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The research and development (R&D) of industrial generic technologies (IGTs) is a collaborative innovation involving many stakeholders. The key to ensure the R&D success of IGT is how to effectively mobilize various stakeholders to take a more active approach to increase the degree of joint efforts and cooperation. Considering that the degree of effort and cooperation among the stakeholders, and the commonality of IGT and the difficulty of subsequent commercialization have an important impact on its success, in this article, we exploit the thought and methods of gray-target decision model, group negotiations, and game theory to design a government-subsidies incentive mechanism. Besides, considering the government's special role in the R&D, we introduce the stakeholders’ risk preferences of IGTs and discuss the decision-making behaviors of different stakeholders under the circumstances of either cooperation or noncooperation. At the end, we confirm the rationality and validity of our model by using a real case.

Background: This study was to investigate the prevalence of preoperative rim enhancement, and its association with clinicopathological features, relapse, and survival profiles in Chinese basal-like...

Background: Vincristine (VCR) is a chemotherapeutic drug commonly used in the treatment of Colorectal Cancer (CRC). However, VCR drug resistance may result in reduced efficacy and even failure of chemotherapy in CRC treatment. MiRNA has been demonstrated to be associated with the sensitivity of tumor cells to chemotherapy. Objective: This study aimed to identify a novel miRNA-14669 that can reverse vincristine resistance and sensitize drug-resistant colorectal cancer cells. Methods: High-throughput sequencing was performed to screen miRNAs that are associated with VCR drug resistance, and qRT-PCR was used for further validation. The miRNA mimic and inhibitor were designed and transfected into HCT-8,HCT-116 and HCT-8/VCR cells. Wound healing test examined the effect of the miRNA on the migration of colorectal cancer cells. Flow cytometry was used to evaluate cell apoptosis of HCT-8 cells. Survivin, Bcl-2, GST3, MDR1 and MRP1 expressions were detected by Western blot. Results: The expression of miRNA-14669 in HCT-8/VCR cells was 1.925 times higher than that of the HCT-8 cells. After transfecting with mimic miRNA, HCT-8 and HCT-116 cells showed an increased survival rate. The survival rate of HCT-8/VCR cells decreased by transfection of inhibitor. The inhibitor also sensitized HCT-8 and HCT-116 cells to VCR or 5-Fluorouracil (5-FU). The migratory ability of HCT-8 and HCT-116 cells increased by miRNA mimic while reduced by miRNA inhibitor. Overexpression of miRNA-14669 reduced apoptosis, while downregulation of miRNA- 14669 increased cell apoptosis in HCT-8 cells. The mechanism of the miRNA involved in drug resistance may be attributed to apoptosis of tumor cells, detoxification of GST3 and drug efflux induced by MDR1 and MRP1. PI3K / AKT is the signaling pathway related to drug resistance. Conclusion: We identified a novel miRNA-14669 that may be associated with the chemotherapeutic resistance in CRC cells.

BackgroundPatients with frailty are at a high risk of poor health outcomes, and frailty has been explored as a predictor of adverse events, such as perioperative complications, readmissions, falls, disability, and mortality in the neurosurgical literature. However, the precise relationship between frailty and neurosurgical outcomes in patients with brain tumor has not been established, and thus evidence-based advancements in neurosurgical management. The objectives of this study are to describe existing evidence and conduct the first systematic review and meta-analysis of the relationship between frailty and neurosurgical outcomes among brain tumor patients.MethodsSeven English databases and four Chinese databases were searched to identify neurosurgical outcomes and the prevalence of frailty among patients with a brain tumor, with no restrictions on the publication period. According to the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis and the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines, two independent reviewers employed the Newcastle–Ottawa scale in cohort studies and JBI Critical Appraisal Checklist for Cross-sectional Studies to evaluate the methodological quality of each study. Then random-effects or fixed-effects meta-analysis was used in combining odds ratio (OR) or hazard ratio (RR) for the categorical data and continuous data of neurosurgical outcomes. The primary outcomes are mortality and postoperative complications, and secondary outcomes include readmission, discharge disposition, length of stay (LOS), and hospitalization costs.ResultsA total of 13 papers were included in the systematic review, and the prevalence of frailty ranged from 1.48 to 57%. Frailty was significantly associated with increased risk of mortality (OR = 1.63; CI = 1.33–1.98; p p I2 = 33%), nonroutine discharge disposition to a facility other than home (OR = 1.72; CI = 1.41–2.11; p p = 0.001), and high hospitalization costs among brain tumor patients. However, frailty was not independently associated with readmission (OR = 0.99; CI = 0.96–1.03; p = 0.74).ConclusionFrailty is an independent predictor of mortality, postoperative complications, nonroutine discharge disposition, LOS, and hospitalization costs among brain tumor patients. In addition, frailty plays a significant potential role in risk stratification, preoperative shared decision making, and perioperative management.Systematic review registrationPROSPERO CRD42021248424

Risk-informed safety classification of structures, systems and components (SSCs) is very important for ensuring the safety and economic efficiency of nuclear power plants (NPPs). However, previous methods for safety classification of SSCs do not take the plant operating modes or the operational process of SSCs into consideration, thus cannot concentrate on the safety and economic efficiency accurately. In this contribution, a new method for safety classification of SSCs based on the categorization of plant operating modes is proposed, which considers the NPPs operating history to improve the economic efficiencies while maintaining the safety. According to the time duration of plant configurations in plant operating modes, average importances of SSCs are accessed for an NPP considering the operational process, and then safety classification of SSCs is performed for plant operating modes. The correctness and effectiveness of the proposed method is demonstrated by application in an NPP's safety classification of SSCs.

Implantation timing is key for a successful pregnancy. Short delay in embryo implantation caused by targeted gene ablation produced a cascading problem in the later stages of the pregnancy. Although several delayed implantation models have been established in wild mice, almost none of them is suitable for investigating the delay on the late events of pregnancy. Here, we report a new delayed implantation model established by the intraperitoneally administration of letrozole at 5 mg/kg body weight on the day 3 of pregnancy. In these mice, initiation of implantation was induced at will by the injection of estradiol (E2). When the estradiol (3 ng) was injected on day 4 of pregnancy (i.e., without delay), the embryo implantation restarted, and the pregnancy continued normally. However, high dose of estrogen (25 ng) caused compromised implantation. We also found that only 67% of the female mice could be pregnant normally and finally gave birth when the injection of estradiol (3 ng) was on day 5 of pregnancy (i.e., one day delay). Most of the failed pregnancies had impaired decidualization, decreased plasma progesterone levels and compromised angiogenesis. Progesterone supplementation could rescue decidualization failure in the mice. Collectively, we established a new model of delayed implantation by letrozole, which can be easily used to study the effect and mechanisms of delay of embryo implantation on the progression of late pregnancy events.

The 2019 Kidney Disease Outcome Quality Initiative (K/DOQI) guideline recommended evaluating arteriovenous fistula (AVF) malfunction risks primarily based on clinical monitoring, which can be assisted with the value of vascular access flow (Qa). Nevertheless, Qa thresholds recommended by different guidelines vary, ranging from 300 to 500 ml/min. This study investigated the optimal Qa threshold to predict future functional patency in AVFs with Qa 500 ml/min.Both the clinical indicators of access dysfunction and the Qa value were monitored in patients receiving hemodialysis by the radiocephalic AVF. Routine access flow surveillance was performed by the ultrasound dilution method (HD03, Transonic Inc.). The development of clinically significant indicators of access dysfunction, which necessitated percutaneous transluminal angiography (PTA) to maintain functional patency, was analyzed in this cohort.Among the enrolled 302 patients, Qa of 52 patients was under 500 ml/min. These 52 patients received 2 Qa measurements during the follow-up period. Of these 52 patients, serial Qa of 17 patients varied trivially and their AVF remained functional. Multivariable logistic regression analysis revealed that a low Qa per ideal body weight (IBW) is an independent predictor of AVF functional loss. Receiver operating characteristic curve analysis of Qa/IBW in predicting future AVF functional loss revealed that the best cutoff value of Qa is 7.1 times the IBW.For radiocephalic AVFs with Qa 500 ml/min, the minimally required Qa to maintain access function is associated with individual IBW. The IBW-based Qa threshold assessment would allow more flexibility in the treatment of patients and reduce unnecessary invasive measures.

Introduction Breast cancer (BC) is the most widely studied disease due to its higher prevalence, heterogeneity and mortality. Objectives This study aimed to compare female BC trends among 21 world regions and globally over 28 year of data and to assess the association between sociodemographic transitions and female BC risks. Methods We used Global burden of disease study data and measure the female BC burden according to 21 world regions and sociodemographic indices (SDI). Age-period-cohort (APC) analysis was used to estimate time and cohort trend of BC in different SDI regions. Results By world regions, age-standardised rate of female BC incidence were high in high-income-North America (ASR, 92.9; (95 %UI, 89.2, 96.6)), Western Europe (84.7; (73.4, 97.2)) and Australia (86; (81.7, 90.2)) in 2017. Whereas this rate was significantly increased by 89.5% between 1990 and 2017 in East Asia. We observed negative association between SDI and death, and DALYs in 25th and below percentiles of death and DALYs for the worldwide regions. Further, there was observed a strong negative correlation between SDI and case fatality percent (r2017 = −0.93; r1990 = −0.92) in both 2017 and 1990 worldwide and highest case fatality percentage was observed in Central Sub-Saharan Africa. Overall, the risk of case-fatality rate tends to decrease most noticeably in high middle SDI countries, and the reduction of the risk of case-fatality rate in the recent cohort was the lowest in the low SDI countries. Conclusions Remarkable variations exist among various regions in BC burden. There is a need to reduce the health burden from BC in less developed and under developing countries, because under-developed countries are facing higher degree of health-related burden. Public health managers should execute more classified and cost-effective screening and treatment interferences to lessen the deaths caused by BC, predominantly among middle and low SDI countries having inadequate healthcare supplies.

Disorders of consciousness (DoC) happen frequently in various brain injuries. Their detection helps timely treatment for better survival outcomes of DoC patients. It is conventionally undertaken via clinical examinations, typically behavioural assessments. However, these neurological examinations consume significant resources of manpower and time, making continuous DoC monitoring practically infeasible. To address this issue, a computer-aided approach is proposed in this article for automated DoC detection through extracting knowledge from electroencephalogram (EEG) signals. It introduces a new connectivity measure: Power Spectral Density Difference (PSDD) incorporating with a recursive Cosine function (CPSDD). Then, the approach classifies brain-injured patients into DoC (i.e., positive) and wakefulness (i.e., negative) classes through an ensemble of support vector machines (EOSVM), which is a type of machine-learning methods. It is further applied to a dataset of 607 patients with brain injuries. Our classification results show that the EOSVM classifier with the new connectivity measure CPSDD has achieved the best classification performance among 12 connectivity measures. For a setting of 97% majority voting from all SVMs, the EOSVM has diagnosed, in high confidence, 35% of patients with the accuracy, sensitivity, and specificity of 98.21%, 100%, and 95.79%, respectively. Thus, the classifier EOSVM incorporating with the new connectivity measure CPSDD is a promising tool for automatic detection of DoC in brain injuries.

As we all know, file and free space fragmentation negatively affect file system performance. F2FS is a file system designed for flash memory. However, it suffers from severe fragmentation due to out-of-place updates and the highly synchronous, multi-threaded writing behaviors of applications. The adaptive reserved space (ARS) scheme chooses some files instead of all files to update in the reserved space which collects file features associated with fragmentation to construct datasets and uses decision trees to pick reserved files. However, ARS processes file features according to write fds. On the one hand, fds and files are mapped many-to-many, so there is an issue in mapping reserved files according to reserved fds that a normal file is selected as a reserved file. On the other hand, the mapping of files to fds for big data traces is confusing. We propose ARST that traces the file of write fd to optimize ARS. Moreover, by selecting time-independent file features, ARST predicts whether files with little historical information are reserved to maximize the performance improvement brought by reserving space. Besides, adjustable reserved space and dynamic reservation strategies are adopted. We implement ARST on a HiKey960 development platform and a commercial smartphone with slight space and file creation time overheads. Experimental results show that ARST reduces file and free space fragmentation dramatically and improves file system performance. ARST reduces the running time of realistic workloads by up to 94.28% than F2FS with in-place updates and outperforms ARS by up to 49.06% for Wechat.

To build small and efficient neural networks for hyperspectral image (HSI) classification, this letter presents a depthwise separable residual neural network (ResNet). This approach, motivated by the popular MobileNet architecture, decomposes the traditional spatial-spectral convolution operation into a spatial-independent pointwise spectral convolution and a spectral-independent depthwise spatial convolution. It allows the separation of spectral and spatial information in HSI and also greatly reduces the network size to prevent the overfitting issue. To better preserve the class boundaries and edges, the proposed ResNet is integrated into a maximum a posteriori (MAP) framework to allow the use of the conditional random field (CRF) model. The experiment results on benchmark HSI scene demonstrate that the proposed ResNet compares favorably with several popular deep learning HSI classifiers and that the ResNet-CRF approach achieves higher accuracy and better boundaries among neighboring classes.

Retinal angiogenesis is a critical process for normal retinal function. However, uncontrolled angiogenesis can lead to pathological neovascularization (NV), which is closely related to most irreversible blindness-causing retinal diseases. Understanding the molecular basis behind pathological NV is important for the treatment of related diseases. Twist-related protein 1 (TWIST1) is a well-known transcription factor and principal inducer of epithelial-mesenchymal transition (EMT) in many human cancers. Our previous study showed that Twist1 expression is elevated in pathological retinal NV. To date, however, the role of TWIST1 in retinal pathological angiogenesis remains to be elucidated. To study the role of TWIST1 in pathological retinal NV and identify specific molecular targets for antagonizing pathological NV, we generated an inducible vascular endothelial cell (EC)-specific Twist1 transgenic mouse model (Tg-Twist1iEC+). Whole-mount retinas from Tg-Twist1iEC+ mice showed retarded vascular progression and increased vascular density in the front end of the growing retinal vasculature, as well as aneurysm-like pathological retinal NV. Furthermore, overexpression of Twist1 in the ECs promoted cell proliferation but disturbed cell polarity, thus leading to uncontrolled retinal angiogenesis. TWIST1 promoted pathological NV by activating the Wnt/β-catenin signaling pathway and inducing the expression of NV formation-related genes, thereby acting as a ‘valve’ in the regulation of pathological angiogenesis. This study identified the critical role of TWIST1 in retinal pathological NV, thus providing a potential therapeutic target for pathological NV.

A novel spatial singularity-exponent-domain multiresolution imaging (SSMRI) method is proposed in this article. It is aimed at improving the image processing ability for the single-channel synthetic aperture radar (SAR), thereby acquiring the robust image feature for SAR target detection at the very low SNR. Combining the 2-D singularity power spectrum (SPS) and the 2-D pseudo-Wigner-Ville distribution (PWVD), the SSMRI method is derived. Consequently, the single-channel SAR images are transformed to obtain spatial multiresolution SAR images with respect to the singularity exponent. Furthermore, the separability of the SAR image target in the space of the singularity exponent is analyzed, and the separability theorem in the sense of SSMRI is proved. In particular, under the background of GWN and fractal noise, the separability of SAR image targets based on SSMRI processing is studied. In addition, the stability and robustness of SSMRI-SAR feature extraction are demonstrated. On this basis, a maritime SAR ship target detection method based on SSMRI is put forward in the extremely low SNR condition. The experiment results on the SAR-Ship-Dataset indicate that the proposed method is superior in performance to the traditional CFAR or 2-D-SPS method. Especially when SNR =-30 dB, the detection performance with more than 99.4% can be achieved.

BACKGROUND: It is necessary to develop an accurate non-invasive method to determine the histopathological growth pattern (HGP) of colorectal liver metastasis (CRLM) before surgery. The present study aimed to identify various HGPs of CRLM by magnetic resonance imaging (MRI) features. METHODS: This retrospective study included 53 chemo-naïve patients with CRLM between December 2013 and September 2019. The HGPs of CRLM were assessed according to the international consensus guidelines, and were classified as either replacement HGP (rHGP) or non-rHGP. The MRI features of CRLM were retrospectively reviewed in consensus by two radiologists. The differences of MRI features between rHGP and non-rHGP tumors were compared by using Chi-square test and Student’s t-test. The Spearman or Pearson correlation analysis was performed to determine the correlation between different MRI features. A receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic ability. RESULTS: Of the 53 chemo-naïve patients (mean age, 60.11±9.85 years; age range, 38–86 years), 12 were diagnosed as rHGP, while 41 were diagnosed as non-rHGP. Rim enhancement were more common in rHGP than in non-rHGP (P

AIM Left ventricular hypertrophy and impaired systolic and diastolic function are commonly seen in patients with chronic kidney disease, but relationships between the disorders and cardiovascular outcomes are not well established among the patients. METHODS Totally, 2020 patients with chronic kidney disease stages 1-4 were used in the analysis. Left ventricular hypertrophy was defined by left ventricular mass index >49.2 g/m2.7 in men and >46.7 g/m2.7 in women. Incident heart failure, non-heart failure cardiovascular events, and all-cause mortality were recorded longitudinally. Cox proportional hazards regression model was used to evaluate the association between the echo parameters and the outcomes, with death treated as the competing risk event for the cardiovascular events. RESULTS After a median follow-up of 4.5 years, 53 heart failure, 76 non-heart failure cardiovascular events and 82 deaths occurred. No overall association was found between left ventricular hypertrophy and subsequent heart failure, but the relationship was significant among patients with no diabetes with the multivariable adjusted hazard ratio of 3.66 (95% confidence interval: 1.42-9.46). Ejection fraction

Vision-language navigation (VLN) is the task of navigating an embodied agent to carry out natural language instructions inside real 3D environments. In this paper, we study how to address three critical challenges for this task: the cross-modal grounding, the ill-posed feedback, and the generalization problems. First, we propose a novel Reinforced Cross-Modal Matching (RCM) approach that enforces cross-modal grounding both locally and globally via reinforcement learning (RL). Particularly, a matching critic is used to provide an intrinsic reward to encourage global matching between instructions and trajectories, and a reasoning navigator is employed to perform cross-modal grounding in the local visual scene. Evaluation on a VLN benchmark dataset shows that our RCM model significantly outperforms baseline methods by 10 percent on Success Rate weighted by Path Length (SPL) and achieves the state-of-the-art performance. To improve the generalizability of the learned policy, we further introduce a Self-Supervised Imitation Learning (SIL) method to explore and adapt to unseen environments by imitating its own past, good decisions. We demonstrate that SIL can approximate a better and more efficient policy, which tremendously minimizes the success rate performance gap between seen and unseen environments (from 30.7 to 11.7 percent).

Hepatocellular carcinoma (HCC) is a very deadly disease. HCC initiation and progression involve multiple genetic events, including the activation of proto-oncogenes and disruption of the function of specific tumor suppressor genes. Activation of oncogenes stimulates cell growth and survival, while loss-of-function mutations of tumor suppressor genes result in unrestrained cell growth. In this review, we summarize the new findings that identified novel proto-oncogenes and tumor suppressors in HCC over the past five years. These findings may inspire the development of novel therapeutic strategies to improve the outcome of HCC patients.

Background Invasive infection with group B streptococcus (GBS) can lead to intrauterine infection, and GBS can also spread via vertical transmission between mother and infant, resulting in adverse pregnancy outcomes. This study aimed to investigate the effects of GBS colonization in late gestation on vaginal micro-ecology, pregnancy outcomes and neonatal outcome. Methods One hundred and twenty pregnant women in the third trimester infected with GBS and 120 healthy counterparts who underwent a prenatal examination in the obstetrics department of the study hospital from June 2019 to December 2020 were selected for inclusion in the study. Vaginal micro-ecological index, mode of delivery, adverse pregnancy outcomes and neonatal Apgar score were compared between the two groups. Results The incidence rates of vaginal micro-ecological disorders, intrauterine infection and neonatal infection were significantly higher in the GBS group compared with the control group. The incidence rates of neonatal fetal distress and pathological jaundice were much higher in the GBS group compared with the control group. The neonatal Apgar score was markedly lower in the GBS group compared with the control group. Conclusions GBS infection is correlated with the vaginal micro-environment. GBS colonization in late pregnancy has adverse effects on vaginal micro-ecology and pregnancy outcome.

A Fabry-Perot interferometer (FPI) temperature sensor was proposed by splicing a self-made hollow core anti-resonance fiber (HC-ARF) between two single mode fibers (SMFs). The HC-ARF was 2 mm long and one SMF was 20 mm in length. The SMF end face was coated with an Au film. When temperature varied from 45 °C to 85 °C, a sensitivity of 81.1 pm/°C was obtained at the waveband of 1550 nm∼1555 nm. When temperature varied from 35 °C to 95 °C, a sensitivity of 138.8 pm/°C was obtained at the waveband of 1571 nm∼1581 nm. Theoretical analysis suggested that the sensitivity of this proposed sensor can be easily adjusted by varying the length of the Au-coated SMF via the Vernier effect, which was confirmed by a subsequent experiment where the SMF length was varied from 20 mm to 170 mm. This work offers a simple sensitivity control method, and the proposed sensor is easy to manufacture, compact in structure, and convenient in performance control, which can be applied for a wide range of biological and chemical applications.

BACKGROUND Many patients with primary membranous nephropathy have severe proteinuria unresponsive to optimized renin-angiotensin-aldosterone system inhibitors (RAASi). We evaluated the efficacy and safety of hydroxychloroquine as an adjunctive agent in membranous nephropathy (MN) treatments. METHODS We prospectively recruited 126 patients with biopsy-proven primary membranous nephropathy and urinary protein 1-8 g/day while receiving optimized RAASi treatment for ≥ 3 months and well-controlled blood pressure. Forty-three patients received hydroxychloroquine and RAASi (hydroxychloroquine-RAASi group), and 83 patients received RAASi alone (RAASi group). Treatment responses, including proteinuria reduction, complete and partial remission rates, and autoantibody against phospholipase A2 receptor (anti-PLA2R) levels, were compared between the two groups at 6 months and over the long term. RESULTS At 6 months, the effective response rate (proteinuria reduction > 30%) (57.5% vs. 28.9%, P = 0.002), clinical remission rate (35.0% vs. 15.7%, P = 0.015), and percentage change in proteinuria (- 51.7% vs. - 21.9%, P

Objective: This study aims to evaluate the risk factors for subjective recurrence and complications of patients who underwent transvaginal synthetic mesh surgery. Design: This retrospective cohort study included patients who received transvaginal mesh (TVM) surgery between January 2005 and June 2019. Methods: The information of patients was collected, including basic characteristics, subjective recurrence, and mesh-related complications. The clinical characteristics of patients with and without subjective recurrence were compared. The sexual activities of patients before and after the operation were recorded. SPSS 20.0 was used for the statistical analysis. Results: A total of 257 patients were included. Among them, 62 (24.1%) patients were lost to follow-up. The median follow-up time was 80 months (12 months, 170 months). Finally, 195 patients were followed up, 11 (5.6%) patients had a subjective recurrence of pelvic organ prolapse, and 26 (13.3%) patients had mesh-related complications (11 patients with de novo pain and 15 patients with mesh exposure). We found significant differences in age (68.9 ± 5.1 vs. 63.4 ± 5.8 years old), years of postmenopause (17.5 ± 6.3 vs. 13.3 ± 6.9 years), previous hysterectomy (27.3% vs. 6.0%), and concomitant hysterectomy (45.5% vs. 81.0%) between patients with and without subjective recurrence (p < 0.05). The mesh exposure proportion of patients with total vaginal mesh (47.6%) was significantly higher than that with anterior vaginal mesh (2.9%) (p < 0.05). Furthermore, 6.7% of sexually active patients reported de novo dyspareunia. Limitation: The investigators could only record the subjective recurrence of patients, and thus there is a lack of objective recurrence data. Conclusion: Age, years of postmenopause, and previous hysterectomy are risk factors for subjective recurrence of TVM surgery; however, concomitant hysterectomy is a protective factor. Mesh exposure is the most common complication, especially for total vaginal mesh repair surgery.

Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.

Background:. Obesity and insulin resistance (IR) are common features of polycystic ovary syndrome (PCOS). Metformin (MET) increases insulin sensitivity, but it is associated with unsatisfactory weight loss. The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in patients with diabetes. This study aimed to explore the therapeutic effects of exenatide once-weekly (QW) combined with MET on body weight, as well as metabolic and endocrinological parameters in overweight/obese women with PCOS. Methods:. Fifty overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups: MET (500 mg three times a day [TID]) or combination treatment (COM) (MET 500 mg TID, exenatide 2 mg QW) for 12 weeks. The primary outcomes were anthropometric changes associated with obesity, and the secondary outcomes included changes in reproductive hormone levels, glucose and lipid metabolism, and C-reactive protein. Results:. Forty (80%) patients completed the study. COM therapy was superior to MET monotherapy in reducing weight (P = 0.045), body mass index (BMI) (P = 0.041), and waist circumference (P = 0.023). Patients in the COM group on an average lost 3.8 ± 2.4 kg compared with 2.1 ± 3.0 kg in the MET group. In the COM group, BMI and waist circumference decreased by 1.4 ± 0.87 kg/m2 and 4.63 ± 4.42 cm compared with 0.77 ± 1.17 kg/m2 and 1.72 ± 3.07 cm in the MET group, respectively. Moreover, levels of fasting glucose, oral glucose tolerance test (OGTT) 2-h glucose, and OGTT 2-h insulin were significantly lower with COM therapy than with MET (P

Objective To evaluate the operative methods and clinical results of surgical treatment in a case series of 10 patients with hemophilic pseudotumors. Methods Ten patients with hemophilic pseudotumors who received surgical resection treatment in our hospital from October 2017 to June 2020 were retrospectively reviewed. All patients were hemophilia A (factor VIII deficiency).The age range was 20–51 years. Preoperative imaging examination revealed the size of irregular mass from 8.2 cm× 3.3 cm× 2.3 cm to 22.3 cm× 15.5 cm× 17.0 cm. With the supplementary of recombinant coagulation factor VIII, five cases received complete resection; one received resection and skin grafting; one received cytoreduction surgery as the pseudotumor closing to iliac vessel and nerve; three cases received complete resection and construction as bone destruction. The perioperative variables were recorded and all the patients were followed in the outpatient clinic. Clinical and radiological assessments were conducted. Results In these patients, the average intraoperative blood loss volume was 783.1 mL (range, 240–2100 mL). Six patients received blood transfusion during perioperative period. The average duration of surgery was 140.7 min (range, 110–240 min). All wounds healed smoothly and there was no infection or chronic sinus formation. The average length of hospital stay was 16.3 days (range, 12–25 days). There is no iatrogenic vascular nerve injury in our series. Complete follow‐up was performed in all patients. Mean follow‐up duration was 14.2 months (range, 6–26 months). One patient with pseudotumor in the thigh had a recurrence 1 year after operation, then secondary operation was performed. In three cases who received complete resection and construction, patient 8 obtained bone graft and late fixation. X‐ray examination showed bone formation in the lesion at the 2‐year follow‐ups after operation. Patient 9 underwent knee replacement, his left knee showed flexion deformity in preoparation. At the last follow‐up, range of motion was improved from 0° to 40° compared with preoperative status. Patient 10 had pseudotumor in the distal femur, received long bone graft and intramedullary nail fixation. Conclusions Surgical resection for hemophilic pseudotumors is an effective and safe method. The choice of surgical procedure must be individualized according to the localization and progress of pseudotumor., Pseudotumors occur in 1% to 2% of patients with severe hemophilia and they are associated with encapsulated blood after bleeding in soft tissue or subperiosteum. There are three kinds of pseudotumors: Type I, a simple cyst which develops within the muscle; Type II, a cyst that develops in a muscle and has an extensive blood supply in region of its attachment to a bone, which leads to compression to cortex and thinning of the cortex of bone; Type III, which starts as subperiosteal hemorrhage and destroys the structure of the underlining bone, and is considered as true pseudotumor, and originate from the bone itself. Due to the enlarged cyst resulting in compression of bone, pseudotumors often lead to bone structure erosion and fracture. Treatment for this type of hemophilic complication is very difficult due to its rarity.

Background Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. Methods A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. Results 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. Conclusions Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.

Background Severe COVID-19 caused by SARS-CoV-2 should closely be cared because of the relatively high mortality rate. If SARS-CoV-2 could be cleared as soon as possible, the mortality rate might lower. In the present study, we analyzed factors which might be related to the clearance of SARS-CoV-2. Methods One hundred and twenty-eight severe COVID-19 cases were enrolled. All of them had been isolated and treated at Shenzhen Third People’s Hospital because they were positive for nucleic acid of SARS-CoV-2 tested by qRT-PCR. Their baseline clinical characteristics and antiviral regimens were collected and analyzed, respectively. Results Of the 128 enrolled severe COVID-19 cases, unfortunately 3 died. The mean viral duration of all patients was 23.5 (range 17−32) days. All patients achieved viral clearance during 9 weeks. 13.4% of patients achieved viral clearance within 2 weeks, and 63.0% of patients achieved viral clearance within 4 weeks. The combined regimens of three or more antiviral drugs, the use of invasive mechanical ventilation, and late admission might be related to the delay of viral clearance within 2 weeks. The use of arbidol, the use of invasive mechanical ventilation, and late admission might be related to the delay of viral clearance within 4 weeks. Patients often had a prolonged course of COVID-19 and hospitalization, and were more likely transferred to intensive care unit (ICU) for treatment, if they could not clear SARS-CoV-2 during 23 days. Conclusion Severe COVID-19 cases should be admitted to hospital as soon as possible. The combined regimens of three or more antiviral drugs might not be useful for viral clearance, and should be performed carefully and cautiously.

Objective To investigate the associations of mitochondrial DNA (mtDNA) genetic variants with SLE susceptibility, glucocorticoid (GC) efficacy and prognosis. Methods Our study was done in two stages. First, we performed whole mitochondrial genome sequencing in 100 patients and 100 controls to initially screen potential mtDNA variants associated with disease and GC efficacy. Then, we validated the results in an independent set of samples. In total, 605 SLE patients and 604 normal controls were included in our two-stage study. A two-stage efficacy study was conducted in 512 patients treated with GCs for 12 weeks. We also explored the association between mtDNA variants and SLE prognosis. Results In the combined sample, four mtDNA variants (A4833G, T5108C, G14569A, CA514-515-) were associated with SLE susceptibility (all PBH Conclusion We identified novel mtDNA genetic variants that were associated with SLE susceptibility, GC efficacy, and prognosis. Interactions between mtDNA variants and environmental factors were related to SLE risk and GC efficacy. Our findings provide important information for future understanding of the occurrence and development of SLE.

This study uses China’s Growth Enterprises Market (GEM) listed companies from 2011 to 2017 as samples to examine the impact of industrial policies on innovation in startups from three dimensions, namely, selective industrial policies, government subsidies, and financial support. The results show that selective industrial policies have no effect on the innovation output of startups. Financial support can significantly promote the innovation output of entrepreneurial enterprises; structural differences exist in the impact of government subsidies on the innovation of entrepreneurial enterprises. The influence of industrial policy on the innovation of entrepreneurial enterprises depends on the research and development intensity of enterprises, the level of regional economic development, the leadership structure of enterprises, and other factors. This study’s findings have significant practical significance for the implementation of a national innovation-driven development strategy and to guide industrial policies that better promote enterprise innovation.

In practice, both comprehensive hospital (e.g. AAA hospital) and primary hospital (e.g. community hospital) can exist in healthcare system, where the comprehensive hospital can provide a guaranteed...

Publisher Copyright: © 2021 The Authors. Published by American Chemical Society The global prevalence of antibiotic resistance genes (ARGs) is of increasing concern as a serious threat to ecological security and human health. Irrigation with sewage and farmland application of manure or biosolids in agricultural practices introduce substantial selective agents such as antibiotics and toxic metals, aggravating the transfer of ARGs from the soil environment to humans via the food chain. To address this issue, a hyperaccumulator (Sedum plumbizincicola) combined with biochar amendment was first used to investigate the mitigation of the prevalence of ARGs in cadmium and oxytetracycline co-contaminated soil by conducting a pot experiment. The addition of biochar affected the distribution of ARGs in soil and plants differently by enhancing their prevalence in the soil but restraining transmission from the soil to S. plumbizincicola. The planting of S. plumbizincicola resulted in an increase in ARGs in the soil environment. A structural equation model illustrated that mobile genetic elements played a dominant role in shaping the profile of ARGs. Taken together, these findings provide a practical understanding for mitigating the prevalence of ARGs in this soil system with complex contamination and can have profound significance for agricultural management in regard to ARG dissemination control.

Robot-assisted needle insertion guided by 2D ultrasound (US) can effectively improve the accuracy and success rate of clinical puncture. To this end, automatic and accurate needle-tracking methods are important for monitoring puncture processes, avoiding the needle deviating from the intended path, and reducing the risk of injury to surrounding tissues. This work aims to develop a framework for automatic and accurate detection of an inserted needle in 2D US image during the insertion process. We propose a novel convolutional neural network architecture comprising of a two-channel encoder and single-channel decoder for needle segmentation using needle motion information extracted from two adjacent US image frames. Based on the novel network, we further propose an automatic needle detection framework. According to the prediction result of the previous frame, a region of interest of the needle in the US image was extracted and fed into the proposed network to achieve finer and faster continuous needle localization. The performance of our method was evaluated based on 1000 pairs of US images extracted from robot-assisted needle insertions on freshly excised bovine and porcine tissues. The needle segmentation network achieved 99.7% accuracy, 86.2% precision, 89.1% recall, and an F1-score of 0.87. The needle detection framework successfully localized the needle with a mean tip error of 0.45 ± 0.33 mm and a mean orientation error of 0.42° ± 0.34° and achieved a total processing time of 50 ms per image. The proposed framework demonstrated the capability to realize robust, accurate, and real-time needle localization during robot-assisted needle insertion processes. It has a promising application in tracking the needle and ensuring the safety of robotic-assisted automatic puncture during challenging US-guided minimally invasive procedures.

Fluid inhomogeneous distribution affects heat transfer efficiency in the plate-fin heat exchanger (PFHE). In order to improve fluid uniform distribution in the exchanger, the irregular-shaped hole leading flow structure (IHLFS) was proposed for solving fluid inhomogeneous distribution among different layers of PFHE. The inlet distributor with irregular-shaped holes was designed according to different inlet flow velocities aiming at improving fluid uniform distribution. The results on fluid flow and heat transfer characteristics were carried out by the methods of CFD and experimental analysis, and finally, the fluid flow characteristics in inlet section of PFHE with IHLFS were achieved. Comparing with round hole leading flow structure (RHLFS), it can be observed that fluid distribution in PFHE with IHLFS is more uniform than that with round hole, however, the dynamic pressure increases accordingly and finally, increases the ratio of heat transfer and dynamic pressure. The comparison results also demonstrate that the IHLFS can improve fluid distribution, decrease fluid impact in inlet section of PFHE and finally, improve heat transfer enhancement.

Radiofrequency ablation (RFA) guided by X-ray images aims to relieve herniated disc pain with minimal invasiveness and fast recovery. It requires an accurate and fast positioning of the puncture needle. We propose a teleoperated robotic system for percutaneous puncture to support RFA. We report the kinematics modelling and workspace analysis of the proposed system, which comprises preliminary and accurate positioning mechanisms. Preliminary positioning mechanism automatically drives the needle to the puncture area, and accurate positioning is then achieved by teleoperation under the guidance of X-ray images. We calculate the teleoperation workspace of the robot system using a spatial search algorithm and quantitatively analyze the optimal structural parameters aiming to maximize the workspace. The workspace of the proposed robot system complies with clinical requirements to support RFA.

The objective of this paper is to study the curative effect of music combined with hypnosis on labor pains during childbirth. Based on the algorithm of data mining, we randomly selected 100 women who delivered babies in obstetric units from October 2020 to June 2021, set the control group and the observation group, obtained the relevant clinical data through comparison, and analyzed the value of music combined with hypnotic analgesia midwifery in obstetrics. The results showed that the number of spontaneous delivery cases in the observation group was higher than that in the control group ( P < 0.05 ) and the delivery time in the observation group was better than that in the control group ( P < 0.05 ). It is proved that music combined with hypnosis can effectively improve the rate of natural childbirth and shorten the overall labor time, so as to guarantee the health of mother and child.

Purpose Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. Materials and Methods TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate. Results The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was 8 and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR‒positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs. Conclusion Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR‒positive status could be a significant biomarker for predicting ICI response in patients.

Objective Secondary outcomes from a published feasibility and acceptability trial were examined to explore the effect of bright white light (BWL) on quality of life (QoL) and depressive symptoms compared to dim red light (DRL) control in adolescents and young adults (AYAs) receiving cancer-directed therapy. Methods Fifty-one AYAs (12–22 years, 51% male) newly diagnosed with cancer were randomized to receive 8 weeks of BWL (n = 26) or DRL (n = 25). The CDI-2 (total score, negative mood/physical symptoms, interpersonal problems, ineffectiveness, and negative self-esteem) and parent- and self-report PedsQL (total score and subscales of physical, emotional, social, and school QoL) were completed at multiple timepoints. Results BWL produced improvements in self-reported total depression (d = −.64; 95% confidence interval [CI] = −1.26, −0.01), negative self-esteem (d = −.80; 95% CI = −1.43, −.14), negative mood/physical symptoms (d = −.73; 95% CI = −1.36, −0.08), ineffectiveness (d = −.43; 95% CI = −1.04, .19), total self-reported QoL (d = .41; 95% CI = −.16, .96), emotional (d = .78; 95% CI = .19, 1.37), school functioning (d = .48; 95% CI = −.09, 1.04), and parent-reported school functioning (d = .66; 95% CI = 0.02, 1.33). BWL reported a greater rate of improvement than DRL for total depression (β = .49, p < .05) and self-esteem (β = .44, p < .05), and parent-reported school functioning (β = −1.68, p < .05). Conclusions BWL improved QoL and depressive symptoms for AYAs with cancer. These findings will inform larger randomized controlled trials.

Recently, pretrained language models, such as Bert and XLNet, have rapidly advanced the state of the art on many NLP tasks. They can model implicit semantic information between words in the text. However, it is solely at the token level without considering the background knowledge. Intuitively, background knowledge influences the efficacy of text understanding. Inspired by this, we focus on improving model pretraining by leveraging external knowledge. Different from recent research that optimizes pretraining models by knowledge masking strategies, we propose a simple but general method to transfer explicit knowledge with pretraining. To be specific, we first match knowledge facts from a knowledge base (KB) and then add a knowledge injunction layer to a transformer directly without changing its architecture. This study seeks to find the direct impact of explicit knowledge on model pretraining. We conduct experiments on 7 datasets using 5 knowledge bases in different downstream tasks. Our investigation reveals promising results in all the tasks. The experiment also verifies that domain-specific knowledge is superior to open-domain knowledge in domain-specific task, and different knowledge bases have different performances in different tasks.

Jipang Zhan, Xuhua Tang, Fang Wang, Jiande Han Department of Dermatology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of ChinaCorrespondence: Jiande HanDepartment of Dermatology, the First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Second Road, Guangzhou, Guangdong, 510080, People’s Republic of ChinaTel +86-138-0274-3924Fax +86-020-8293-8840Email hanjd@mail.sysu.edu.cnPurpose: Unlike eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the relationship between eicosatetraenoic acid (ETA) and psoriasis remains unclear. Therefore, We performed a cross-sectional study in the general American population to investigate the association between daily dietary ETA, EPA, and DHA intake and the risk of psoriasis.Participants and Methods: This study applied data from the National Health and Nutrition Examination Survey (NHANES) 2003– 2006 and 2009– 2014. Dietary n3 polyunsaturated fatty acids (PUFA) were calculated based on two 24-hour dietary recall interviews. We defined psoriasis by responding to the question “Have you ever been told by a doctor or other health care professional that you had psoriasis?”. Multivariable logistic regression analysis, trend tests, subgroup analysis, and interaction tests were used to evaluate the associations of ETA, EPA, and DHA intake with the risk of psoriasis, respectively.Results: A total of 15,733 participants were included in this study. In our optimal multivariate-adjusted model, the odds ratio (OR) with 95% confidence interval (CI) of psoriasis were 0.30 (0.12, 0.88), 1.92 (0.78, 4.74), 1.28 (0.72, 2.27) for daily dietary ETA, EPA, and DHA intake, respectively. Trend tests showed a dose–effect relationship between daily dietary ETA intake and the lower risk of psoriasis. Subgroup analysis and tests for interaction showed that the association was stable in different subgroups.Conclusion: Our study revealed that there might be a dose–effect association of daily dietary ETA intake with the lower risk of psoriasis in American adults.Keywords: psoriasis, diet, eicosatetraenoic acid, long-chain n3 polyunsaturated fatty acid, NHANES

Objective To evaluate the body mass index and neurologic development of 1-2 years offspring born to mothers with polycystic ovary syndrome. Study design A case-control study. Place and duration of study Dongyang Women and Children's Hospital, Zhejiang Province, China, between June 2018 and January 2019. Methodology A total of 145 children were included in the final analysis, including 16 daughters of mothers with PCOS, 13 sons of mothers with PCOS, 55 daughters of mothers without PCOS and 61 sons of mothers without PCOS. Developmental assessments for each child were conducted, including anthropometric measurements and ability developments using the Denver developmental screening test. Results The body mass index of children was significantly lower in polycystic ovary syndrome group than control group (p=0.022). Children of mothers with polycystic ovary syndrome and control group had no significant differences in the outcomes of the Denver developmental screening test (all p >0.05). Conclusion Maternal polycystic ovary syndrome may affect body mass index of offspring aged 1-2 years and had no negative effects on neurologic development. However, this conclusion may be limited due to the small sample size. Key Words: Neurologic development, Polycystic ovary syndrome, Offspring, Denver development screening test, Body mass index.

As an early-stage tumor biomarker, microRNA (miRNA) has clinical application potential and its sensitive and accurate detection is significant for early tumor diagnosis. In this study, a photoelectrochemical (PEC) biosensing platform was fabricated for ultrasensitive miRNA-141 detection, which is based on a photocurrent polarity-switchable system using CdS quantum dots (QDs) in the presence of a 5,10,15,20-tetrakis (4-aminophenyl)-21H,23H-porphine (Tph-2H)-coated glassy carbon electrode (GCE). As an excellent photoactive material, Tph-2H has a narrow band gap that effectively gathers photoelectrons under visible light irradiation and improves the transfer ability of photogenerated electrons. Further, the detection sensitivity of miRNA-141 could be significantly improved by combining an enzyme-assisted recycle amplification reaction and a magnetic bead-based separation strategy. The proposed photocurrent polarity-switchable PEC biosensor could efficiently eliminate the false-positive or false-negative signals and achieve a wide linear response range from 1 fM to 1 nM with a low detection limit of 0.33 fM for miRNA-141, providing a potentially alternative solution for detecting other biomarkers in bioanalysis and clinical diagnosis.

Brain metastases (BMs) and bone metastases seriously affect the prognosis of lung cancer patients. How to optimize the use of existing targeted drugs is an important way to address the clinical needs of the central nervous system in the individualized treatment of non-small cell lung cancer (NSCLC). In this report, we describe an NSCLC patient with BMs who survived for 58 months, which is the longest survival case among lung cancer patients with BMs. The patient was initially diagnosed with lung cancer more than 5 years ago with simultaneous brain, bone, and lung metastases. After gefitinib resistance, she received osimertinib in sequence with no progress for 58 months in total and maintained very good quality of life.

Background There were few studies exploring the associations between depressive symptoms, anxiety symptoms and health-related quality of life (HRQoL) in the general population, especially in resource limited area. The aims of this study were to assess the associations between depressive symptoms, anxiety symptoms, their comorbidity and HRQoL in rural area. Methods A total of 23,496 eligible participants from Henan rural cohort were included. The Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder-2 (GAD-2) were employed to assess depressive and anxiety symptoms, respectively. HRQoL was measured via European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L). Tobit regression and generalized linear model were utilized to explore the associations between depressive symptoms, anxiety symptoms, their comorbidity and HRQoL. Results A total of 1320 individuals were identified as depressive symptoms with a prevalence rate of 5.62%, while 1198 participants were classified as anxiety symptoms with a prevalence rate of 5.10%. After multiple adjustment, the regression coefficients (β) and 95% confidence interval (CI) of utility index for depressive and anxiety symptoms were − 0.166 (− 0.182, − 0.149) and − 0.132 (− 0.149, − 0.114), respectively. The β and 95% CI of VAS score for depressive and anxiety symptoms were − 7.65 (− 8.60, − 6.70) and − 5.79 (− 6.78, − 4.80), respectively. Additionally, the comorbidity was strongly associated with low utility index and VAS score. These findings were observed robustly in men and women. Conclusion Depressive symptoms, anxiety symptoms and their comorbidity were associated with low HRQoL in rural population, which needed further efforts on preventive and treatment interventions. Clinical trial registration The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July, 2015.

Tillering contributes greatly to grain yield in wheat. Investigating the mechanisms of tillering provides a theoretical foundation and genetic resources for the molecular breeding of wheat. The regulation of tillering is a complex molecular process that involves a multitude of factors. Little is known about the molecular mechanisms in the wheat genome, although progress has been made in rice. Here we review the developmental characteristics of tillers and summarize current knowledge of the roles of endogenous and environmental factors in wheat tillering. We propose directions for future studies and advanced technologies to be used for gene identification and functional studies.