PO-049 The Effects of Altitude Training on Erythropoietic Response and Hematological Variables in elite endurance athletes

Objective To increase the capacity of blood oxygen-carrying of the endurance performance in athletes is the goal of altitude training. The key factor in the achievement of enhanced hematological variables is the stimulation in the hypoxia condition. Reticulocyte celles is the earliest red blood cells released to the bloods, it to be matured about 4days in the marrow. There are lots of research in the clinic tested reticulocyte can be monitor the change of the bone marrow hematopoietic system. The purpose of this study was to find out the effect of altitude training on reticulocyte indices of elite endurance athletes, further to analyzes the kinetics of erythropoiesis and hematological variables during and after altitude training. Methods  The main content of high altitude training are as following: 1~2weeks before the plateau, the main content of training was special aerobic endurance training and special strength endurance training; 1~5days after plateau, the main content of training was Low intensity, relaxation of the adaptive training; 5~15day after plateau, the main content of training was Intensive training phase, the main content of training was aerobic endurance and greater intensity of the special training; 16~20 days after the plateau, adjustment training 21~25days after the plateau, the main content of training was same to the training plan of 5~15day after plateau; 2~3days after return to the sea level, adjustment training; 1~2days after return to the sea level, the mainly training content was rhythm and strength training; 2 weeks after return to the sea level, the mainly content of training was normal training, the intensity of training was greater than the intensity in the sea level. At this stage, we tested the changes of the reticulocyte indices before \after half past three weeks altitude（2366m,DuoBa,QingHai）training, to provided the basis for the develop research the influence of the bone marrow hematopoietic system. Blood parameters were collected two days before altitude training\two days after off altitude\ two weeks after altitude. All the data measured from venous blood samples (1.5~2ml) collected via venipuncture from athletes in a supine position. All the samples were tested using ADVIA120. Data were analyzed by spss17.0 software. Results MCVr/RDWr were significantly increased after altitude training, P＜0.05; CHCMr and RDWr significantly decreased after altitude training, P＜0.05; CHCMr were changed more significantly between before and after , P＜0.01; the reason why retici# was decreased were analyzed that when the athletes training in the hypoxia condition, lack of oxygen and the mechanical injury of friction resulting in a new generation of reticulocyte number was less than the number of destruction. Hb\#RETIC\RDW were changed significantly, P＜0.05; but there was no significant changed find in RBC/HCT. After two weeks off altitude, MCVr、CHCMr、#RETIC、%RETIC all had significantly changed，P＜0.05;and #RETIC，P＜0.01；Hb is significantly increased controlled to the indices which tested before the athletes went to the altitude. It indicated altitude training can stimulated the bone marrow hematopoietic system to released more reticulocyte cells.RBC and HCT were decreased in our study ,but they were not showed any  significantly changed, to analyzed that we found it was relatively large individual differences, which mean the athletes had the different reaction when they training in the plateau and after they back to the sea level; RDW was increased ,but it was not showed the significantly changes too. IRF was increased, but #RETIC\%RETIC\RBCwere decreased after back to the sea level, it showed that the #reticulocyte was not increased, it means that the consumption of the RBC was faster than the number of the erythropoiesis. The indices(CHr、MCVr、CHCMr) which correlated with the Hb contents was increased significantly, it indicated the stimulate of the hypoxia condition can enhance the synthetic of hemoglobin content, but the effect was not occur immediately, it will occurred after 2~3weeks after the athletes back to the sea level. Conclusions Because the test groups were top-level middle-long distance race athletes, they were adapt the training stimulate, so it can not make the reticulocyte indices changed solely, but in the plateau where lack of the oxygen, it will be result the bone marrow hematopoietic system to released more reticulocyte cells to satisfied the needs of the oxygen; the indices which be mutually related with Hb and #reticulocyte both showed the good effece, it indicated that there had certain effect of altitude training on erythropoiesis, but these changes did not showed immediately, it needs 2~3 weeks to occur after returning to sea level

Histone demethylase PHF8 drives neuroendocrine prostate cancer progression by epigenetically upregulating FOXA2.

Neuroendocrine prostate cancer (NEPC) is a more aggressive subtype of castration-resistant prostate cancer (CRPC). Although it is well established that PHF8 can enhance prostate cancer cell proliferation, whether PHF8 is involved in prostate cancer initiation and progression is relatively unclear. By comparing the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without Phf8 knockout, we systemically examined the role of PHF8 in prostate cancer development. We found that PHF8 plays a minimum role in initiation and progression of adenocarcinoma. However, PHF8 is essential for NEPC because not only is PHF8 highly expressed in NEPC but also animals without Phf8 failed to develop NEPC. Mechanistically, PHF8 transcriptionally upregulates FOXA2 by demethylating and removing the repressive histone markers on the promoter region of the FOXA2 gene, and the upregulated FOXA2 subsequently regulates the expression of genes involved in NEPC development. Since both PHF8 and FOXA2 are highly expressed in NEPC tissues from patients or patient-derived xenografts, the levels of PHF8 and FOXA2 can either individually or in combination serve as NEPC biomarkers and targeting either PHF8 or FOXA2 could be potential therapeutic strategies for NEPC treatment. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland

DiTing: A large-scale Chinese seismic benchmark dataset for artificial intelligence in seismologyKey points

In recent years, artificial intelligence technology has exhibited great potential in seismic signal recognition, setting off a new wave of research. Vast amounts of high-quality labeled data are required to develop and apply artificial intelligence in seismology research. In this study, based on the 2013–2020 seismic cataloging reports of the China Earthquake Networks Center, we constructed an artificial intelligence seismological training dataset (“DiTing”) with the largest known total time length. Data were recorded using broadband and short-period seismometers. The obtained dataset included 2,734,748 three-component waveform traces from 787,010 regional seismic events, the corresponding P- and S-phase arrival time labels, and 641,025 P-wave first-motion polarity labels. All waveforms were sampled at 50 Hz and cut to a time length of 180 s starting from a random number of seconds before the occurrence of an earthquake. Each three-component waveform contained a considerable amount of descriptive information, such as the epicentral distance, back azimuth, and signal-to-noise ratios. The magnitudes of seismic events, epicentral distance, signal-to-noise ratio of P-wave data, and signal-to-noise ratio of S-wave data ranged from 0 to 7.7, 0 to 330 km, –0.05 to 5.31 dB, and –0.05 to 4.73 dB, respectively. The dataset compiled in this study can serve as a high-quality benchmark for machine learning model development and data-driven seismological research on earthquake detection, seismic phase picking, first-motion polarity determination, earthquake magnitude prediction, early warning systems, and strong ground-motion prediction. Such research will further promote the development and application of artificial intelligence in seismology

FocMech-Flow: Automatic Determination of P-Wave First-Motion Polarity and Focal Mechanism Inversion and Application to the 2021 Yangbi Earthquake Sequence

P-wave first-motion polarity is important for the inversion of earthquake focal mechanism solutions. The focal mechanism solution can further contribute to our understanding of the source rupture process, the fault structure, and the regional stress field characteristics. By using the abundant focal mechanism solutions of small and moderate earthquakes, we can deepen our understanding of fault geometry and the seismogenic environment. In this paper, we propose an automatic workflow, FocMech-Flow (Focal Mechanism-Flow), for identifying P-wave first-motion polarity and focal mechanism inversion with deep learning and applied it to the 2021 Yangbi earthquake sequence. We use a deep learning model named DiTingMotion to detect the P-wave first-motion polarity of 2389 waveforms, resulting in 98.49% accuracy of polarity discrimination compared with human experts. The focal mechanisms of 112 earthquakes are obtained by using the CHNYTX program, which is 3.7 times more than that of the waveform inversion method, and the results are highly consistent. The analysis shows that the focal mechanisms of the foreshock sequence of the Yangbi earthquake are highly consistent and are all of the strike-slip type; the focal mechanisms of the aftershock sequence are complex, mainly the strike-slip type, but there are also reverse and normal fault types. This study shows that the deep learning method has high reliability in determining the P-wave first-motion polarity, and FocMech-Flow can obtain a large number of focal mechanism solutions from small and moderate earthquakes, having promising application in fine-scale stress inversion

Fine Seismogenic Fault Structures and Complex Rupture Characteristics of the 2022 M6.8 Luding, Sichuan Earthquake Sequence Revealed by Deep Learning and Waveform Modeling

Abstract An approximate 236‐year interval in major seismic activity near the southern Xianshuihe fault terminated on 5 September 2022 until a destructive M6.8 Luding earthquake. The strike‐slip mainshock, accompanied by potent normal‐faulting aftershocks, fell short of the previously anticipated M7+ event. Utilizing deep‐learning and source inversion techniques, we analyzed dense near‐field seismograms to examine detailed fault structures and rupture characteristics. Our high‐quality relocated catalog with 7,388 events revealed that the earthquake ruptured an unmapped multiscale fault network. The analysis of the mainshock and 43 ML ≥ 2.8 aftershocks suggests normal‐faulting events relate to the vertical movement of the Gongga Mountain. The sequence length, seismic gaps, and asperities derived from seismicity and waveform modeling imply that the rupture of the M6.8 quake was incomplete, indicating a high risk of a future M6+ event at the northern Moxi segment. These findings hold crucial implications for assessing future seismic hazards in this region

DiTingMotion: A deep-learning first-motion-polarity classifier and its application to focal mechanism inversion

Accurate P-wave first-motion-polarity (FMP) information can contribute to solving earthquake focal mechanisms, especially for small earthquakes, to which waveform-based methods are generally inapplicable due to the computationally expensive high-frequency waveform simulations and inaccurate velocity models. In this paper, we propose a deep-learning-based method for the automatic determination of the FMPs, named “DiTingMotion”. DiTingMotion was trained with the P-wave FMP labels from the “DiTing” and SCSN-FMP datasets, and it achieved ∼97.8% accuracy on both datasets. The model maintains ∼83% accuracy on data labeled as “Emergent”, of which the FMP labels are challenging to identify for seismic analysts. Integrated with HASH, we developed a workflow for automated focal mechanism inversion using the FMPs identified by DiTingMotion and applied it to the 2019 M 6.4 Ridgecrest earthquake sequence for performance evaluation. In this case, DiTingMotion yields comparable focal mechanism results to that using manually determined FMPs by SCSN on the same data. The results proved that the DiTingMotion has a good generalization ability and broad application prospect in rapid earthquake focal mechanism inversion

Primary undifferentiated pleomorphic sarcoma in oral-maxillary area: retrospective study and molecular analysis

y. Undifferentiated pleomorphic sarcoma (UPS) in oral-maxillary area is rarely reported. Herein, we aimed to investigate the clinical characteristics, treatment strategies, prognosis, and molecular features of the oral-maxillary UPS. In total, 10 cases with primary oral-maxillary UPS were included. The rapidly progressive UPS can easily develop to an advanced and life-threatening stage, especially concerning the complex anatomical structures and spaces in the oral-maxillary area. The final diagnosis for UPS greatly depended on histological findings and immunohistochemistry staining after the exclusion of all possible differential diagnoses. Retrospectively, the treatment strategies for the included cases still referred to those of oral squamous cell carcinoma (OSCC). Statistically, the median overall survival (OS) for all the included cases was 7.75 months (range: 5-17 months). Comparatively, 3 cases had improved OS (median survival: 17 months, range: 17-18 months) and experienced PR/SD with neoadjuvant chemotherapy (anlotinib). The molecular features were demonstrated by using whole exonic sequencing for 1 included case. Cancer driver gene detection revealed GBP4 as a candidate driver gene for the primary oralmaxillary UPS. Additionally, a missense mutation in gene PIK3CA (p.E545K) was also identified. Our findings could greatly expand the knowledge about primary oral-maxillary UPS, and provide molecular evidences to improve the therapeutic options for primary oral-maxillary UPS

Comparative analysis of the vaginal bacteriome and virome in healthy women living in high-altitude and sea-level areas

Abstract The vaginal microbiota plays an important role in the health of the female reproductive tract and is closely associated with various pregnancy outcomes and sexually transmitted diseases. Plenty of internal and external factors have strong influence on the changes in a woman's vaginal microbiome. However, the effect of a high-altitude on female vaginal microbiota has not been described. In this study, we characterized the vaginal bacteriome and virome of 13 and 34 healthy women living in high-altitude and sea-level areas, using whole-metagenome shotgun sequencing of their vaginal mucus samples. The results revealed that the vaginal bacteriomes of high-altitude individuals are featured by a significant increase of species diversity, depletion of Lactobacillus crispatus, and more abundant of some anaerobic bacteria, such as Chlamydia trachomatis, Mageeibacillus indolicus, Dialister micraerophilus, and Sneathia amnii). In addition, the vagina samples of sea-level subjects harbor more Lactobacillus strains, whereas the anaerobic bacteroidetes strains mostly appeared in high-altitude subjects. Identified and assembled 191 virus operational taxonomic units (vOTUs), there were significant differences in the abundance of 107 vOTUs between the two groups. Together, the results of this study raised the understanding of bacteriome and virome in the vagina of women at different elevations, and demonstrated that the vaginal microbiome is related to the high-altitude geographic adaptation