23%), and C (37%); Trypanosoma pestanai (56%); Mycoplasma sp. (34%); Candidatus Mycoplasma haematomelis (8%); Candidatus Mycoplasma haematominutum (0.5%); and Ehrlichia spp. (2%). Rickettsia spp., Bartonella spp. and filarioid nematodes were not detected among the tested samples. Conclusions The large sample size and diverse study populations in this study provide valuable insights into the distribution and epidemiology of the analyzed pathogens. Some of the VBPs identified in our study show high similarity to those found in domestic animals, such as dogs. This finding suggests that badgers, as potential reservoirs for these pathogens, may pose a threat not only to other wildlife but also to domestic animals in close vicinity. Continuous surveillance is essential to monitor VBPs in wildlife as a means to enable the assessment of their impact on other wildlife species, domestic animals and human health. Graphical Abstract

Abstract Background Angiostrongylus vasorum, commonly known as the “French heartworm,” is a nematode belonging to the Metastrongyloidea superfamily. This parasite was first identified in Toulouse, France in 1853 infecting the pulmonary arteries and the right side of the heart of a Pointer dog. Angiostrongylosis is an important infection due its severe clinical signs and potential for causing high morbidity and mortality in domestic dogs. This nematode has not been studied in Algeria. The aim of this study was investigate the presence of lungworms among different mammal species in a number of Algerian regions. Methods Between February 2022 and September 2023, 47 road-killed animals were collected from six administrative units (departments) in Algeria. All carcasses underwent a full parasitological necropsy, and lung tissues were preserved in 10% buffered formalin and concentrated ethanol for further study. All collected samples were subjected to histological and PCR (cytochrome c oxidase subunit 1 gene) analyses for lungworm identification. Results Histological examination revealed the presence of nematode eggs and larvae in the alveolar space and chronic obstructive vascular changes were detected in a single golden African wolf (Canis lupaster) collected from the department of Constantine. First-stage larvae were collected and morphologically identified as Angiostrongylus spp. The molecular identification confirmed the presence of A. vasorum. All other animals tested were negative for lungworms. Conclusions To the best of our knowledge, this is the first report of A. vasorum infection in an African golden wolf (Canis lupaster). We report a new host association, highlighting the importance of further studies to update the geographical distribution of A. vasorum and its epidemiology across Algeria. Graphical Abstract

As recreational use of cannabis is being decriminalized in many places and medical use widely sanctioned, there are growing concerns about increases in cannabis use disorder (CanUD), which is associated with numerous medical comorbidities. Here we performed a genome-wide association study of CanUD in the Million Veteran Program (MVP), followed by meta-analysis in 1,054,365 individuals (ncases = 64,314) from four broad ancestries designated by the reference panel used for assignment (European n = 886,025, African n = 123,208, admixed American n = 38,289 and East Asian n = 6,843). Population-specific methods were applied to calculate single nucleotide polymorphism-based heritability within each ancestry. Statistically significant single nucleotide polymorphism-based heritability for CanUD was observed in all but the smallest population (East Asian). We discovered genome-wide significant loci unique to each ancestry: 22 in European, 2 each in African and East Asian, and 1 in admixed American ancestries. A genetically informed causal relationship analysis indicated a possible effect of genetic liability for CanUD on lung cancer risk, suggesting potential unanticipated future medical and psychiatric public health consequences that require further study to disentangle from other known risk factors such as cigarette smoking.

Problematic alcohol use (PAU), a trait that combines alcohol use disorder and alcohol-related problems assessed with a questionnaire, is a leading cause of death and morbidity worldwide. Here we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals (European, N = 903,147; African, N = 122,571; Latin American, N = 38,962; East Asian, N = 13,551; and South Asian, N = 1,716 ancestries). We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by a computational drug repurposing analysis. Cross-ancestry polygenic risk scores showed better performance of association in independent samples than single-ancestry polygenic risk scores. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. This study advances our knowledge of the genetic etiology of PAU, and these findings may bring possible clinical applicability of genetics insights-together with neuroscience, biology and data science-closer.

Src family kinases (SFKs) are evolutionarily conserved proteins acting downstream of receptors and regulating cellular processes including proliferation, adhesion, and migration. Elevated SFK expression and activity correlate with progression of a variety of cancers. Here, using the Drosophila melanogaster border cells as a model, we report that localized activation of a Src kinase promotes an unusual behavior: engulfment of one cell by another. By modulating Src expression and activity in the border cell cluster, we found that increased Src kinase activity, either by mutation or loss of a negative regulator, is sufficient to drive one cell to engulf another living cell. We elucidate a molecular mechanism that requires integrins, the kinases SHARK and FAK, and Rho family GTPases, but not the engulfment receptor Draper. We propose that cell cannibalism is a result of aberrant phagocytosis, where cells with dysregulated Src activity fail to differentiate between living and dead or self versus non-self, thus driving this malignant behavior.

Abstract There is a high prevalence of antisocial personality disorder (ASPD) in individuals affected by substance use disorders (SUD). However, there is limited information on the specific patterns of association of ASPD with SUD severity and specific SUD diagnostic criteria. We investigated the association of alcohol, cannabis, cocaine, opioid, and tobacco use disorders (AUD, CanUD, CocUD, OUD, and TUD, respectively) in 1660 individuals with ASPD and 6640 controls matched by sex (24% female), age, and racial/ethnic background in a sample ascertained for addiction-related traits. Generalized linear regressions were used to test ASPD with respect to the five DSM-5 SUD diagnoses, their severity (i.e., mild, moderate, severe), and their diagnostic criteria. We found that ASPD is associated with the diagnosis and severity of AUD (Odds Ratio, ORs = 1.89 and 1.25), CanUD (ORs = 2.13 and 1.32), and TUD (ORs = 1.50 and 1.21) (ps

Abstract To investigate quantitative associations between AI-assessed disease activity and optical coherence tomography angiography (OCTA)-derived parameters in patients with neovascular age-related macular degeneration (nAMD) undergoing anti-VEGF therapy. OCTA and SD-OCT images obtained from multicenter, randomized study data were evaluated. A deep learning algorithm (RetInSight) was used to detect and quantify macular fluid on SD-OCT. Mixed effects models were applied to evaluate correlations between fluid volumes, macular neovascularization (MNV)-type and OCTA-derived MNV parameters; lesion size (LS) and vessel area (NVA). 230 patients were included. A significant positive correlation was observed between SRF and NVA (estimate = 199.8 nl/mm2, p = 0.023), while a non-significant but negative correlation was found between SRF and LS (estimate = − 71.3 nl/mm2, p = 0.126). The presence of Type I and Type II MNV was associated with significantly less intraretinal fluid (IRF) compared to Type III MNV (estimate type I:− 52.1 nl, p = 0.019; estimate type II:− 51.7 nl, p = 0.021). A significant correlation was observed between pigment epithelial detachment (PED) and the interaction between NVA and LS (estimate:28.97 nl/mm2; p = 0.012). Residual IRF at week 12 significantly correlated to baseline NVA (estimate:38.1 nl/mm2; p = 0.015) and LS (estimate:− 22.6 nl/mm2; p = 0.012). Fluid in different compartments demonstrated disparate associations with MNV OCTA features. While IRF at baseline was most pronounced in type III MNV, residual IRF was driven by neovascular MNV characteristics. Greater NVA in proportion to LS was associated with higher amounts of SRF and PED. The correlation between these parameters may represent MNV maturation and can be used as a biomarker for resolution of disease activity. AI-based OCT analysis allows for a deeper understanding of neovascular disease in AMD and the potential to adjust therapeutic strategies to optimize outcomes through precision medicine.

Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (rg = 0.16 ± 0.04; p = 0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.

The implementation of cancer immunotherapies has seen limited clinical success in head and neck squamous cell carcinoma (HNSCC). Interleukin-2 (IL-2), which modulates the survival and functionality of lymphocytes, is an attractive target for new immunotherapies but one that is limited by presence of regulatory T cells (Tregs) expressing the high-affinity IL-2Rα. The bispecific immunocytokine PD1-IL2v preferentially delivers IL-2 signaling through IL-2Rβγ on PD-1-expressing cells. Selectively targeting the intermediate-affinity IL-2Rβγ can be leveraged to induce anti-tumor immune responses in effector T cells and natural killer (NK) cells while limiting the negative regulation of IL-2Rα activation on Tregs. Using radiation therapy (RT) in combination with PD1-IL2v improves local tumor control and survival, and controls metastatic spread in orthotopic HNSCC tumor models. PD1-IL2v drives systemic activation and expansion of circulating and tumor-infiltrating cytotoxic T cells and NK cells while limiting Treg-mediated immunosuppression. These data show that PD1-L2v induces durable systemic tumor control in HNSCC.

Reptiles are among the most diverse groups of animals, inhabiting nearly all continents and environments. Understanding their parasite biodiversity has garnered significant interest, particularly from a One Health perspective. Although the highly diverse reptile fauna of Iran, comprising 272 species i.e. 89 snakes (Serpentes), 171 lizards (Sauria), 8 turtles, 2 tortoises (Testudines), 1 crocodile (Crocodilia), and 1 worm-lizard (Amphisbaenia), there is a shortage of information about parasites. The present review is a compilation of 62 studies published from 1922 to August 2024. We present information on 56 species of reptiles from five groups (amphisbaenians, crocodiles, testudines, snakes, and lizards) and 98 parasitic taxa belonging to different protozoa and metazoa i.e. nematodes, cestodes, trematodes, acanthocephala, leeches, ticks, mites, and myiasis -producing flies. Although 63 taxa were diagnosed at the species level, 35 parasite taxa were only reported at the genus or family levels. Reviewing the literature, we found a paucity of information about endemic reptiles several of which are vulnerable species. Considering that some of the detected parasites e.g. Cryptosporidium and amoebae have serious clinical and/or public health threats molecular diagnostic techniques are needed for precise identification and understanding of the epidemiology and the potential zoonotic implications associated with parasites of reptiles. There is also a need to understand the exact distribution and host-parasite associations in different reptilian species present in Iran including the role of the reptiles as intermediate and reservoir hosts.

With the development of technology, artificial intelligence has become an important factor nowadays, while the field of cryptocurrencies has become an increasingly interesting topic for investors. For these reasons, artificial intelligence has started to be used in investments, because it offers a more detailed analysis of the data, of the current situation in the market without emotional involvement. The risk of making errors is also reduced and the level of security improves. This paper analyzes the connection between investment risk and the use of artificial intelligence in the field of cryptocurrencies. For a better understanding of this aspect, a bibliometric analysis was carried out to highlight the link between investments and artificial intelligence. Aspects related to the co-occurrence of keywords and co-authorship between countries were analyzed, and the results highlighted the fact that a developed economy in which there is constant investment is more often addressing topics related to artificial intelligence and investment risk, and individuals are increasingly starting to use artificial intelligence when choosing to invest in areas such as cryptocurrencies, because they receive information that helps them reduce the risk to which they are exposed.

The digital age has ushered in profound changes across various sectors, particularly in finance. Digitalization has transformed consumer behavior, introducing novel ways for individuals to manage and interact with their finances through digital money and cryptocurrencies. This abstract explores the intersection of digitalization, consumer behavior, and the emergence of digital currencies, emphasizing the implications and trends in this rapidly evolving landscape. The rise of cryptocurrencies, such as Bitcoin and Ethereum, has not only revolutionized the financial industry but has also sparked interest in understanding the factors driving their adoption and usage. These digital assets operate on blockchain technology, providing transparency and security, which are crucial in fostering consumer trust. However, the volatility and regulatory uncertainties surrounding cryptocurrencies pose challenges that need to be addressed to ensure their sustainable integration into the financial system. This article delves into these themes, presenting a comprehensive overview of the current state of digital money and cryptocurrencies. It also includes a case study based on a bibliometric analysis of research focused on cryptocurrencies. The case study aims to identify key trends, influential works, and emerging topics in this field, offering valuable insights into the academic and practical implications of cryptocurrency adoption.