Revealing the pathogenesis of gastric intestinal metaplasia based on the mucosoid air-liquid interface

Background: Gastric intestinal metaplasia (GIM) is an essential precancerous lesion. Although the reversal of GIM is challenging, it potentially brings a state-to-art strategy for gastric cancer therapeutics (GC). The lack of the appropriate in vitro model limits studies of GIM pathogenesis, which is the issue this work aims to address for further studies. Method: The air-liquid interface (ALI) model was adopted for the long-term culture of GIM cells in the present work. This study conducted Immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR), transcriptomic sequencing, and mucoproteomic sequencing (MS) techniques to identify the pathways for differential expressed genes (DEGs) enrichment among different groups, furthermore, to verify novel biomarkers of GIM cells. Result: Our study suggests that GIM-ALI model is analog to the innate GIM cells, which thus can be used for mucus collection and drug screening. We found genes MUC17, CDA, TRIM15, TBX3, FLVCR2, ONECUT2, ACY3, NMUR2, and MAL2 were highly expressed in GIM cells, while GLDN, SLC5A5, MAL, and MALAT1 showed down-regulated, which can be used as potential biomarkers for GIM cells. In parallel, these genes that highly expressed in GIM samples were mainly involved in cancer-related pathways, such as the MAPK signal pathway and oxidative phosphorylation signal pathway. Conclusion: The ALI model is validated for the first time for the in vitro study of GIM. GIM-ALI model is a novel in vitro model that can mimic the tissue micro-environment in GIM patients and further provide an avenue for studying the characteristics of GIM mucus. Our study identified new markers of GIM as well as pathways associated with GIM, which provides outstanding insight for exploring GIM pathogenesis and potentially other related conditions

Hypophyseal Involvement in Immunoglobulin G4-Related Disease: A Retrospective Study from a Single Tertiary Center

This study aims to outline the clinical features and outcomes of IgG4-related hypophysitis (IgG4-RH) patients in a tertiary medical center. We reviewed clinical manifestations and imaging and pituitary function tests at baseline, as well as during follow-up. Ten patients were included. The mean age at diagnosis of IgG4-RH was 48.4 (16.0–64.0) years. An average of 3 (0–9) extrapituitary organs were involved. Five patients had panhypopituitarism, three had only posterior hypopituitarism, one had only anterior hypopituitarism, and one had a normal pituitary function. One patient in our study had pituitary mass biopsy, lacking IgG4-positive cells despite lymphocyte infiltration forming an inflammatory pseudotumor. Five patients with a clinical course of IgG4-RH less than nine months and a whole course of IgG4-RD less than two years were managed with glucocorticoids, while three patients with a longer history were administered glucocorticoids plus immunosuppressive agents. One patient went through surgical excision, and one patient was lost to follow-up. All patients showed a prompt response clinically, but only three patients had normalized serum IgG4 levels. Two patients who took medications for less than six months relapsed. Conclusions. IgG4-RD is a broad disease, and all physicians involved have to be aware of the possibility of pituitary dysfunction. Younger patients should be expected. The histopathological feature of pituitary gland biopsy could be atypical. For patients with a longer history, the combination of GC and immunosuppressive agents is favorable. Early and adequate courses of treatment are crucial for the management of IgG4-RH. With GC and/or immunosuppressant treatment, however, pituitary function or diabetes insipidus did not improve considerably

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Are Pay Decisions Based on Pre-Contract Efficiency Necessarily Correct? Evidence From Players Contracts of National Basketball Association

This article explores whether pay decisions based on pre-contract efficiency are necessarily correct. Overcoming methodology problems of previous studies, we use each player’s contract of National Basketball Association (NBA) as an observation. The empirical results show that managers indeed pay their employees according to an evaluation of their pre-contract efficiency. However, the pay decisions are not correct. Relative to the final year of the last contract, employees’ efficiency in the first year of the current contract decreases with increased salary. The reason is that managers put more weight on players’ efficiency in the final year of the last contract than on the average efficiency. Our findings deepen our understanding of the mechanism of compensation contract

GLS: New class of generalized Legendre sequences with optimal arithmetic cross-correlation

The Legendre symbol has been used to construct sequences with ideal cross-correlation, but it was never used in the arithmetic cross-correlation. In this paper, a new class of generalized Legendre sequences are described and analyzed with respect to their period, distributional, arithmetic cross-correlation and distinctness properties. This analysis gives a new approach to study the connection between the Legendre symbol and the arithmetic cross-correlation. In the end of this paper, possible application of these sequences with optimal arithmetic cross-correlation is indicated

Morphologic Characters of the Rostrum in Two Weevils, <i>Eucryptorrhynchus scrobiculatus</i> Motschulsky and <i>E. brandti</i> Harold (Coleoptera: Curculionidae: Cryptorrhychinae)

(1) Eucryptorrhynchus scrobiculatus and E. brandti (Coleoptera: Curculionidae: Cryptorrhychinae) are both pests of Ailanthus altissima, found in China. During ovipositing, gravid females of the two weevils need to excavate a cavity in the oviposition substrate with their rostrum, while their oviposition sites are different. (2) In this study, to explore the boring mechanism of E. scrobiculatus and E. brandti during ovipositing, the morphologic characters of the rostra of two weevils were studied in detail by scanning electron microscopy and micro-CT. (3) Their rostra appear similar, but the rostrum surface of E. scrobiculatus is rougher than that of E. brandti; their fine structures of rostrum and sensilla distribution are similar, but the sensilla twig basiconica 3 is distributed at the apex of labial palpus in E. brandti females, while not at the apex of labial palpus in E. scrobiculatus females; their rostra are hollow and their cuticle thickness is constantly changing, but the proportion of the whole rostrum tube cuticle in E. scrobiculatus is significantly larger than that of E. brandti. The above structural differences make E. scrobiculatus more conducive to oviposition in the soil and E. brandti more conducive to oviposition in the trunk of A. altissima. (4) Overall, this study not only plays an important role in exploring the excavating mechanism during the oviposition of the two weevils, but also provides new insights into the coexistence of two weevil species on the same host A. altissima