Isotropic Representation Can Improve Dense Retrieval

The recent advancement in language representation modeling has broadly affected the design of dense retrieval models. In particular, many of the high-performing dense retrieval models evaluate representations of query and document using BERT, and subsequently apply a cosine-similarity based scoring to determine the relevance. BERT representations, however, are known to follow an anisotropic distribution of a narrow cone shape and such an anisotropic distribution can be undesirable for the cosine-similarity based scoring. In this work, we first show that BERT-based DR also follows an anisotropic distribution. To cope with the problem, we introduce unsupervised post-processing methods of Normalizing Flow and whitening, and develop token-wise method in addition to the sequence-wise method for applying the post-processing methods to the representations of dense retrieval models. We show that the proposed methods can effectively enhance the representations to be isotropic, then we perform experiments with ColBERT and RepBERT to show that the performance (NDCG at 10) of document re-ranking can be improved by 5.17\%$\sim$8.09\% for ColBERT and 6.88\%$\sim$22.81\% for RepBERT. To examine the potential of isotropic representation for improving the robustness of DR models, we investigate out-of-distribution tasks where the test dataset differs from the training dataset. The results show that isotropic representation can achieve a generally improved performance. For instance, when training dataset is MS-MARCO and test dataset is Robust04, isotropy post-processing can improve the baseline performance by up to 24.98\%. Furthermore, we show that an isotropic model trained with an out-of-distribution dataset can even outperform a baseline model trained with the in-distribution dataset.Comment: 9 pages, 4 figure

Colonic Spirochetosis in a 60-Year-Old Immunocompetent Patient: Case Report and Review

Spirochetes, a genetically and morphologically distinct group of bacteria, are thin, spiral-shaped, and highly motile. They are known causes of several human diseases such as syphilis, Lyme disease, relapsing fever, and leptospirosis. We report a case of colonic spirochetosis in a healthy patient presenting for surveillance colonoscopy. The diagnosis of intestinal spirochetosis was made accidentally during the histological examination of colonic polyps, which were removed during colonoscopy. We also performed an extensive review on intestinal spirochetosis with a focus on clinical presentation and outcomes of reported cases from the past two decades

Percutaneous Biopsy of the Renal Mass: Fine Needle Aspiration or Core Biopsy?

BACKGROUND In recent years, there have been increasing indications for percutaneous renal biopsy. Fine-needle aspiration (FNA), with or without core needle biopsy (CB), has been used increasingly in the management of renal tumors at the study institution. METHODS A computerized search of laboratory records was conducted to retrieve FNA cases of renal masses as well as the correlating CB and/or nephrectomy specimens. The cases spanned a period of 10 years (2006-2015). The diagnoses were classified into 5 categories: malignant, suspicious for malignancy, neoplastic, atypical, and negative/nondiagnostic. Based on the results of the nephrectomy specimens, the diagnostic rate, sensitivity, and diagnostic accuracy were calculated among 3 groups of specimens: FNA only, CB only, and combined FNA and CB. RESULTS A total of 247 cases of FNA with 123 correlating CB and 101 follow-up nephrectomy specimens were identified. The diagnostic rate, sensitivity, and diagnostic accuracy were 72%, 78%, and 96%, respectively, for FNA; 87%, 92%, and 94%, respectively, for CB; and 92%, 92%, and 94%, respectively, for the combined FNA and CB group. Renal cell carcinoma and its variants were the most common histologic diagnoses (112 of 174 cases; 64%). Significant diagnostic discrepancy was noted in one case: a malignant melanoma that was misdiagnosed as renal cell carcinoma in both the preoperative FNA specimen and in the CB specimen. CONCLUSIONS In the current study, both FNA and CB demonstrated excellent diagnostic accuracy (96% and 94%, respectively). The combination of FNA and CB was found to significantly improve the diagnostic rate when compared with either FNA alone (92% vs 72%; P<.05) or CB alone (92% vs 87%)

Chromosome-level genome assembly of Patagonian moray cod (Muraenolepis orangiensis) and immune deficiency of major histocompatibility complex (MHC) class II

The Patagonian moray cod, Muraenolepis orangiensis, belongs to the family Muraenolepididae and is the sole order of Gadiformes that inhabits the temperate and cold waters of the southern hemisphere. One of the features of the Gadiformes order is that they have a remarkably unique immune gene repertoire that influences innate and adaptive immunity, and they lack major histocompatibility complex (MHC) class II, invariant chains (CD74), and CD4 genes. In this study, a high-quality chromosome-level genome assembly was constructed, resulting in a final assembled genome of 893.75 Mb, with an N50 scaffold length of 30.07 Mb and the longest scaffold being 39.77 Mb. Twenty-five high-quality pseudochromosomes were assembled, and the complete BUSCO rate was 93.4%. A total of 34,553 genes were structurally annotated, and 27,691 genes were functionally annotated. Among the 10 primary genes involved in MHC class II, only two ERAP1 genes and one AIRE gene were identified through the genome study. Although no specific reason for the MHC class II deficiency has been identified, it has been shown that the toll-like receptors (TLRs), which are significant to the innate immune response, are significantly expanded in M. orangiensis. A total of 44 TLRs have been identified, with 32 TLR13 genes distributed evenly on six different pseudochromosomes. This study is the first to reveal the whole genome of a Muraenolepididae family and provides valuable insights into the potential rationale for the MHC class II deficiency in a Gadiformes fish species

Dose response relationship of cumulative anticholinergic exposure with incident dementia: validation study of Korean anticholinergic burden scale

Abstract Background The dose response relationship of nine-year cumulative anticholinergic exposure and dementia onset was investigated using the Korean version anticholinergic burden scale (KABS) in comparison with the Anticholinergic Cognitive Burden Scale (ACB). We also examined the effect of weak anticholinergics in the prediction of dementia. Methods A retrospective case-control study was conducted comprising 86,576 patients after 1:2 propensity score matching using the longitudinal national claims database. For cumulative anticholinergic burden estimation, average daily anticholinergic burden score during the 9 years prior to dementia onset was calculated using KABS and ACB and categorized as minimal, < 0.25; low, 0.25–1; intermediate, 1–2; and high, ≥ 2. Adjusted odds ratio (aOR) between cumulative anticholinergic burden and incident dementia was estimated. Results Patients with high exposure according to KABS and ACB comprised 3.2 and 3.4% of the dementia cohort and 2.1 and 2.8% of the non-dementia cohort, respectively. Dose-response relationships were observed between anticholinergic burden and incident dementia. After adjusting covariates, compared with minimal exposure, patients with high exposure according to KABS and ACB had a significantly higher risk for incident dementia with aOR of 1.71 (95% confidence interval (CI) 1.55–1.87) and 1.22 (CI 1.12–1.33), respectively. With the exclusion of weak anticholinergics, the association became stronger, i.e., 1.41 (CI 1.14–1.75) with ACB whereas the association became slightly weaker with KABS, i.e., 1.60 (CI 1.38–1.86). Conclusion This study confirmed the dose response relationship for cumulative anticholinergic burden measured using the Korean specific anticholinergic burden scale with incident dementia

Establishment of Efficacy and Safety Assessment of Human Adipose Tissue-Derived Mesenchymal Stem Cells (hATMSCs) in a Nude Rat Femoral Segmental Defect Model

Human adipose tissue-derived mesenchymal stem cell (hATMSC) have emerged as a potentially powerful tool for bone repair, but an appropriate evaluation system has not been established. The purpose of this study was to establish a preclinical assessment system to evaluate the efficacy and safety of cell therapies in a nude rat bone defect model. Segmental defects (5 mm) were created in the femoral diaphyses and transplanted with cell media (control), hydroxyapatite/tricalcium phosphate scaffolds (HA/TCP, Group I), hATMSCs (Group II), or three cell-loading density of hATMSC-loaded HA/TCP (Group III-V). Healing response was evaluated by serial radiography, micro-computed tomography and histology at 16 weeks. To address safety-concerns, we conducted a GLP-compliant toxicity study. Scanning electron microscopy studies showed that hATMSCs filled the pores/surfaces of scaffolds in a cell-loading density-dependent manner. We detected significant increases in bone formation in the hATMSC-loaded HA/TCP groups compared with other groups. The amount of new bone formation increased with increases in loaded cell number. In a toxicity study, no significant hATMSC-related changes were found in body weights, clinical signs, hematological/biochemical values, organ weights, or histopathological findings. In conclusion, hATMSCs loaded on HA/TCP enhance the repair of bone defects and was found to be safe under our preclinical efficacy/safety hybrid assessment system

Systematic reconstruction of TRANSPATH data into Cell System Markup Language

<p>Abstract</p> <p>Background</p> <p>Many biological repositories store information based on experimental study of the biological processes within a cell, such as protein-protein interactions, metabolic pathways, signal transduction pathways, or regulations of transcription factors and miRNA. Unfortunately, it is difficult to directly use such information when generating simulation-based models. Thus, modeling rules for encoding biological knowledge into system-dynamics-oriented standardized formats would be very useful for fully understanding cellular dynamics at the system level.</p> <p>Results</p> <p>We selected the TRANSPATH database, a manually curated high-quality pathway database, which provides a plentiful source of cellular events in humans, mice, and rats, collected from over 31,500 publications. In this work, we have developed 16 modeling rules based on hybrid functional Petri net with extension (HFPNe), which is suitable for graphical representing and simulating biological processes. In the modeling rules, each Petri net element is incorporated with Cell System Ontology to enable semantic interoperability of models. As a formal ontology for biological pathway modeling with dynamics, CSO also defines biological terminology and corresponding icons. By combining HFPNe with the CSO features, it is possible to make TRANSPATH data to simulation-based and semantically valid models. The results are encoded into a biological pathway format, Cell System Markup Language (CSML), which eases the exchange and integration of biological data and models.</p> <p>Conclusion</p> <p>By using the 16 modeling rules, 97% of the reactions in TRANSPATH are converted into simulation-based models represented in CSML. This reconstruction demonstrates that it is possible to use our rules to generate quantitative models from static pathway descriptions.</p

Biofilm and Cancer: Interactions and Future Directions for Cancer Therapy

There is a growing body of evidence supporting the significant role of bacterial biofilms in the pathogenesis of various human diseases, including cancer. Biofilms are polymicrobial communities enclosed within an extracellular matrix composed of polysaccharides, proteins, extracellular DNA, and lipids. This complex matrix provides protection against antibiotics and host immune responses, enabling the microorganisms to establish persistent infections. Moreover, biofilms induce anti-inflammatory responses and metabolic changes in the host, further facilitating their survival. Many of these changes are comparable to those observed in cancer cells. This review will cover recent research on the role of bacterial biofilms in carcinogenesis, especially in colorectal (CRC) and gastric cancers, emphasizing the shared physical and chemical characteristics of biofilms and cancer. This review will also discuss the interactions between bacteria and the tumor microenvironment, which can facilitate oncogene expression and cancer progression. This information will provide insight into developing new therapies to identify and treat biofilm-associated cancers, such as utilizing bacteria as delivery vectors, using bacteria to upregulate immune function, or more selectively targeting biofilms and cancer for their shared traits