ABSTRACT IMPACT: This work will standardize necessary image pre-processing for diagnostic and prognostic clinical workflows dependent on quantitative analysis of conventional magnetic resonance imaging. OBJECTIVES/GOALS: Conventional magnetic resonance imaging (MRI) poses challenges for quantitative analysis due to a lack of uniform inter-scanner voxel intensity values. Head and neck cancer (HNC) applications in particular have not been well investigated. This project aims to systematically evaluate voxel intensity standardization (VIS) methods for HNC MRI. METHODS/STUDY POPULATION: We utilize two separate cohorts of HNC patients, where T2-weighted (T2-w) MRI sequences were acquired before beginning radiotherapy for five patients in each cohort. The first cohort corresponds to patients with images taken at various institutions with a variety of non-uniform acquisition scanners and parameters. The second cohort corresponds to patients from a prospective clinical trial with uniformity in both scanner and acquisition parameters. Regions of interest from a variety of healthy tissues assumed to have minimal interpatient variation were manually contoured for each image and used to compare differences between a variety of VIS methods for each cohort. Towards this end, we implement a new metric for cohort intensity distributional overlap to compare region of interest similarity in a given cohort. RESULTS/ANTICIPATED RESULTS: Using a simple and interpretable metric, we have systematically investigated the effects of various commonly implementable VIS methods on T2-w sequences for two independent cohorts of HNC patients based on region of interest intensity similarity. We demonstrate VIS has a substantial effect on T2-w images where non-uniform acquisition parameters and scanners are utilized. Oppositely, it has a modest to minimal impact on T2-w images generated from the same scanner with the same acquisition parameters. Moreover, with a few notable exceptions, there does not seem to be a clear advantage or disadvantage to using one VIS method over another for T2-w images with non-uniform acquisition parameters. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results inform which VIS methods should be favored in HNC MRI and may indicate VIS is not a critical factor to consider in circumstances where similar acquisition parameters can be utilized. Moreover, our results can help guide downstream quantitative imaging tasks that may one day be implemented in clinical workflows.

Severe fever with thrombocytopenia syndrome (SFTS) is a disease with a high case-fatality rate that is caused by infection with the SFTS virus (SFTSV). Five electronic databases were systematically searched to identify relevant articles published from 1 January 2011 to 1 December 2019. The pooled rates with 95% confidence interval (CI) were calculated by a fixed-effect or random-effect model analysis. The results showed that 92 articles were included in this meta-analysis. For the confirmed SFTS cases, the case-fatality rate was 0.15 (95% CI 0.11, 0.18). Two hundred and ninety-six of 1384 SFTS patients indicated that they had been bitten by ticks and the biting rate was 0.21 (95% CI 0.16, 0.26). The overall pooled seroprevalence of SFTSV antibodies among the healthy population was 0.04 (95% CI 0.03, 0.05). For the overall seroprevalence of SFTSV in animals, the seroprevalence of SFTSV was 0.25 (95% CI 0.20, 0.29). The infection rate of SFTSV in ticks was 0.08 (95% CI 0.05, 0.11). In conclusion, ticks can serve as transmitting vectors of SFTSVs and reservoir hosts. Animals can be infected by tick bites, and as a reservoir host, SFTSV circulates continuously between animals and ticks in nature. Humans are infected by tick bites and direct contact with patient secretions.

Klebsiella pneumoniae is a common pathogen associated with nosocomial infections and is characterised serologically by capsular polysaccharide (K) and lipopolysaccharide O antigens. We surveyed a total of 348 non-duplicate K. pneumoniae clinical isolates collected over a 1-year period in a tertiary care hospital, and determined their O and K serotypes by sequencing of the wbb Y and wzi gene loci, respectively. Isolates were also screened for antimicrobial resistance and hypervirulent phenotypes; 94 (27.0%) were identified as carbapenem-resistant (CRKP) and 110 (31.6%) as hypervirulent (hvKP). isolates fell into 58 K, and six O types, with 92.0% and 94.2% typeability, respectively. The predominant K types were K14K64 (16.38%), K1 (14.66%), K2 (8.05%) and K57 (5.46%), while O1 (46%), O2a (27.9%) and O3 (11.8%) were the most common. CRKP and hvKP strains had different serotype distributions with O2a:K14K64 (41.0%) being the most frequent among CRKP, and O1:K1 (26.4%) and O1:K2 (17.3%) among hvKP strains. Serotyping by gene sequencing proved to be a useful tool to inform the clinical epidemiology of K. pneumoniae infections and provides valuable data relevant to vaccine design.

Beef cattle are often fed high-concentrate diet (HCD) to achieve high growth rate. However, HCD feeding is strongly associated with metabolic disorders. Mild acid treatment of grains in HCD with 1% hydrochloric acid (HA) followed by neutralization with sodium bicarbonate (SB) might modify rumen fermentation patterns and microbiota, thereby decreasing the negative effects of HCD. This study was thus aimed to investigate the effects of treatment of corn with 1% HA and subsequent neutralization with SB on rumen fermentation and microbiota, inflammatory response and growth performance in beef cattle fed HCD. Eighteen beef cattle were randomly allocated to three groups and each group was fed different diets: low-concentrate diet (LCD) (concentrate : forage = 40 : 60), HCD (concentrate : forage = 60 : 40) or HCD based on treated corn (HCDT) with the same concentrate to forage ratio as the HCD. The corn in the HCDT was steeped in 1% HA (wt/wt) for 48 h and neutralized with SB after HA treatment. The animal trial lasted for 42 days with an adaptation period of 7 days. At the end of the trial, rumen fluid samples were collected for measuring ruminal pH values, short-chain fatty acids, endotoxin (or lipopolysaccharide, LPS) and bacterial microbiota. Plasma samples were collected at the end of the trial to determine the concentrations of plasma LPS, proinflammatory cytokines and acute phase proteins (APPs). The results showed that compared with the LCD, feeding the HCD had better growth performance due to a shift in the ruminal fermentation pattern from acetate towards propionate, butyrate and valerate. However, the HCD decreased ruminal pH and increased ruminal LPS release and the concentrations of plasma proinflammatory cytokines and APPs. Furthermore, feeding the HCD reduced bacterial richness and diversity in the rumen. Treatment of corn increased resistant starch (RS) content. Compared with the HCD, feeding the HCDT reduced ruminal LPS and improved ruminal bacterial microbiota, resulting in decreased inflammation and improved growth performance. In conclusion, although the HCD had better growth performance than the LCD, feeding the HCD promoted the pH reduction and the LPS release in the rumen, disturbed the ruminal bacterial stability and increased inflammatory response. Treatment of corn with HA in combination with subsequent SB neutralization increased the RS content and helped counter the negative effects of feeding HCD to beef steers.

Prion diseases, or Transmissible Spongiform Encephalopathies (TSEs), are a group of fatal neurodegenerative disorders associated with a conformational transformation of the cellular prion protein (PrPC) into a self-feplicating and proteinase K (PK)-resistant conformer, scrapie PrP (PrPSc). Aggregates of PrPSc around neurons lead to neuropathologyical change including neuronal loss, astrogliosis, spongiform degeneration and deposition of amyloid plaques. Currently no effective treatment for prion disease exists. The development of novel therapeutic strategies against prion diseases has become a priority. Several reports have demonstrated that passive and active immune-based therapy can significantly prolong the incubation period of prionoses in vivo, and also some anti-PrP monoclonal can prevent PrP peptide toxicity in vitro. In this study, we have first time identified and purified anti-PrP antibodies from human intravenous immunoglobulin (IVIG) by using PrP peptide affinity chromatography column. The ratio of anti-PrP antibody and IVIG is about 1:1200. In vitro study indicates these anti-PrP antibodies strongly block PrP A117V peptide fibril formation and disrupt formation of fibrillar structures. Furthermore, these antibodies almost completely prevented neurotoxicity of PrP A117V peptide in cultured rat cerebellar granule neuron cultures (CGN). In contrast, immunoglobulins depleted of anti-PrP antibodies had little effect on PrP fibril formation or protection of neuronal cells. Our study suggests that human anti-PrP antibodies may interfere with the pathogenesis of prion disease and these purified antibodies may be a potential therapeutic agent to prevent or slow prion disease progression.

Tuberculosis (TB) is the leading cause of death among infectious diseases. China has a high burden of TB and accounted for almost 13% of the world's cases of multi-drug resistant (MDR) TB. Spinal TB is one reason for the resurgence of TB in China. Few large case studies of MDR spinal TB in China have been conducted. The aim of this research was to observe the epidemiological characteristics of inpatients with MDR spinal TB in six provinces and cities of China from 1999–2015. This is a multicentre retrospective observational study. Patients' information was collected from the control disease centre and infectious disease database of hospitals in six provinces and cities in China. A total of 3137 patients with spinal TB and 272 patients with MDR spinal TB were analysed. The result showed that MDR spinal TB remains a public health concern and commonly affects patients 15–30 years of age (34.19%). The most common lesions involved the thoracolumbar spine (35.66%). Local pain was the most common symptom (98.53%). Logistic analysis showed that for spinal TB patients, reside in rural district (OR 1.79), advanced in years (OR 1.92) and high education degree (OR 2.22) were independent risk factors for the development of MDR spinal TB. Women were associated with a lower risk of MDR spinal TB (OR 0.48). The most common first-line and second-line resistant drug was isoniazid (68.75%) and levofloxacin (29.04%), respectively. The use of molecular diagnosis resulted in noteworthy clinical advances, including earlier initiation of MDR spinal TB treatment, improved infection control and better clinical outcome. Chemotherapy and surgery can yield satisfactory outcomes with timely diagnosis and long-term treatment. These results enable a better understanding of the MDR spinal TB in China among the general public.

Glutathione S-transferases (GSTs) are a detoxifying enzyme family that is essential for parasite blood-feeding and survival, and represent potential targets for hookworm vaccine development. Multiple GST-encoding complementary DNAs (cDNAs) have been cloned from Ancylostoma caninum and Necator americanus, but there are no reports about the cloning of this enzyme from Ancylostoma ceylanicum, the animal-derived zoonotic hookworm. To study the molecular nature and tissue localization of GST of A. ceylanicum (Ace-GST), we designed primers based on the GST gene sequence of A. ceylanicum in GenBank, amplified the Ace-GST cDNA by reverse transcription polymerase chain reaction, and analysed its homology and genetic evolution relationship. The amplified product was cloned into the pET-32a vector and transformed into Escherichia coli BL21 (DE3) for expression. To prepare anti-GST polyclonal antibodies, the recombinant protein was purified and used to immunize Kunming mice. The level of immunoglobulin G (IgG) antibody in the serum of immunized mice was detected by indirect enzyme-linked immunosorbent assay, and the Ace-GST localization in adult worm was determined using the immunofluorescence method. The results showed that the full-length cDNA encoding Ace-GST was 468 bp, which had the highest homology with Ac-GST-1 (60.1%) and clustered into one branch (v-class) with Ac-GST-1 and Na-GST-1 in a phylogenetic tree. Mice immunized with recombinant Ace-GST showed specific IgG antibody response. Immunolocalization revealed that natural Ace-GST is mainly located in the epidermis, muscle and intestine of the adult. These results may lay a foundation for further studies on the biological function of Ace-GST.

Crystal structure and electronic structure of YMnO3 were investigated by X-ray diffraction and transmission electron microscopy related techniques. According to the density of states (DOS), the individual interband transitions to energy loss peaks in the low energy loss spectrum were assigned. The hybridization of O 2p with Mn 3d and Y 4d analyzed by the partial DOS was critical to the ferroelectric nature of YMnO3. From the simulation of the energy loss near-edge structure, the fine structure of O K-edge was in good agreement with the experimental spectrum. The valence state of Mn (+3) in YMnO3 was determined by a comparison between experiment and calculations.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Triploid and pentaploid breeding is of great importance in agricultural production, but it is not always easy to obtain double ploidy parents. However, in fishes, chromosome ploidy is diversiform, which may provide natural parental resources for triploid and pentaploid breeding. Both tetraploid and hexaploid exist in Schizothorax fishes, which were thought to belong to different subfamilies with tetraploid Percocypris fishes in morphology, but they are sister genera in molecule. Fortunately, the pentaploid hybrid fishes have been successfully obtained by hybridization of Schizothorax wangchiachii (♀, 2n = 6X = 148) × Percocypris pingi (♂, 2n = 4X = 98). To understand the genetic and morphological difference among the hybrid fishes and their parents, four methods were used in this study: morphology, karyotype, red blood cell (RBC) DNA content determination and inter-simple sequence repeat (ISSR). In morphology, the hybrid fishes were steady, and between their parents with no obvious preference. The chromosome numbers of P. pingi have been reported as 2n = 4X = 98. In this study, the karyotype of S. wangchiachii was 2n = 6X = 148 = 36m + 34sm + 12st + 66t, while that the hybrid fishes was 2n = 5X = 123 = 39m + 28sm + 5st + 51t. Similarly, the RBC DNA content of the hybrid fishes was intermediate among their parents. In ISSR, the within-group genetic diversity of hybrid fishes was higher than that of their parents. Moreover, the genetic distance of hybrid fishes between P. pingi and S.wangchiachii was closely related to that of their parental ploidy, suggesting that parental genetic material stably coexisted in the hybrid fishes. This is the first report to show a stable pentaploid F1 hybrids produced by hybridization of a hexaploid and a tetraploid in aquaculture.

The Weihe Basin is an intracontinental rift basin in central China that provides an ideal location for studying the interactions between regional tectonics and monsoonal climate change. In this paper, we present detrital zircon U–Pb ages from sediments from Core LYH drilled in the northern margin of the basin. We use these to illuminate changing sediment transport processes, provenance and palaeo-environments during the Quaternary. The sediments are dominated by zircon age groups of 100–400 Ma and 400–550 Ma, and three secondary age peaks at 700–1100 Ma, 1700–2100 Ma and 2400–2600 Ma. Multidimensional scaling plots support the conclusion that the Central Loess Plateau and the Luo River are the dominant sources of sediments to the core site. Before c. 1.06 Ma, the Qinling Mountains and the Wei River, as well as the Yellow River, had minor influence on the sedimentation at the core site. These results are consistent with the existence of a palaeolake prior to 1.06 Ma, which allowed sediments supplied to the south and east edge of the basin to be reworked to the northern side of the Weihe Basin. Subsequently, the Luo River has provided a steady source of sediments to the northern Weihe Basin.

This study aims to investigate the prevalence and genotype distribution of anal human papillomavirus (HPV) infection among men with different sexual orientations with or without human immunodeficiency virus (HIV) in China. A cross-sectional study was conducted during 2016–2017 in Taizhou City, Zhejiang Province. Convenient sampling was used to recruit male participants from HIV voluntary counselling and testing clinics and Center for Disease Control and Prevention. A face-to-face questionnaire interview was administered and an anal-canal swab was collected for HPV genotyping. A total of 160 HIV-positive and 113 HIV-negative men participated in the study. The prevalence of any type HPV was 30.6% for heterosexual men, 74.1% for homosexual and 63.6% for bisexual men among HIV-positive participants, while the prevalence was 8.3%, 29.2% and 23.8% respectively among HIV-negatives. The most prevalent genotypes were HPV-58 (16.9%), HPV-6 (15.6%) and HPV-11 (15.0%) among HIV-positive men, and were HPV-16 (4.4%), HPV-52 (4.4%) and HPV-6 (3.5%) among HIV-negative men. Having ever had haemorrhoids and having ever seen blood on tissue after defaecation was associated with HPV infection. One-fourth of the HPV infections in this study population can be covered by the quadrivalent vaccine in market. The highly prevalent anal HPV infection among men especially HIV-infected men calls for close observation and further investigation for anal cancer prevention.

The seasonality of individual influenza subtypes/lineages and the association of influenza epidemics with meteorological factors in the tropics/subtropics have not been well understood. The impact of the 2009 H1N1 pandemic on the prevalence of seasonal influenza virus remains to be explored. Using wavelet analysis, the periodicities of A/H3N2, seasonal A/H1N1, A/H1N1pdm09, Victoria and Yamagata were identified, respectively, in Panzhihua during 2006–2015. As a subtropical city in southwestern China, Panzhihua is the first industrial city in the upper reaches of the Yangtze River. The relationship between influenza epidemics and local climatic variables was examined based on regression models. The temporal distribution of influenza subtypes/lineages during the pre-pandemic (2006–2009), pandemic (2009) and post-pandemic (2010–2015) years was described and compared. A total of 6892 respiratory specimens were collected and 737 influenza viruses were isolated. A/H3N2 showed an annual cycle with a peak in summer–autumn, while A/H1N1pdm09, Victoria and Yamagata exhibited an annual cycle with a peak in winter–spring. Regression analyses demonstrated that relative humidity was positively associated with A/H3N2 activity while negatively associated with Victoria activity. Higher prevalence of A/H1N1pdm09 and Yamagata was driven by lower absolute humidity. The role of weather conditions in regulating influenza epidemics could be complicated since the diverse viral transmission modes and mechanism. Differences in seasonality and different associations with meteorological factors by influenza subtypes/lineages should be considered in epidemiological studies in the tropics/subtropics. The development of subtype- and lineage-specific prevention and control measures is of significant importance.

Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.