The Era of 1-bit LLMs: All Large Language Models are in 1.58 Bits

Recent research, such as BitNet, is paving the way for a new era of 1-bit Large Language Models (LLMs). In this work, we introduce a 1-bit LLM variant, namely BitNet b1.58, in which every single parameter (or weight) of the LLM is ternary {-1, 0, 1}. It matches the full-precision (i.e., FP16 or BF16) Transformer LLM with the same model size and training tokens in terms of both perplexity and end-task performance, while being significantly more cost-effective in terms of latency, memory, throughput, and energy consumption. More profoundly, the 1.58-bit LLM defines a new scaling law and recipe for training new generations of LLMs that are both high-performance and cost-effective. Furthermore, it enables a new computation paradigm and opens the door for designing specific hardware optimized for 1-bit LLMs.Comment: Work in progres

Postoperative serum squamous cell carcinoma antigen and carcinoembryonic antigen predict overall survival in surgical patients with esophageal squamous cell carcinoma

BackgroundTumor markers are routinely used in clinical practice. However, for resectable patients with esophageal squamous cell carcinoma (ESCC), they are applied infrequently as their prognostic significance is incompletely understood.MethodsThis historical cohort study included 2769 patients with resected ESCC from 2011 to 2018 in a high-risk area in northern China. Their clinical data were extracted from the Electronic Medical Record. Survival analysis of eight common tumor markers was performed with multivariable Cox proportional hazards regressions.ResultsWith a median follow-up of 39.5 months, 901 deaths occurred. Among the eight target markers, elevated postoperative serum SCC (Squamous cell carcinoma antigen) and CEA (Carcinoembryonic antigen) predicted poor overall survival (SCC HRadjusted: 2.67, 95% CI: 1.70-4.17; CEA HRadjusted: 2.36, 95% CI: 1.14-4.86). In contrast, preoperative levels were not significantly associated with survival. Stratified analysis also demonstrated poorer survival in seropositive groups of postoperative SCC and CEA within each TNM stage. The above associations were generally robust using different quantiles of concentrations above the upper limit of the clinical normal range as alternative cutoffs. Regarding temporal trends of serum levels, SCC and CEA were similar. Their concentrations fell rapidly after surgery and thereafter remained relatively stable.ConclusionPostoperative serum SCC and CEA levels predict the overall survival of ESCC surgical patients. More importance should be attached to the use of these markers in clinical applications

Mycobacterium marinum hand infection: a case report and literature review

Mycobacterium marinum, a photochromogenic, slow-growing mycobacterium, thrives in both marine and freshwater environments. Optimal growth occurs between 25°C and 35°C, with survival becoming challenging above 37°C. Typically, M. marinum enters the body via skin abrasions, often leading to infections of the upper extremities. Diagnosis of M. marinum infection is frequently challenging and delayed due to the difficult pathogen identification. At present, a standardized treatment protocol has yet to be established. Presented herein is a case study detailing an infection of the right hand's middle finger caused by M. marinum. Notably, his occupation as a chef, handling fish and seafood post-injury, was a significant factor. Histological examination of the skin biopsy and positive acid-fast staining were consistent with a diagnosis of mycobacterial infection. Pathological examination confirmed a skin infection with infectious granuloma, and tissue section acid-fast staining revealed acid-fast bacill. Cultures on Columbia blood agar yielded rough, flattened, yellow-fleshy colonies after 10 days, which was identified as M. marinum through 16S rRNA sequencing. The patient responded well to a 3-month regimen of oral moxifloxacin (0.4 qd) and linezolid (0.6 qd), resulting in rash resolution and pain relief, with no recurrence observed for 1-year follow-up. This report presents the first documented acid-fast staining images of M. marinum tissue sections and colony morphology photographs, offering an in-depth view of M. marinum's morphological characteristics. It aims to enhance awareness of M. marinum infections, underscore the necessity for clinicians to delve into patient histories, and provide a review of the clinical manifestations, diagnostic techniques, therapeutic approaches, and pathogenic mechanisms associated with M. marinum

The Epitope and Neutralization Mechanism of AVFluIgG01, a Broad-Reactive Human Monoclonal Antibody against H5N1 Influenza Virus

The continued spread of highly pathogenic avian influenza (HPAI) H5N1 virus underscores the importance of effective antiviral approaches. AVFluIgG01 is a potent and broad-reactive H5N1-neutralizing human monoclonal antibody (mAb) showing great potential for use either for therapeutic purposes or as a basis of vaccine development, but its antigenic epitope and neutralization mechanism have not been finely characterized. In this study, we first demonstrated that AVFluIgG01 targets a novel conformation-dependent epitope in the globular head region of H5N1 hemagglutinin (HA). By selecting mimotopes from a random peptide library in combination with computational algorithms and site-directed mutagenesis, the epitope was mapped to three conserved discontinuous sites (I-III) that are located closely at the three-dimensional structure of HA. Further, we found that this HA1-specific human mAb can efficiently block both virus-receptor binding and post-attachment steps, while its Fab fragment exerts the post-attachment inhibition only. Consistently, AVFluIgG01 could inhibit HA-mediated cell-cell membrane fusion at a dose-dependent manner and block the acquisition of pH-induced protease sensitivity. These results suggest a neutralization mechanism of AVFluIgG01 by simultaneously blocking viral attachment to the receptors on host cells and interfering with HA conformational rearrangements associated with membrane fusion. The presented data provide critical information for developing novel antiviral therapeutics and vaccines against HPAI H5N1 virus

Single Cell Clonotypic and Transcriptional Evolution of Multiple Myeloma Precursor Disease

Multiple myeloma remains an incurable disease, and the cellular and molecular evolution from precursor conditions, including monoclonal gammopathy of undetermined significance and smoldering multiple myeloma, is incompletely understood. Here, we combine single-cell RNA and B cell receptor sequencing from fifty-two patients with myeloma precursors in comparison with myeloma and normal donors. Our comprehensive analysis reveals early genomic drivers of malignant transformation, distinct transcriptional features, and divergent clonal expansion in hyperdiploid versus non-hyperdiploid samples. Additionally, we observe intra-patient heterogeneity with potential therapeutic implications and identify distinct patterns of evolution from myeloma precursor disease to myeloma. We also demonstrate distinctive characteristics of the microenvironment associated with specific genomic changes in myeloma cells. These findings add to our knowledge about myeloma precursor disease progression, providing valuable insights into patient risk stratification, biomarker discovery, and possible clinical applications