Machine learning-based nomogram: integrating MRI radiomics and clinical indicators for prognostic assessment in acute ischemic stroke.

Background: Acute Ischemic Stroke (AIS) remains a leading cause of mortality and disability worldwide. Rapid and precise prognostication of AIS is crucial for optimizing treatment strategies and improving patient outcomes. This study explores the integration of machine learning-derived radiomics signatures from multi-parametric MRI with clinical factors to forecast AIS prognosis. Objective: To develop and validate a nomogram that combines a multi-MRI radiomics signature with clinical factors for predicting the prognosis of AIS. Methods: This retrospective study involved 506 AIS patients from two centers, divided into training (n = 277) and validation (n = 229) cohorts. 4,682 radiomic features were extracted from T1-weighted, T2-weighted, and diffusion-weighted imaging. Logistic regression analysis identified significant clinical risk factors, which, alongside radiomics features, were used to construct a predictive clinical-radiomics nomogram. The model's predictive accuracy was evaluated using calibration and ROC curves, focusing on distinguishing between favorable (mRS ≤ 2) and unfavorable (mRS > 2) outcomes. Results: Key findings highlight coronary heart disease, platelet-to-lymphocyte ratio, uric acid, glucose levels, homocysteine, and radiomics features as independent predictors of AIS outcomes. The clinical-radiomics model achieved a ROC-AUC of 0.940 (95% CI: 0.912-0.969) in the training set and 0.854 (95% CI: 0.781-0.926) in the validation set, underscoring its predictive reliability and clinical utility. Conclusion: The study underscores the efficacy of the clinical-radiomics model in forecasting AIS prognosis, showcasing the pivotal role of artificial intelligence in fostering personalized treatment plans and enhancing patient care. This innovative approach promises to revolutionize AIS management, offering a significant leap toward more individualized and effective healthcare solutions.

Using a Hybrid Multiattribute Decision-Making Model for Evaluating the Sustainable Development Potential of Characteristic Towns and Exploring Development Planning Strategies.

In recent years, with the development of 'China's new urbanization, the "characteristic town movement" with the development of industrial economy first has brought problems to a large number of rural settlements, such as no cultural planning, no consumption of industry, and no soul. Then, in reality, there are still a large number of rural settlements under the planning of the upper-level local government, with the goal of developing into a characteristic town in the future. Therefore, this study believes that there is an urgent need to build a framework for evaluating the construction potential of rural settlements with sustainable characteristic towns. Not only that but also a decision analysis model should be provided for real-world empirical cases. This model needs to cover the assessment of the sustainable development potential of characteristic towns as the goal and the formulation of improvement strategies. This study combines the data collection of current characteristic town development rating reports, applies data exploration technology to extract core impact elements and obtain hierarchical decision rules, integrates expert domain knowledge with DEMATEL technology, and establishes an impact network relationship diagram between core impact elements. At the same time, the representative characteristic town cases are assessed for their sustainable development potential, and the modified VIKOR technique is applied to clarify the actual problems of the empirical cases, in an attempt to determine whether the development potential and development plan of the characteristic town meet the sustainable development needs from the pre-evaluation mechanism.

Genome-Wide Assessment of Runs of Homozygosity by Whole-Genome Sequencing in Diverse Horse Breeds Worldwide.

In the genomes of diploid organisms, runs of homozygosity (ROH), consecutive segments of homozygosity, are extended. ROH can be applied to evaluate the inbreeding situation of individuals without pedigree data and to detect selective signatures via ROH islands. We sequenced and analyzed data derived from the whole-genome sequencing of 97 horses, investigated the distribution of genome-wide ROH patterns, and calculated ROH-based inbreeding coefficients for 16 representative horse varieties from around the world. Our findings indicated that both ancient and recent inbreeding occurrences had varying degrees of impact on various horse breeds. However, recent inbreeding events were uncommon, particularly among indigenous horse breeds. Consequently, the ROH-based genomic inbreeding coefficient could aid in monitoring the level of inbreeding. Using the Thoroughbred population as a case study, we discovered 24 ROH islands containing 72 candidate genes associated with artificial selection traits. We found that the candidate genes in Thoroughbreds were involved in neurotransmission (CHRNA6, PRKN, and GRM1), muscle development (ADAMTS15 and QKI), positive regulation of heart rate and heart contraction (HEY2 and TRDN), regulation of insulin secretion (CACNA1S, KCNMB2, and KCNMB3), and spermatogenesis (JAM3, PACRG, and SPATA6L). Our findings provide insight into horse breed characteristics and future breeding strategies.

The eQTL colocalization and transcriptome-wide association study identify potentially causal genes responsible for economic traits in Simmental beef cattle.

BACKGROUND: A detailed understanding of genetic variants that affect beef merit helps maximize the efficiency of breeding for improved production merit in beef cattle. To prioritize the putative variants and genes, we ran a comprehensive genome-wide association studies (GWAS) analysis for 21 agronomic traits using imputed whole-genome variants in Simmental beef cattle. Then, we applied expression quantitative trait loci (eQTL) mapping between the genotype variants and transcriptome of three tissues (longissimus dorsi muscle, backfat, and liver) in 120 cattle. RESULTS: We identified 1,580 association signals for 21 beef agronomic traits using GWAS. We then illuminated 854,498 cis-eQTLs for 6,017 genes and 46,970 trans-eQTLs for 1,903 genes in three tissues and built a synergistic network by integrating transcriptomics with agronomic traits. These cis-eQTLs were preferentially close to the transcription start site and enriched in functional regulatory regions. We observed an average of 43.5% improvement in cis-eQTL discovery using multi-tissue eQTL mapping. Fine-mapping analysis revealed that 111, 192, and 194 variants were most likely to be causative to regulate gene expression in backfat, liver, and muscle, respectively. The transcriptome-wide association studies identified 722 genes significantly associated with 11 agronomic traits. Via the colocalization and Mendelian randomization analyses, we found that eQTLs of several genes were associated with the GWAS signals of agronomic traits in three tissues, which included genes, such as NADSYN1, NDUFS3, LTF and KIFC2 in liver, GRAMD1C, TMTC2 and ZNF613 in backfat, as well as TIGAR, NDUFS3 and L3HYPDH in muscle that could serve as the candidate genes for economic traits. CONCLUSIONS: The extensive atlas of GWAS, eQTL, fine-mapping, and transcriptome-wide association studies aid in the suggestion of potentially functional variants and genes in cattle agronomic traits and will be an invaluable source for genomics and breeding in beef cattle.

Regional estimates of nitrogen budgets for agricultural systems in the East African Community over the last five decades.

The great challenge of reducing soil nutrient depletion and assuring agricultural system productivity in low-income countries caused by limited synthetic fertilizer use necessitates local and cost-effective nutrient sources. We estimated the changes of the nitrogen budget of agricultural systems in the East African Community from 1961 to 2018 to address the challenges of insufficient nitrogen inputs and serious soil nitrogen depletion in agricultural systems of the East African Community region. Results showed that total nitrogen input increased from 12.5 kg N ha-1yr-1 in the 1960s to 21.8 kg N ha-1yr-1 in the 2000s and 27 kg N ha-1yr-1 in the 2010s. Total nitrogen crop uptake increased from 12.8 kg N ha-1yr-1 in the 1960s to 18.2 kg N ha-1yr-1 in the 2000s and 21.8 kg N ha-1yr-1 in the 2010s. Soil nitrogen stock increased from -2.0 kg N ha-1yr-1 in the 1960s to -0.5 kg N ha-1yr-1 in the 2000s and 0.3 kg N ha-1yr-1 in the 2010s. Our results allow us to substantiate for the first time that soil nitrogen depletion decreases with increasing input of nitrogen in agricultural systems of the East African Community region. This suggests that increases in nitrogen inputs through biological nitrogen fixation and animal manure are the critical nitrogen management practices to curb soil nitrogen depletion and sustain agricultural production systems in the East African Community region in order to meet food demand for a growing population. Supplementary Information: The online version contains supplementary material available at 10.1007/s13593-023-00881-0.

The systematic analysis and 10-year prediction on disease burden of childhood cancer in China.

Background: There is a lack of in-depth analysis regarding the disease burden of childhood cancer in China. Indeed, this is the first time the topic has been addressed in detail. Drawing on population-based data for the past 30 years, this study systematically analyzes the composition and long-term trend of this disease burden in China. Methods: GBD 2019 contained population-based data from 1990 to 2019 and was prepared using Microsoft Excel 2016. We used AAPC and ARIMA models for trend analysis and prediction formulation. Results: In 2019, there were 45,601 new cases, 9,156 cancer deaths, and 782,530 DALYs in China. From 1990 to 2019, leukemia, together with brain and CNS cancer, invariably ranked highest in terms of new cases, cancer deaths, and DALYs. Leukemia accounted for more than 50%, but decreased over time. By contrast, the proportions for brain and CNS cancer increased. There were significant decreases in the overall incidence, mortality, and DALY rates in China, but these were still higher than the corresponding global average levels. Considering all types of childhood cancer, the incidence rate of testicular cancer showed the biggest increase, and the mortality and DALY rates of leukemia showed the largest decrease. In terms of different age groups, the overall incidence rate of childhood cancers increased in 0 to 4 age group, but it decreased in 5 to 14 age groups. The overall mortality and DALY rates of childhood cancers decreased in all four age groups. Over the next 10 years, the overall incidence rate of childhood cancer will increase, but the overall mortality and DALY rates will decrease. The increase in malignant skin melanoma will comprise the largest rise in the incidence, while the decrease for leukemia will be the largest fall in the incidence, cancer deaths, and DALYs. Conclusion: The disease burden of all childhood cancers in China remains highly serious, especially for certain types of cancer and certain age groups. China should focus more emphatically on the incidence of childhood cancer in future, and it must consistently strengthen investment in the relevant research and medical resources to reduce the disease burden in this field.

Helicopter Emergency Medical Services Performed Extended Focused Assessment With Sonography: Training, Workflow, and Sustainable Quality.

The extended focused assessment of trauma (EFAST) examination is an invaluable tool for the initial evaluation of the trauma patient. Miniaturization of ultrasound has enabled helicopter emergency medical services (HEMS) to use point-of-care ultrasound to care for trauma patients on scene. Our study demonstrated that HEMS crews accurately performed EFAST examinations after the implementation of a novel HEMS EFAST workflow, multifaceted training, and ongoing quality assurance. The HEMS crews' overall sensitivity was 53%, and specificity was 98%. The obtained image quality was highest for the lung, cardiac, and right upper quadrant components of the EFAST. Our results suggest that with a structured multifaceted training program, user-friendly workflow, and ongoing quality assurance, HEMS crews can perform EFAST examinations safely and reliably in the field. This would allow HEMS crews to detect life-threatening, time-sensitive conditions such as a pneumothorax, pericardial effusion, and intraperitoneal hemorrhage. HEMS EFAST has the potential to triage certain trauma patients directly to the operating room or newly emerging hybrid suites, bypassing the emergency room and saving crucial time.

Genome Resource of Ancylobacter pratisalsi E130T: A Novel Plant-Growth-Promoting Bacterium Isolated from the Rhizosphere.

Ancylobacter pratisalsi sp. nov. strain E130T is a Gram-negative, nonmotile, aerobic, and rod-shaped bacterium that was recently isolated from the rhizosphere of Plantago winteri Wirtg. from a natural salt meadow. This strain was described as novel species in genus Ancylobacter; however, information about its complete genome has yet not been reported. In this study, its genome was completely sequenced by PacBio SMRT cell platform, analyzed, and compared with other selected complete genome sequences of Ancylobacter to elucidate its potential plant growth promotion abilities. The genomic analysis revealed that the genome of strain E130T consists of one circular DNA chromosome of 4,618,530 bp with a GC content of 66% and one plasmid of 159,741 bp with a GC content of 64.13%. The entire genome contains 4,322 predicted coding genes, 49 transfer RNAs, and 6 ribosomal RNA genes. Genome analysis identified a siderophore natural product biosynthesis cluster, which produces fuscachelin. Knockout of several key genes in this cluster significantly reduces the plant-growth-promotion ability of the strain E130T. In addition to plant-growth promotion, the strain E130T can grow well on 5% NaCl (wt/vol), indicating that this strain is a potential bioresource for successful production of economic crops in alkaline soil.

A Comparison of Epidemiological Characteristics of Central Nervous System Tumours in China and Globally from 1990 to 2019.

BACKGROUND: Despite their great disease burden, there have been few studies on the epidemiology of central nervous system tumours (CNSTs) in China. We used the latest data updated by GBD to analyse the trends of incidence, mortality, and disability-adjusted life years (DALYs) for CNSTs in China versus globally. METHODS: Epidemiological data on CNSTs were extracted from GBD 2019. We used Joinpoint regression analysis to calculate the magnitude and direction of the trends and the age-period-cohort method to analyse the age, period, and cohort effects of the trend. RESULTS: From 1990 to 2019, the 106.52% increase in Chinese incident cases was higher than the global increase (94.35%). The 67.32% increase in cancer deaths and 16.03% increase in DALYs were lower than the global increases (cancer death: 76.36%; DALYs: 40.06%). The age-standardized incidence rates (ASIRs) in China were higher than the global ASIRs, and the increase in China was higher than that globally. Although the age-standardized mortality rates and age-standardized DALY rates in China were higher, their increases in China were less than those globally. Both in China and globally, the number and incidence, mortality, and DALYs by age group showed a bimodal distribution (younger than 5 years and older), and the peak in the older age group showed a backwards trend. The proportion of incident cases, cancer deaths, and DALYs also increased in the older age group. In the age-period-cohort model, the local drifts in the older age group were above zero. CONCLUSIONS: The burden of CNSTs is very serious in China, and we should pay attention to the key populations, early diagnosis technology, improvements in medical technology, and ways to reduce medical costs. We believe our results could help policymakers allocate resources efficiently to reduce the burden of CNSTs.

Enhancing the Health and Well-Being of People with Chronic Diseases: Assessment and Sustainable Development Planning for Therapeutic Landscapes after Urban Expansion.

Under the influence of economic, environmental, and social structural changes, urban space expands and contracts to varying degrees and the everyday urban landscape changes in response. Over the past 20 years, a large number of cities in China have undergone a brief but rapid urban expansion and are moving toward shrinking cities. Most of these cities are now facing social problems such as an aging population and a high prevalence of chronic diseases. Therefore, the "therapeutic" role and impact of everyday landscapes in these cities need to be examined in the context of urban development processes through appropriate assessment methods. Therefore, this study applies the ANP-mV model to examine the therapeutic nature of everyday urban landscapes in different development periods, with the aim of enhancing the health and well-being of people with chronic diseases. Firstly, this study uses the city of Jinzhou in Northeast China as an example to develop a framework for assessing the therapeutic nature of everyday urban landscapes based on the health care needs of people with chronic diseases; secondly, it examines the therapeutic nature of the former Jinzhou Suburban Riverfront Forest Park as it has developed and evolved over the past 16 years; finally, it explores place-making and regeneration strategies for therapeutic landscapes from the perspectives of dynamic impact and sustainable development to enhance chronic illness patients' well-being. At the theoretical level, this study contributes by providing a methodology and research ideas for examining the "therapeutic" nature of everyday urban landscapes and proposing further development plans for renewal, constructing a framework for assessing therapeutic landscapes, and elucidating the relationship between networks of influence and the relative importance of various assessment dimensions/elements. At the practical application level, the contribution of this study is to provide local policymakers with a key decision basis for the future development planning of the East Lake Forest Park. The aim is to explore landscape creation and regeneration strategies for the East Lake Forest Park in the context of Jinzhou's progressive move toward a shrinking city, in order to sustain the well-being of the chronically ill.

Follow-up of two newborns with c.158G>A (p.Arg53His) mutation in gene and assessment of the site function.

: To investigate the clinical significance of c.158G>A mutation.: The blood phenylalanine (Phe) was continuously monitored in 2 unrelated newborns with suspected hyperphenylalaninimia (HPA) carrying c.158G>A mutation. The cross-species conservation of the mutant amino acid was analyzed using T-Coffee. Swiss-Model software was used to construct a 3D protein structure and the impact of candidate mutations on the secondary structure of the protein product was analyzed. The population carrying rate of the p.Arg53His mutation was analyzed by literature searching. Allelic phenotype values (APV) and genotypic phenotype values (GPV) were used to predict the phenotype associated with the mutation. Two mutations of gene were detected in each newborn: c.611A>G(p.Tyr204Cys), c.158G>A(p.Arg53His) and c.1238G>C(p.Arg413Pro), c.158G>A(p.Arg53His). Two children tolerated normal diet and plasma Phe levels were within the normal range during follow-up. The mother of case 2 was homozygous with p.Arg53His mutation under the condition of long-term normal diet, and the blood Phe concentration and Phe/Tyr were all within the normal range. The mutant amino acids were not highly conserved among the 13 different species. The 3D structural model showed that p.Arg53His mutation reduced the hydrogen bond from 2 to 1 between the 53rd and 49th amino acids of PAH. The allele frequency of p.Arg53His was 0.015 08 in HPA patients and 0.001 621 in normal population, while the prevalence of p.Arg53His allele was highest in the East Asian normal population (0.013 73). The APV and GPV system predicted that the mutation was related to mild HPA(MHP) type. : The different compound heterozygous mutations of p.Arg53His lead to clinical phenotype varieties. The reduction of enzyme activity caused by the mutation of p.Arg53His is not sufficient to cause symptoms of phenylketonuria, so the mutation may be "likely benign".

Unsupervised Machine Learning-Based Analysis of Clinical Features, Bone Mineral Density Features and Medical Care Costs of Rotator Cuff Tears.

PURPOSE: We aim to present unsupervised machine learning-based analysis of clinical features, bone mineral density (BMD) features, and medical care costs of Rotator cuff tears (RCT). PATIENTS AND METHODS: Fifty-three patients with RCT were reviewed, the clinical features, BMD features, and medical care costs were collected and analyzed by descriptive statistics. Furtherly, unsupervised machine learning (UML) algorithm was used for dimensionality reduction and cluster analysis of the RCT data. RESULTS: There were 26 males and 27 females. The patients were divided into four subgroups using the UML algorithm. There were significant differences among four subgroups regarding trauma exposure, full-thickness supraspinatus tendon tears, infraspinatus tendon tear, subscapularis tendon tear, BMD distribution, medial row anchors, lateral row anchors, total medical care costs, and consumables costs. We observed the highest frequency of trauma exposure, infraspinatus tendon tear, subscapularis tendon tear, osteoporosis, the highest number of medial row anchors, lateral row anchors, total medical care costs, and consumables costs in subgroup II. CONCLUSION: The unsupervised machine learning-based analysis of RCT can provide clinically meaningful classification, which shows good interpretability and contribute to a better understanding of RCT. The significance of the results is limited due to the small number of samples, a larger follow-up study is needed to confirm the encouraging results.

The epidemiological trends in the burden of lung cancer attributable to PM2.5 exposure in China.

OBJECTIVE: PM2.5, which is a major contributor to air pollution, has large effects on lung cancer mortality. We want to analyse the long-term trends in lung cancer burden attributable to PM2.5 exposure and provide evidence that can be used for preventive measures and health resource planning. METHODS: Mortality data related to lung cancer were obtained from the Global Burden of Disease (GBD) 2019 project. A joinpoint regression analysis was used to assess the magnitude and direction of the trends in mortality from 1990 to 2019, and the age-period-cohort method was used to analyse the temporal trends in the mortality rate of lung cancer attributable to PM2.5 exposure by age, period, and cohort. RESULTS: From 1990 to 2019, the age-standardized mortality rate (ASMR) attributable to PM2.5 exposure trended slowly upwards, and the ASMR due to ambient PM2.5 exposure (APE) increased significantly, that due to household PM2.5 exposure (HPE) decreased. The longitudinal age curves show that the mortality rates due to PM2.5 exposure among younger individuals were low, and they significantly increased from their levels among those in the 45-49 age group to their levels among those in the over-85 age group. From 1990 to 2019, the period RRs due to APE increased, but those due to HPE decreased. Similar trends were observed in the cohort RRs. The overall net drift per year attributable to PM2.5 exposure was below 0. The local drift values increased with age and were above 0 for the over-80 age groups. The overall net drifts per year were above zero for APE and below zero for HPE. The corresponding results among males were higher than those among females. CONCLUSIONS: In China, the type of air pollution responsible for lung cancer has changed from household air pollution to ambient air pollution. PM2.5 exposure is more harmful among males and older people. Ambient air pollution should be emphasized, and China should strengthen its implementation of effective public policies and other interventions.

Development of the decision tree model for distinguishing individuals of Chinese four surnames from Zhanjiang Han population based on Y-STR haplotypes.

Co-separation studies between surnames and Y chromosome genetic markers are beneficial to revealing population migrations, surname origins, population formation histories and forensic familial searching. Genetic distributions of 27 Y-STRs in Chinese four surnames (Li, Lin, Chen and Huang) from Zhanjiang Han population were investigated. Meanwhile, we tried to develop a decision tree model for surname predictions based on Y-STR haplotypes. Allelic frequencies of 27 Y-STRs showed that unique alleles were only observed in a certain surname; besides, some alleles displayed higher frequencies in a certain surname than those in other surnames, implying these alleles might be employed as the useful indicators for surname predictions. Haplotype match probability values of 27 Y-STRs in these surnames revealed that the system could be used as a valuable tool for forensic male identification. The developed decision tree model performed well for the training set with the accuracy of 0.9860 and obtained the relatively high accuracy (>0.70) for surname predictions of the testing set. To sum up, we explored the power of the machine learning to the surname predictions based on obtained Y-STR haplotypes, which showed promising application values in forensic familial searching.

Genomic sequencing analysis reveals copy number variations and their associations with economically important traits in beef cattle.

Copy number variation (CNV) represents a major source of genetic variation, which may have potentially large effects, including alternating gene regulation and dosage, as well as contributing to gene expression and risk for normal phenotypic variability. We carried out a comprehensive analysis of CNV based on whole genome sequencing in Chinese Simmental beef cattle. Totally, we found 9313 deletion and 234 duplication events, covering 147.5 Mb autosomal regions. Within them, 257 deletion events of high frequency overlapped with 193 known RefGenes. Among these genes, we observed several genes were related to economically important traits, like residual feed intake, immune responding, pregnancy rate and muscle differentiation. Using a locus-based analysis, we identified 11 deletions and 1 duplication, which were significantly associated with three traits including carcass weight, tenderloin and longissimus muscle area. Our sequencing-based study provided important insights into investigating the association of CNVs with important traits in beef cattle.

Socio-economic disparity in the global burden of occupational noise-induced hearing loss: an analysis for 2017 and the trend since 1990.

OBJECTIVES: To evaluate socio-economic disparity in the global burden of occupational noise-induced hearing loss (ONIHL) using disability-adjusted life-years (DALYs). METHODS: The numbers of DALYs due to ONIHL, age-standardised DALY rates and national human development index (HDI) data from 1990 to 2017 were collected. The relationship between the age-standardised DALY rates and the 2017 HDI was analysed. A concentration index (CI) and a relative index of inequality (RII) were calculated to evaluate the trend in socio-economic disparity in the burden of ONIHL for the period 1990-2017. RESULTS: From 1990 to 2017, the global DALYs due to ONIHL increased from 3.3 to 6.0 million, with the highest growth occurring in low-income countries (110.7%). Age-standardised DALY rates due to ONIHL were negatively associated with the HDI (ß = -0.733, p<0.001), and these rates were significantly higher in countries with a lower HDI. From 1990 to 2017, the trend in between-country inequality was flat with little fluctuation, the CIs stayed near -0.17, and the RIIs remained near 0.35. CONCLUSIONS: Over the past few decades, low-income countries have experienced the most rapid growth in DALYs worldwide. A widening socio-economic disparity has persisted in the global burden of ONIHL, with a higher burden in lower socio-economic countries. These data suggest that more prevention programmes and healthcare services should be provided for developing countries.

Genome-Wide Assessment of Runs of Homozygosity in Chinese Wagyu Beef Cattle.

Runs of homozygosity (ROH) are continuous homozygous regions that generally exist in the DNA sequence of diploid organisms. Identifications of ROH leading to reduction in performance can provide valuable insight into the genetic architecture of complex traits. Here, we evaluated genome-wide patterns of homozygosity and their association with important traits in Chinese Wagyu beef cattle. We identified a total of 29,271 ROH segments from 462 animals. Within each animal, an average number of ROH was 63.36 while an average length was 62.19 Mb. To evaluate the enrichment of ROH across genomes, we initially identified 280 ROH regions by merging ROH events across all individuals. Of these, nine regions containing 154 candidate genes, were significantly associated with six traits (body height, chest circumference, fat coverage, backfat thickness, ribeye area, and carcass length; p < 0.01). Moreover, we found 26 consensus ROH regions with frequencies exceeding 10%, and several regions overlapped with QTLs, which are associated with body weight, calving ease, and stillbirth. Among them, we observed 41 candidate genes, including BCKDHB, MAB21L1, SLC2A13, FGFR3, FGFRL1, CPLX1, CTNNA1, CORT, CTNNBIP1, and NMNAT1, which have been previously reported to be related to body conformation, meat quality, susceptibility, and reproductive traits. In summary, we assessed genome-wide autozygosity patterns and inbreeding levels in Chinese Wagyu beef cattle. Our study identified many candidate regions and genes overlapped with ROH for several important traits, which could be unitized to assist the design of a selection mating strategy in beef cattle.

Current status of the clinical use of PD-1/PD-L1 inhibitors: a questionnaire survey of oncologists in China.

BACKGROUND: The purpose of the present study was to obtain information on the use of PD-1/PD-L1 inhibitors by oncologists in China through a national questionnaire survey. METHODS: Between the 7th and 25th of July in 2019, a questionnaire designed by the Chinese Society of Clinical Oncology Immuno-Oncology (CSCO IO) Committee on the current status of the use of PD-1/PD-L1 inhibitors was distributed online and offline to cancer-related medical departments in thirty different provinces and autonomous regions of China. The national questionnaire consisted of three sections as follows: general information, current status of the application of PD-1/PD-L1 inhibitors in the clinic, and oncologists' concerns regarding utilization. RESULTS: The valid response rate of the current status survey was 76.3%. The proportion of senior doctors (physician-in-charge or a more superior position for more than 3 years) among the respondents was relatively high (67.0% in 588). Of the respondents, 59.2% had prescribed PD-1/PD-L1 inhibitors during clinical treatment, and the most frequent reason for not prescribing these inhibitors was the choice "do not understand the mechanism and the efficacy of PD-1/PD-L1 inhibitors". In addition, 77.9% of the prescribers used the medications in an off-label situation, and the most important motivation for this use was the fact that "there were indications abroad but not domestically". In addition, 77.9% of the prescribers believed that "immunotherapy-related adverse effects could be controlled or intervened through follow-up management". The prescribers were mostly concerned about "how to identify pseudoprogression and hyperprogression" and "immunity-related adverse effects management". CONCLUSION: The present study highlights the current status of PD-1/PD-L1 inhibitors in China. Increasing numbers of medical oncologists are interested in PD-1/PD-L1 inhibitors, and they are in need of immunotherapy education.

Treatment patterns and direct medical costs of metastatic colorectal cancer patients: a retrospective study of electronic medical records from urban China.

Objectives: To describe direct medical costs associated with each line of treatment among metastatic colorectal cancer (mCRC) patients in China.Methods: Electronic medical records between 2011 and 2016 were extracted from 12 tertiary hospitals in China for adult patients who initiated third-line treatment at least nine months before the end of data collection. Direct medical costs included costs of wards, diagnostic tests, surgical procedures, special materials, drugs and others. Costs were assessed by line of treatment, and drug costs were further breakdown for patients receiving chemotherapy alone and those receiving chemo- and biologics-combined therapy.Results: Of the 404 mCRC patients, the mean age was 55 years old and 62% were male. Oxaliplatin- and irinotecan-based regimens dominated first- and second-line treatment, respectively (44 and 37%). From first- to second- to third-line, the proportion of patients receiving targeted biologics increased from 18% at first-line and 12% at second-line to 34% at third-line; median number of treatment cycles reduced from 6 to 4 and to 2. The corresponding mean direct medical costs per person per cycle increased from $2,514 to $2,678 to $5,121. Mean drug costs per cycle increased from $2,314 to $2,673 to $4,316 among patients receiving chemotherapy alone and from $3,245 to $2,717 to $6,533 among patients receiving chemo- and biologics-combined therapy.Conclusions: Before 2017, mCRC patients in China did not receive the maximum benefits of precision medicine breakthroughs. Reduced treatment cycles and increased costs per cycle from first- to third-line suggested poor healthcare resource utilization. With earlier initiation and more treatment cycles, targeted biologics may better demonstrate their effectiveness among Chinese patients. Our findings reflected the urgent need to increase drug accessibility in China before 2017 and underscore that including innovative biologics into Chinese health insurance plans can reduce patients' economic burden and improve the management of mCRC.

Disparity in clinical outcomes between pure and combined pulmonary large-cell neuroendocrine carcinoma: A multi-center retrospective study.

OBJECTIVES: The 2015 World Health Organization classification defines pulmonary large-cell neuroendocrine carcinoma (LCNEC) as a high-grade neuroendocrine carcinoma. However, the clinical characteristics and prognostic factors of pure LCNEC and combined LCNEC remain unclear. Hence, we performed a multi-center retrospective study to compare the clinical outcomes of pure versus combined LCNEC. MATERIALS AND METHODS: Data from 381 patients with pulmonary LCNEC admitted to 17 Chinese institutes between 2009 and 2016 were collected retrospectively. Clinical characteristics and prognosis were analyzed among patients receiving adjuvant (adjuvant group; n = 56) and first-line (first-line group; n = 146) chemotherapy, as well as among patients receiving small cell lung cancer (SCLC) and non-SCLC (NSCLC) chemotherapy regimens. The Kaplan-Meier method and multivariable Cox regression were used to identify clinicopathological variables that might influence patient outcomes. RESULTS: Expression levels of neuroendocrine markers (synaptophysin, chromogranin-A, CD56) were associated with patients' prognosis in the total study cohort. In the adjuvant group, median disease-free survival was non-significantly longer for SCLC-based regimens than for NSCLC-based regimens (P = 0.112). In the first-line group, median progression-free survival was significantly longer for SCLC-based regimens than for NSCLC-based regimens (11.5 vs. 7.2 months, P = 0.003). Among patients with combined LCNEC, adenocarcinoma was the most common combined component, accounting for 70.0 % of cases. Additionally, median overall survival was non-significantly shorter for combined LCNEC than for pure LCNEC (P = 0.083). CONCLUSION: The SCLC regimen is a more effective choice, as either first-line or adjuvant chemotherapy, when compared to the NSCLC regimen for LCNEC treatment. Further studies are needed to clarify the survival differences between patients with pure-, and combined LCNEC.