Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV-1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion-stabilized HIV-1 envelope (Env) trimer, BG505 DS-SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4-binding site (CD4bs) of vulnerability. Two of the vaccine-elicited CD4bs-targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a-hinge region and human IgG1-constant region (G36×3-IgG2a and R27×3-IgG2a), neutralized 96% of a multiclade 208-strain panel at geometric mean IC80s of 0.314 and 0.033 µg mL-1, respectively. Cryo-EM structures of these nanobodies in complex with Env trimer revealed the two nanobodies to neutralize HIV-1 by mimicking the recognition of the CD4 receptor. To enhance their neutralizing potency and breadth, nanobodies are linked to the light chain of the V2-apex-targeting broadly neutralizing antibody, CAP256V2LS. The resultant human-llama bispecific antibody CAP256L-R27×3LS exhibited ultrapotent neutralization and breadth exceeding other published HIV-1 broadly neutralizing antibodies, with pharmacokinetics determined in FcRn-Fc mice similar to the parent CAP256V2LS. Vaccine-elicited llama nanobodies, when combined with V2-apex broadly neutralizing antibodies, may therefore be able to fulfill anti-HIV-1 therapeutic and prophylactic clinical goals.

Large language models (LLMs) are transformer-based neural networks that can provide human-like responses to questions and instructions. LLMs can generate educational material, summarize text, extract structured data from free text, create reports, write programs, and potentially assist in case sign-out. LLMs combined with vision models can assist in interpreting histopathology images. LLMs have immense potential in transforming pathology practice and education, but these models are not infallible, so any artificial intelligence generated content must be verified with reputable sources. Caution must be exercised on how these models are integrated into clinical practice, as these models can produce hallucinations and incorrect results, and an over-reliance on artificial intelligence may lead to de-skilling and automation bias. This review paper provides a brief history of LLMs and highlights several use cases for LLMs in the field of pathology.

To expand the knowledge about common diseases in llamas and alpacas in Germany, a screening of the cases of South American camelids presented at the Clinic for Swine and Small Ruminants of the University of Veterinary Medicine Hannover, Germany from 2005 to the end of November 2021 was performed. A retrospective evaluation of necropsy reports from this period was conducted. Overall, necropsy reports were evaluated from 187 alpacas, 35 llamas and one vicuña (n = 223). A total of 50.2% of the dissected animals were thin or cachectic. Pathological alterations of the gastrointestinal tract were the most common findings (44.8%). In addition, liver changes were recorded, most frequently in adult animals. In contrast, diseases of the respiratory tract and the nervous system were found more frequently in juvenile animals. This study provides an overview of common pathologies in South American camelids in Germany and thus may help to recognise different disease symptoms at an early stage.

BACKGROUND: Iatrogenic blood contamination during cerebrospinal fluid (CSF) centesis is common, which can limit the diagnostic usefulness of the sample. A novel ultrasound-guided CSF collection technique is described in horses, by which CSF is obtained from the atlantoaxial (AA) space.
OBJECTIVE: To compare ultrasound-guided AA centesis with lumbosacral (LS) centesis in South American camelids (SAC). The hypotheses were that AA centesis would yield samples with less blood contamination although being technically more challenging than LS centesis.
METHODS: Eight clinically healthy adult SAC from a university-owned teaching herd.
METHODS: Single-blinded, randomized, 4-way, 4-period crossover study in which 2 veterinarians each performed both centesis techniques on each animal once. Cytological sample analysis was performed, and the technical difficulty of sample acquisition was assessed.
RESULTS: The CSF was collected successfully and without complications by either technique during all collection attempts. Aspects of technical difficulty and concentrations of CSF analytes did not vary significantly between techniques. Median total nucleated cell and red blood cell counts were 1/μL and 0.5/μL and 167.5/μL and 155/μL for AA and LS techniques, respectively. The median total protein concentration was 32.9 mg/dL and 38 mg/dL for AA and LS centeses. A median of 1 attempt was necessary for both centesis techniques and the median number of needle repositioning events was 1 for AA and 0 for LS.
CONCLUSIONS: Depending on clinical circumstances, ultrasound-guided AA centesis appears to be an acceptable alternative to other techniques for collection of CSF from SAC.

The breeding of South American Camelids (SACs), particularly llamas and alpacas, is becoming increasingly popular in regions that are not their natural habitat, including Europe. These animals are considered to be relatively disease resistant. However, due to their growing popularity, special attention should be given to infections in llamas and alpacas. Knowledge of bacterial infections is very important to veterinarians and breeders. Many of these diseases also have zoonotic potential, so these animals must be considered as sources of potential zoonotic infections. Due to the limited information on many diseases occurring in llamas and alpacas, veterinarians often rely on data collected in other animal species, focusing on cattle, sheep and horses. This work aims to summarise the knowledge of diseases caused by Clostridium spp., Mycobacterium tuberculosis complex, Mycobacterium avium subsp. paratuberculosis, Streptococcus spp., Escherichia coli, Pasteurella multocida, Manheimia haemolytica and Corynebacterium pseudotuberculosis in llamas and alpacas, with particular attention to epidemiology, clinical signs and diagnostics.

South American camelids (SACs) play an increasing role in veterinary care in Europe. Many alpacas or llamas presented to veterinarians suffer from anaemia, regularly with a packed cell volume (PCV) below 0.10 l/l, which is a life-threatening condition for the animals. This review article presents clinical and laboratory diagnostic tools for the diagnosis of anaemia in SACs. Clinical identification of anaemic animals can be performed by assessing the FAMACHA© score and the Body Condition Score (BCS), since anaemia in alpacas and llamas correlates with pale mucous membranes and a lowered BCS. Haematological examination of a blood sample can provide a more differentiated diagnosis of anaemia in SACs. A common finding is regenerative anaemia with an increased number of reticulocytes that is often caused by blood loss due to Haemonchus contortus. Changes in a blood smear from an alpaca or llama with regenerative anaemia may include normoblasts (nucleated red blood cells), anisocytosis, poikilocytosis, polychromasia, Howell-Jolly bodies or basophilic stippling. Furthermore, non-regenerative anaemia, often caused by trace element deficiency or cachexia, can also occur.

BACKGROUND: Alpaca (Vicugna pacos), llama (Lama glama), vicugna (Vicugna vicugna) and guanaco (Lama guanicoe), are the camelid species distributed over the Andean high-altitude grasslands, the Altiplano, and the Patagonian arid steppes. Despite the wide interest on these animals, most of the loci under selection are still unknown. Using whole-genome sequencing (WGS) data we investigated the occurrence and the distribution of Runs Of Homozygosity (ROHs) across the South American Camelids (SACs) genome to identify the genetic relationship between the four species and the potential signatures of selection.
RESULTS: A total of 37 WGS samples covering the four species was included in the final analysis. The multi-dimensional scaling approach showed a clear separation between the four species; however, admixture analysis suggested a strong genetic introgression from vicugna and llama to alpaca. Conversely, very low genetic admixture of the guanaco with the other SACs was found. The four species did not show significant differences in the number, length of ROHs (100-500 kb) and genomic inbreeding values. Longer ROHs (> 500 kb) were found almost exclusively in alpaca. Seven overlapping ROHs were shared by alpacas, encompassing nine loci (FGF5, LOC107034918, PRDM8, ANTXR2, LOC102534792, BSN, LOC116284892, DAG1 and RIC8B) while nine overlapping ROHs were found in llama with twenty-five loci annotated (ERC2, FZD9, BAZ1B, BCL7B, LOC116284208, TBL2, MLXIPL, PHF20, TRNAD-AUC, LOC116284365, RBM39, ARFGEF2, DCAF5, EXD2, HSPB11, LRRC42, LDLRAD1, TMEM59, LOC107033213, TCEANC2, LOC102545169, LOC116278408, SMIM15, NDUFAF2 and RCOR1). Four overlapping ROHs, with three annotated loci (DLG1, KAT6B and PDE4D) and three overlapping ROHs, with seven annotated genes (ATP6V1E1, BCL2L13, LOC116276952, BID, KAT6B, LOC116282667 and LOC107034552), were detected for vicugna and guanaco, respectively.
CONCLUSIONS: The signatures of selection revealed genomic areas potentially selected for production traits as well as for natural adaptation to harsh environment. Alpaca and llama hint a selection driven by environment as well as by farming purpose while vicugna and guanaco showed selection signals for adaptation to harsh environment. Interesting, signatures of selection on KAT6B gene were identified for both vicugna and guanaco, suggesting a positive effect on wild populations fitness. Such information may be of interest to further ecological and animal production studies.

Objective The primary aim of this research was to address the limitations observed in the medical knowledge of prevalent large language models (LLMs) such as ChatGPT, by creating a specialized language model with enhanced accuracy in medical advice. Methods We achieved this by adapting and refining the large language model meta-AI (LLaMA) using a large dataset of 100,000 patient-doctor dialogues sourced from a widely used online medical consultation platform. These conversations were cleaned and anonymized to respect privacy concerns. In addition to the model refinement, we incorporated a self-directed information retrieval mechanism, allowing the model to access and utilize real-time information from online sources like Wikipedia and data from curated offline medical databases. Results The fine-tuning of the model with real-world patient-doctor interactions significantly improved the model\'s ability to understand patient needs and provide informed advice. By equipping the model with self-directed information retrieval from reliable online and offline sources, we observed substantial improvements in the accuracy of its responses. Conclusion Our proposed ChatDoctor, represents a significant advancement in medical LLMs, demonstrating a significant improvement in understanding patient inquiries and providing accurate advice. Given the high stakes and low error tolerance in the medical field, such enhancements in providing accurate and reliable information are not only beneficial but essential.

Middle East respiratory syndrome coronavirus (MERS-CoV) infection can cause fatal pulmonary inflammatory disease in humans. Contrarily, camelids and bats are the main reservoir hosts, tolerant for MERS-CoV replication without suffering clinical disease. Here, we isolated cervical lymph node (LN) cells from MERS-CoV convalescent llamas and pulsed them with two different viral strains (clades B and C). Viral replication was not supported in LN, but a cellular immune response was mounted. Reminiscent Th1 responses (IFN-γ, IL-2, IL-12) were elicited upon MERS-CoV sensing, accompanied by a marked and transient peak of antiviral responses (type I IFNs, IFN-λ3, ISGs, PRRs and TFs). Importantly, expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8) or inflammasome components (NLRP3, CASP1, PYCARD) was dampened. The role of IFN-λ3 to counterbalance inflammatory processes and bridge innate and adaptive immune responses in camelid species is discussed. Our findings shed light into key mechanisms on how reservoir species control MERS-CoV in the absence of clinical disease.

Natural language processing (NLP) has been studied in computing for decades. Recent technological advancements have led to the development of sophisticated artificial intelligence (AI) models, such as Chat Generative Pre-trained Transformer (ChatGPT). These models can perform a range of language tasks and generate human-like responses, which offers exciting prospects for academic efficiency. This manuscript aims at (i) exploring the potential benefits and threats of ChatGPT and other NLP technologies in academic writing and research publications; (ii) highlights the ethical considerations involved in using these tools, and (iii) consider the impact they may have on the authenticity and credibility of academic work. This study involved a literature review of relevant scholarly articles published in peer-reviewed journals indexed in Scopus as quartile 1. The search used keywords such as \"ChatGPT,\" \"AI-generated text,\" \"academic writing,\" and \"natural language processing.\" The analysis was carried out using a quasi-qualitative approach, which involved reading and critically evaluating the sources and identifying relevant data to support the research questions. The study found that ChatGPT and other NLP technologies have the potential to enhance academic writing and research efficiency. However, their use also raises concerns about the impact on the authenticity and credibility of academic work. The study highlights the need for comprehensive discussions on the potential use, threats, and limitations of these tools, emphasizing the importance of ethical and academic principles, with human intelligence and critical thinking at the forefront of the research process. This study highlights the need for comprehensive debates and ethical considerations involved in their use. The study also recommends that academics exercise caution when using these tools and ensure transparency in their use, emphasizing the importance of human intelligence and critical thinking in academic work.