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Teleost fish have evolved various adaptations that allow them to tolerate cold water conditions. However, the underlying mechanism of this adaptation is poorly understood in Tibetan Plateau fish. RNA-seq combined with liquid chromatography‒mass spectrometry (LC‒MS/MS) metabolomics was used to investigate the physiological responses of a Tibetan Plateau-specific teleost, Gymnocypris przewalskii, under cold conditions. The 8-month G. przewalskii juvenile fish were exposed to cold (4 ℃, cold acclimation, CA) and warm (17 ℃, normal temperature, NT) temperature water for 15 days. Then, the transcript profiles of eight tissues, including the brain, gill, heart, intestine, hepatopancreas, kidney, muscle, and skin, were evaluated by transcriptome sequencing. The metabolites of the intestine, hepatopancreas, and muscle were identified by LC‒MS/MS. A total of 5,745 differentially expressed genes (DEGs) were obtained in the CA group. The key DEGs were annotated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The DEGs from the eight tissues were significantly enriched in spliceosome pathways, indicating that activated alternative splicing is a critical biological process that occurs in the tissues to help fish cope with cold stress. Additionally, 82, 97, and 66 differentially expressed metabolites were identified in the intestine, hepatopancreas, and muscle, respectively. Glutathione metabolism was the only overlapping significant pathway between the transcriptome and metabolome analyses in these three tissues, indicating that an activated antioxidative process was triggered during cold stress. In combination with the multitissue transcriptome and metabolome, we established a physiology-gene‒metabolite interaction network related to energy metabolism during cold stress and found that gluconeogenesis and long-chain fatty acid metabolism played critical roles in glucose homeostasis and energy supply. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate changes in systemic and local immune factors, namely, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, in patients with and without osteoporotic fractures and to explore the effects of active vitamin D3 treatment on immune function and fracture prognosis in patients with osteoporotic fractures. Method: The mRNA expression levels of IL-1β, IL-6 and TNF-α were measured before the operation. After the operation, the patients in the control group were treated with conventional fracture treatment and calcium supplementation, and the patients in the treatment group were treated with calcium plus active vitamin D3 in addition to conventional fracture treatment. The serum of each patient was collected on the seventh day after the operation. Results: The expression levels of the three immune factors (IL-1β, IL-6 and TNF-α) in the fracture end hematoma samples were significantly positively correlated with those in the serum samples (P < 0.05). The mean values of the serums of IL-1β, IL-6 and TNF-α in the osteoporosis group were significantly higher than those in the non-osteoporosis group (P < 0.05). The average number of hematomas in the osteoporosis group was significantly higher than that in the non-osteoporosis group (P < 0.05). The results for the active vitamin D3 treatment group were significantly lower than those for the control group (P < 0.05). The mean wrist function score of the active vitamin D3 treatment group was significantly better than that of the control group (P < 0.05). The average fracture healing time of the treatment group was significantly shorter than that of the control group (P < 0.05). Conclusion: The relative expression of IL-1β, IL-6, and TNF-α in the fracture end hematoma samples was positively correlated with the corresponding levels of these immune factors in the serum samples. The levels of IL-1β, IL-6 and TNF-α in the serum and fracture end hematoma samples of the osteoporotic fracture patients were higher than those of the non-osteoporotic fracture patients. Active vitamin D3 treatment promoted fracture healing by affecting the levels of these immune factors. [ABSTRACT FROM AUTHOR]

Background: The Tibetan highland fish, Gymnocypris przewalskii, migrates from Lake Qinghai to its spawning grounds every summer. This seasonal reproduction is critically regulated by intrinsic and extrinsic signals. However, the molecular mechanisms that process environmental oscillations to initiate the seasonal mating are largely unknown. Results: A transcriptomic analysis was conducted on the brain and gonad of male and female G. przewalskii in reproductive and nonreproductive seasons. We obtained 2034, 760, 1158 and 17,856 differentially expressed genes between the reproductively active and dormant female brain, male brain, ovary and testis. Among these genes, DIO2 was upregulated in the reproductively active brain and gonad of both males and females. Neuroactive ligand-receptor genes were activated in male and female brain. Functional enrichment analysis suggested that retinol metabolism was uniquely stimulated in reproductively active males. Genes involved in GnRH signaling and sex hormone synthesis exhibited higher expression levels in brain and gonad during the reproductive season. A co-expression network classified all the genes into 9 modules. The network pinpointed CDC42 as the hub gene that connected the pathways in responsible for modulating reproduction in G. przewalskii. Meanwhile, the sex pheromone receptor gene prostaglandin receptor was identified to link to multiple endocrine receptors, such as GnRHR2 in the network. Conclusions: The current study profiled transcriptomic variations between reproductively active and dormant fish, highlighting the potential regulatory mechanisms of seasonal reproduction in G. przewalskii. Our data suggested that the seasonal regulation of reproduction in G. przewalskii was controlled by the external stimulation of photoperiodic variations. The activated transcription of neuroendocrine and sex hormone synthesis genes contributed to seasonal reproduction regulation in G. przewalskii, which was presumably influenced by the increased day-length during the breeding season. [ABSTRACT FROM AUTHOR]

The wide adoption of electronic health records (EHRs) has led to an improvement in healthcare quality by electronically documenting a patient's medical conditions, thoughts and actions among the care providers [[1]]. Towards this goal, we organized the BioCreative/OHNLP Challenge 2018 workshop (https://sites.google.com/view/ohnlp2018/home) to promote community efforts on methodological advancements and data curation mechanisms in clinical NLP. Therefore, there is a growing need for tools that can aggregate data from diverse sources and minimize data redundancy, and organize and present the EHR data in a user-friendly way to reduce physicians' cognitive burden. [Extracted from the article]

Backgroud: Whole-body vibration(WBV) has been suggested for the prevention of subchondral bone loss of knee osteoarthritis (OA) . This study examined the effects of different frequency of whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation and metabolism of the tibia and femoral condyle bone, and joint pain in an anterior cruciate ligament transection (ACLT)-induced knee osteoarthritisrabbit model.Method: Ninety adult rabbits were divided into six groups: all groups received unilateral ACLT; Group 1, ACLT only; Group 2, 5 Hz WBV; Group 3, 10 Hz WBV; Group 4, 20 Hz WBV; Group 5, 30 Hz WBV; and Group 6, 40 Hz WBV. Pain was tested via weight-bearing asymmetry. Subchondral trabecular bone microarchitecture was examined using in vivo micro-computed tomography. Knee joint cartilage was evaluated by gross morphology, histology, and ECM gene expression level (aggrecan and type II collagen [CTX-II]). Serum bone-specific alkaline phosphatase, N-mid OC, cartilage oligometric protein, CPII, type I collagen, PIIANP, G1/G2 aggrecan levels, and urinary CTX-II were analyzed.Results: After 8 weeks of low-magnitude WBV, the lower frequency (10 Hz and 20 Hz) WBV treatment decreased joint pain and cartilage resorption, accelerated cartilage formation, delayed cartilage degradation especially at the 20 Hz regimen. However, the higher frequencies (30 Hz and 40 Hz) had worse effects, with worse limb function and cartilage volume as well as higher histological scores and cartilage resorption. In contrast, both prevented loss of trabeculae and increased bone turnover. No significant change was observed in the 5 Hz WBV group.Conclusion: Our data demonstrate that the lower frequencies (10 Hz and 20 Hz) of low-magnitude WBV increased bone turnover, delayed cartilage degeneration, and caused a significant functional change of the OA-affected limb in ACLT-induced OA rabbit model but did not reverse OA progression after 8 weeks of treatment. [ABSTRACT FROM AUTHOR]

Background: The atherogenic index of plasma (AIP) and cardiovascular disease (CVD) in participants with abnormal glucose metabolism have been linked in previous studies. However, it was unclear whether AIP control level affects the further CVD incidence among with diabetes and pre-diabetes. Therefore, our study aimed to investigate the association between AIP control level with risk of CVD in individuals with abnormal glucose metabolism. Methods: Participants with abnormal glucose metabolism were included from the China Health and Retirement Longitudinal Study. CVD was defined as self-reporting heart disease and/or stroke. Using k-means clustering analysis, AIP control level, which was the log-transformed ratio of triglyceride to high-density lipoprotein cholesterol in molar concentration, was divided into five classes. The association between AIP control level and incident CVD among individuals with abnormal glucose metabolism was investigated multivariable logistic regression analysis and application of restricted cubic spline analysis. Results: 398 (14.97%) of 2,659 participants eventually progressed to CVD within 3 years. After adjusting for various confounding factors, comparing to class 1 with the best control of the AIP, the OR for class 2 with good control was 1.31 (95% CI, 0.90–1.90), the OR for class 3 with moderate control was 1.38 (95% CI, 0.99–1.93), the OR for class 4 with worse control was 1.46 (95% CI, 1.01–2.10), and the OR for class 5 with consistently high levels was 1.56 (95% CI, 1.03–2.37). In restricted cubic spline regression, the relationship between cumulative AIP index and CVD is linear. Further subgroup analysis demonstrated that the similar results were observed in the individuals with agricultural Hukou, history of smoking, diastolic blood pressure ≥ 80mmHg, and normal body mass index. In addition, there was no interaction between the AIP control level and the subgroup variables. Conclusions: In middle-aged and elderly participants with abnormal glucose metabolism, constant higher AIP with worst control may have a higher incidence of CVD. Monitoring long-term AIP change will contribute to early identification of high risk of CVD among individuals with abnormal glucose metabolism. [ABSTRACT FROM AUTHOR]

Endometrioid carcinoma with sex cord-like formations and hyalinization of the uterine corpus, or corded and hyalinized endometrioid adenocarcinoma (CHEC), is a rare morphological variant of endometrioid carcinoma, for which there is limited literature and few cases reports. Most researchers tend to consider CHEC as a low-grade cancer with a favorable prognosis. Full-staging surgery is the primary choice for this disease, and no case of CHEC has been previously reported to be treated conservatively. Here, we present the following case to explore the possibility of fertility-preserving treatment for young women with CHEC. A 23-year-old nulliparous patient diagnosed with presumed stage IA CHEC received fertility-sparing treatment at the Obstetrics and Gynecology Hospital of Fudan University and got a complete response (CR) after 10 months of conservative treatment. The patient subsequently became pregnant spontaneously, successfully conceived, and gave birth to a healthy male neonate without any sign of recurrence during 37 months follow-up after CR. The patient's postpartum follow-up is continuing. Presently, CHEC is not included in the fertility-sparing field of any available guidelines. This case indicates that fertility-sparing treatment may be an option for highly selected patients with CHEC. Continuous follow-up remains mandatory to observe long-term outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of fertility-preserving treatment for young women with synchronous primary neoplasm of endometrium and ovary. Methods: We retrospectively reviewed eight patients with concurrent primary grade 1 presumed stage IA endometrioid endometrial adenocarcinoma (EEA) or endometrial atypical hyperplasia (EAH) and primary stage I ovarian tumors who underwent fertility-sparing treatment in the Obstetrics and Gynecology Hospital of Fudan University between April 2016 and December 2022. Results: Synchronous endometrial and ovarian cancers (SEOC) accounted for 50% of these eight patients. The median age of patients was 30.5 years (range, 28–34 years). None of them received chemotherapy. The median treatment time was 4 months (range, 3–8 months). 87.5% (7/8) cases achieved complete response (CR), and the median time to CR was 3.8 months (range, 1.5–7.7 months). Among patients who got CR, none of them showed any signs of recurrence. Pregnancies and successful deliveries were achieved in 4 of 5 patients. Till September 2023, the median follow-up period was 50.5 months (range:15.2–85.2 months). Conclusion: Fertility-sparing treatment is feasible for highly selected patients with synchronous neoplasm of the endometrium and ovary, but strict screening and monitoring are mandatory. Though the results of our limited cases are encouraging, long follow-up and more clinical data are required. Enrolled patients must be fully informed of the risks during conservative treatment. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) remains one of the most serious infectious diseases worldwide. China has the second highest TB burden globally, but existing studies have mostly neglected the post-tuberculosis (post-TB) disease burden. This study estimated the disease burden of TB and post-TB in Inner Mongolia, China, from 2016 to 2018. Methods: Population data were collected from TB Information Management System. Post-TB disease burden was defined as the burden caused by Chronic Obstructive Pulmonary Disease (COPD) occurring after patients with TB were cured. To estimate the incidence rate of TB, standardized mortality rate, life expectancy, and cause eliminated life expectancy, using descriptive epidemiological, abridged life table and cause eliminated life table. On this basis, the Disability-Adjusted Life Years (DALY), Years Lived with Disability (YLD) and Years of Life Lost (YLL) due to TB were further be estimated. The data were analyzed using Excel 2016 and SPSS 26.0. Joinpoint regression models were used to estimate the time and age trends of the disease burden of TB and post-TB. Results: The TB incidence in 2016, 2017, and 2018 was 41.65, 44.30, and 55.63/100,000, respectively. The standardized mortality in the same period was 0.58, 0.65, and 1.08/100,000, respectively. From 2016 to 2018, the total DALYs of TB and post-TB were 5923.33, 6258.03, and 8194.38 person-years, and the DALYs of post-TB from 2016 to 2018 were 1555.89, 1663.33, and 2042.43 person-years. Joinpoint regression showed that the DALYs rate increased yearly from 2016 to 2018, and the rate of males was higher than that of females. TB and post-TB DALYs rates showed a rising tendency with increasing age (AAPC values were 149.6% and 157.0%, respectively, P < 0.05), which was higher in the working-age population and elderly. Conclusion: The disease burden of TB and post-TB was heavy and increased year by year in Inner Mongolia from 2016 to 2018. Compared with the youngster and females, working-age population and the elderly and males had a higher disease burden. Policymakers should be paid more attention to the patients' sustained lung injury after TB cured. There is a pressing need to identify more effective measures for reducing the burden of TB and post-TB of people, to improve their health and well-being. [ABSTRACT FROM AUTHOR]

Background: Triplophysa stoliczkae is the most widespread species in the genus Triplophysa and may have originated from morphological convergence. To understand the evolutionary history of T. stoliczkae, we employed a multilocus approach to investigate the phylogenetics and the morphological evolution of T. stoliczkae on the Qinghai-Tibetan Plateau. Results: All phylogenetic analyses (two mitochondrial and five nuclear loci), a genealogical sorting index and species tree inferences suggested that T. stoliczkae consists of distinct lineages that were not closest relatives. The time estimation indicated that the divergence events between "T. stoliczkae" and other Triplophysa species occurred from approximately 0.10 to 4.51 Ma. The ancestral state analyses supported the independent evolution of T. stoliczkae morphology in distinct lineages. The morphometric analysis and convergence estimates demonstrated significant phenotypic convergence among "T. stoliczkae" lineages. Conclusions: Triplophysa stoliczkae includes 4 different lineages with similar morphologies. The increasingly harsh environments that have occurred since the Pliocene have driven the occurrences of scrape-feeding fish in the genus Triplophysa. Morphological adaptations associated with scrape-feeding behavior resulted in convergences and the artificial lumping of four different species in the nominal taxon T. stoliczkae. A taxonomic revision for T. stoliczkae is needed. [ABSTRACT FROM AUTHOR]

Background: Automatic clinical text classification is a natural language processing (NLP) technology that unlocks information embedded in clinical narratives. Machine learning approaches have been shown to be effective for clinical text classification tasks. However, a successful machine learning model usually requires extensive human efforts to create labeled training data and conduct feature engineering. In this study, we propose a clinical text classification paradigm using weak supervision and deep representation to reduce these human efforts.Methods: We develop a rule-based NLP algorithm to automatically generate labels for the training data, and then use the pre-trained word embeddings as deep representation features for training machine learning models. Since machine learning is trained on labels generated by the automatic NLP algorithm, this training process is called weak supervision. We evaluat the paradigm effectiveness on two institutional case studies at Mayo Clinic: smoking status classification and proximal femur (hip) fracture classification, and one case study using a public dataset: the i2b2 2006 smoking status classification shared task. We test four widely used machine learning models, namely, Support Vector Machine (SVM), Random Forest (RF), Multilayer Perceptron Neural Networks (MLPNN), and Convolutional Neural Networks (CNN), using this paradigm. Precision, recall, and F1 score are used as metrics to evaluate performance.Results: CNN achieves the best performance in both institutional tasks (F1 score: 0.92 for Mayo Clinic smoking status classification and 0.97 for fracture classification). We show that word embeddings significantly outperform tf-idf and topic modeling features in the paradigm, and that CNN captures additional patterns from the weak supervision compared to the rule-based NLP algorithms. We also observe two drawbacks of the proposed paradigm that CNN is more sensitive to the size of training data, and that the proposed paradigm might not be effective for complex multiclass classification tasks.Conclusion: The proposed clinical text classification paradigm could reduce human efforts of labeled training data creation and feature engineering for applying machine learning to clinical text classification by leveraging weak supervision and deep representation. The experimental experiments have validated the effectiveness of paradigm by two institutional and one shared clinical text classification tasks. [ABSTRACT FROM AUTHOR]

Background: Existing resources to assist the diagnosis of rare diseases are usually curated from the literature that can be limited for clinical use. It often takes substantial effort before the suspicion of a rare disease is even raised to utilize those resources. The primary goal of this study was to apply a data-driven approach to enrich existing rare disease resources by mining phenotype-disease associations from electronic medical record (EMR).Methods: We first applied association rule mining algorithms on EMR to extract significant phenotype-disease associations and enriched existing rare disease resources (Human Phenotype Ontology and Orphanet (HPO-Orphanet)). We generated phenotype-disease bipartite graphs for HPO-Orphanet, EMR, and enriched knowledge base HPO-Orphanet + and conducted a case study on Hodgkin lymphoma to compare performance on differential diagnosis among these three graphs.Results: We used disease-disease similarity generated by the eRAM, an existing rare disease encyclopedia, as a gold standard to compare the three graphs with sensitivity and specificity as (0.17, 0.36, 0.46) and (0.52, 0.47, 0.51) for three graphs respectively. We also compared the top 15 diseases generated by the HPO-Orphanet + graph with eRAM and another clinical diagnostic tool, the Phenomizer.Conclusions: Per our evaluation results, our approach was able to enrich existing rare disease knowledge resources with phenotype-disease associations from EMR and thus support rare disease differential diagnosis. [ABSTRACT FROM AUTHOR]