bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Control of Iron Bioavailability is Independent from Iron Concentration in a Diverse Winter Wheat Mapping Population
Authors: Wright Tally , Gardner Keith , Glahn Raymond , Milner Matthew
Published: January 2021

Background: Anemia is thought to affect up to 1.6 billion people worldwide. One of the major contributors to low iron (Fe) absorption is a higher proportion of cereals compared to meats and pulse crops in people’s diets. This has now become a problem in both the developed and developing world, as a result of both modern food choice and food availability. Bread wheat accounts for 20% of the calories consumed by humans and is an important source of protein, vitamins and minerals meaning it could be a major vehicle for bringing more bioavailable Fe into the diet. Results: To investigate whether breeding for higher concentrations of Fe in wheat grains could help increase Fe absorption, a multiparent advanced generation intercross (MAGIC) population, encompassing more than 80% of UK wheat polymorphism, was grown over two seasons in the UK. The population was phenotyped for both Fe concentration and Fe bioavailability using an established Caco-2 cell bioassay. It was found that increasing Fe levels in the grains was not correlated with higher Fe bioavailability and that the underlying genetic regions controlling grain Fe levels do not co-localise with increased Fe absorption. Furthermore, we show that phytate levels do not correlate with Fe bioavailability in our wheat population and thus phytate-binding is insufficient to explain the lack of correlation between Fe bioavailability and Fe concentrations in the wheat grain. Finally, we observed no (Fe bioavailability) or low (Fe concentration) correlation between years for these traits, confirming that both are under strong environmental influence. Conclusions: This suggests that breeders will have to select not only for Fe levels directly in grains, but also increased bioavailability.
A retrospective comparative study of arthroscopic fixation for acute acromioclavicular joint dislocation: coracoid sling technique versus single-tunnel technique
Authors: Peng Liangquan , Zheng Yizi , Zhang Greg , Deng Zhenhan
Published: January 2021

Background

Arthroscopic fixation in acute acromioclavicular (AC) joint dislocation has become more popular and shown good clinical outcomes. This study aims to evaluate and compare the efficacy of single-tunnel technique (SST) and coracoid sling technique (CST) for the treatment of acute AC joint dislocation in order to provide more suitable treatment options and clinical recommendations for orthopaedic surgeons.
Methods

We retrospectively reviewed the charts of patients with acute Rockwood type IV and V AC joint dislocation who had undergone arthroscopic fixation procedure with SST or CST fixation between June 2009 and June 2018. A total of 90 consecutive patients identified from chart review were picked and divided into SST and CST groups, with 45 members in each group. The Visual Analog Scale (VAS) pain score, Constant shoulder functionality score, Karlsson AC joint score, the time of return to sports and activity, and plain radiographs of the affected shoulder at different time points of follow-up were all recorded for a minimum of 2 years postoperatively.
Results

The majority of the patients in both groups recovered to their preoperative activity levels with few complications. The average postoperative AC and coracoclavicular (CC) distances were significantly narrower than preoperative measurements in both groups, and no significant difference was observed between the two groups at 2 years post-op. The CST group had reduced operative time, shorter time of recovery of shoulder movements, higher Constant functionality scores and Karlsson AC joint scores, and fewer complications than the STT group at the last clinical follow-up.
Conclusions

CST technique achieved superior clinical outcomes with fewer complications compared to the traditional STT technique in arthroscopic treatment of acute AC joint dislocation. This technique could be considered as a reliable method for AC joint reconstruction.
Ultrasound Assessment of Twin Reversed Arterial Perfusion Sequence for the Prediction of Adverse Pregnancy Outcomes in the First Trimester
Authors: Tang Ying , Zeng Yan , Yang Taizhu , Yang Pan , Bao Shan , Luo Hong , Ying Junjie
Published: January 2021

ObjectivesTo investigate twin reversed arterial perfusion (TRAP) sequence for the prediction of TRAP-related adverse pregnancy outcomes at the gestational age of 11-14 weeks. MethodsPregnant women in the first trimester diagnosed with TRAP were recruited at West China Second University Hospital from January 2015 to June 2018. Systematic screening for the pump twin’s crown-rump length (CRL) and acardiac twin’s upper pole-rump length (URL) was conducted using ultrasonic detection. The (CRL-URL)/CRL and URL/CRL ratios were used to assess the pregnancy outcomes for the pump twin. ResultsTwenty-one pregnant women aged 21–39 years with a gestation of 11-14 weeks were recruited. TRAP was diagnosed on average (± standard deviation [SD]) at pregnancy week 13.1 ± 0.18. The pump twins’ mean (± SD) CRL was 6.65 ± 1.1 cm. The incidence of intrauterine death for the pump twins was 19.0% (n=4), the miscarriage rate was 14.3% (n=3), and the live birth rate was 66.7% (n=14). The (CRL-URL)/CRL ratios between the non-survival (intrauterine death and miscarriage) and survival groups significantly differed (0.33 ± 0.08 vs. 0.58 ± 0.08, p < 0.05). Similarly, the URL/CRL ratios between the non-survival and survival groups significantly differed (0.67 ± 0.08 vs. 0.42 ± 0.08, p < 0.05). ConclusionsThe (CRL-URL)/CRL and URL/CRL ratios were valuable indicators for determining pregnancy outcomes of pump twins with TRAP at an early gestational age.
Sclerotia Formation of Phlebopus Portentosus in Wild and Artificial Cultivation
Authors: Yang Tian-Wei , Liu Jing , Xu Xin-Jing , He Ming-Xia , Gao Feng , Fang Yi-Wei , Wang Wen-Bing , Dai Li-Ming , Wang Yun , Zhang Chun-Xia
Published: January 2021

Phlebopus portentosus is a favorite wild edible mushroom in the Xishuangbanna region, Yunnan, China and in northern Thailand. This bolete has a unique biotrophy. It can be saprobic but also form a tripartite association with root mealy bugs and plants. P. portentosus is the only edible fungus of Boletales in the world that can be cultivated artificially and anniversary produced at present. Sclerotium is often found at its natural environment and cultivated media, but the regularity and growth characteristics of the sclerotium are unknown. In this study the whole process of birth, growth, death and rebirth of the sclerotium of P. portentosus at the national and lab conditions was reported for the first time. The sclerotium formation in the nature is related to adversity, such as reduced rainfall and low temperature. The more rainfall, the less sclerotia. It seems that the lower temperature increased the sclerotium formation, however the relationship of the sclerotium formation to temperature was not obvious as the rainfall. Under artificial conditions the sclerotium formation of P. portentosus is related to the fungus physiological maturation, and the sclerotium occurrence always accompanied by appearance of the water drops on the colony. The result will set up a platform for research on importance of the sclerotium in life circle of P. portentosus.
Newborn Screening in Unselected Children Using Genomic Sequencing
Authors: Jian Min , Wang Xiaohong , Sui Yuanyuan , Fang Mingyan , Gao Ya , Guo Ruidong , Huang Yingping , Liu Chunhua , Feng Chenchen , Guan Yuanning , Gao Yuxiao , Wang Zhiwei , Li Shuli , Cheng Bochen , Sun Lina , Cui Fenghua , Guo Jia , Zhan Ying , Zhang Guohong , Zheng Ling , Su Fengxia , Xue Wei , Qian Puyi , Gao Shaobo , Chen Jiayu , Zhao Qian , Guan Lingyao , Lu Haorong , Nie Chao , Kristiansen Karsten , Hammarström Lennart , Jiang Xiaojing , Liu Junnian , Chen Fang
Published: January 2021

Background: The aim of this study is to investigate potentially curable or treatable medical conditions in unselected newborns using genomic sequencing(GS). Methods: 321 newborns from a cohort of pregnant women from Qingdao, China, underwent high-depth GS (average 47.42 fold), with the approval of the ethics committee. 61 Mendelian Diseases, 151 Primary Immunodeficiency Diseases(PID) and 5 DPWG recommeded Essential pharmacogenetic(PGx) genes were analyzed. Results: 121 Mendelian pathogenic or likely pathogenic variants associated with 31 inherited diseases were detected, among these hearing loss, congenital hypothyroidism, methylmalonic acidemia, methylmalonic acidemia with homocystinuria, phenylketonuria(PKU) and benign hyperphenylalaninemia accounted for half of the carrier variants. Three children with compound heterozygous variants at GJB2 and PAH were confirmed by Sanger sequencing. Follow-up of the three families confirmed that one child was diagnosed with PKU and two children with GJB2 variants were scheduled to undergo hearing loss testing every six months after genetic counceling due to the nature of incomplete penetrance of hearing loss. 11 heterozygous pathogenic/ likely pathogenic variants in eight PID genes were identified in 11 infants. All 321 newborns carried at least one variant at the five DPGW recommended PGx genes. Codeine and clopidogrel require more attention in giving prescription for 25% and 8% of newborns have a decreased function of CYP2D6 and CYP2C19 enzymes respectively. Conclusions: Our study is the largest to date using GS to sequence unselected newborns. The results suggest that using GS may be a suitable method for screening newborns for variants in a large number of disease associated genes.
Baseline Elevated Serum Angiopoietin-2 Predicts Long-Term Non-Regression of Liver Fibrosis After Direct-Acting Antiviral Therapy for Hepatitis C
Authors: Suda Goki , Kawagishi Naoki , Kimura Megumi , Maehara Osamu , Yamada Ren , Tokuchi Yoshimasa , Kubo Akinori , Kitagataya Takashi , Shigesawa Taku , Suzuki Kazuharu , Ohara Masatsugu , Nakai Masato , Sho Takuya , Natsuizaka Mitsuteru , Morikawa Kenichi , Ogawa Koji , Kudo Yusuke , Nishida Mutsumi , Sakamoto Naoya
Published: January 2021

We previously revealed that Angiopoietin-2 (Ang2) predicts non-regression of liver fibrosis based on liver stiffness measurement (LSM) at 24 weeks after anti-hepatitis C virus (HCV) treatment. In this study, we extended the observational period to 96 weeks to investigate the factors associated with non-regression after treatment with direct-acting-antivirals (DAAs). Patients treated with DAAs who underwent transient elastography at baseline and 24 and 96 weeks after DAA therapy were included. Baseline and post-treatment serum Ang2 levels were measured. Liver fibrosis stages were defined based on LSM. Multivariate regression was used to evaluate factors associated with non-regression of liver fibrosis between various time points. In total, 110 patients were included. Of these, 11% showed non-regression of LSM-based fibrosis stage at 96 weeks after DAA therapy. In multivariate analysis, advanced liver fibrosis stage and high baseline Ang2 levels were significantly associated with non-regression at 96 weeks. In patients with advanced liver fibrosis (F3/4), baseline Ang2 levels were associated with non-regression of liver fibrosis stage. Between SVR24 and SVR96, post-treatment Ang2 levels and controlled attenuation parameter values at SVR24 were significantly associated with non-regression of liver fibrosis stage in patients with F3/4. Thus, serum Ang2 levels are an important target for monitoring and therapy.
Our Choice Improves Use of Safer Conception Methods Among HIV Serodiscordant Couples in Uganda: A Cluster Randomized Controlled Trial Evaluating Two Implementation Approaches
Authors: Wagner Glenn , Wanyenze Rhoda , Beyeza-Kashesya Jolly , Gwokyalya Violet , Hurley Emily , Mindry Deborah , Finocchario-Kessler Sarah , Nanfuka Mastula , Tebeka Mahlet , Saya Uzaib , Booth Marika , Ghosh-Dastidar Bonnie , Linnemayr Sebastian , Staggs Vincent , Goggin Kathy
Published: January 2021

Background: Safer conception counseling (SCC) to promote safer conception methods (SCM) is not yet part of routine family planning or HIV care, and to date there are no published controlled evaluations of SCC.Methods: In a hybrid, cluster randomized controlled trial, six HIV clinics were randomly assigned to implement the SCC intervention Our Choice using either a high (SCC1) or low intensity (SCC2) approach, or existing family planning services (usual care). 389 HIV clients considering childbearing with an HIV-negative partner enrolled. The primary outcome was self-reported use of appropriate reproductive method (SCM if trying to conceive; modern contraceptives if not) over 12 months or until pregnancy. Results: The combined intervention groups used appropriate reproductive methods more than usual care [20.8% vs. 6.9%; adjusted OR (95% CI)=10.63 (2.79, 40.49)], and SCC1 reported a higher rate than SCC2 [27.1% vs. 14.6%; OR (95% CI)=4.50 (1.44, 14.01)]. Among those trying to conceive, the intervention arms reported greater accurate use of SCM compared to usual care [24.1% vs. 0%; OR (95% CI)=91.84 (4.94, 1709.0)], and SCC1 performed better than SCC2 [34.6% vs. 11.5%; OR (95% CI)=6.43 (1.90, 21.73)]; the arms did not vary on modern contraception use among those not trying to conceive. A cost of $631 per person was estimated to obtain accurate use of SCM in SCC1, compared to $1014 in SCC2. Conclusions: More intensive training and supervision leads to greater adoption of complex SCM behaviors and is more cost-effective than the standard implementation approach.Trial registration: Clinicaltrials.gov, NCT03167879; date registered May 23, 2017; https://clinicaltrials.gov/ct2/show/NCT03167879.
Effect of Supplementation Yeast Fermentation Products on Growth Performance and Intestinal Health of Weaned Piglets Challenged With Salmonella Typhimurium
Authors: Zhao Yongsen , Wang Danping , Jiang Meng , Chen Jinglong , Yang Xiaojing
Published: January 2021

Background: This study investigated the effects of piglets with dietary supplementation yeast fermentation product (YFP) on growth performance, immune status and intestinal inflammation after a Salmonella typhimurium challenge. Twenty-four weaned piglets were assigned to four treatments including: non-challenge control (Con); Salmonella typhimurium-challenged control (ST); ST + 0.2% YFP (0.2% YFP); and ST + 0.4% YFP (0.4% YFP). All piglets were challenged twice with Salmonella typhimurium. All of them were killed at 7th day after the second challenge to obtain plasma and intestine for analysis.Results: 0.4% YFP increased average daily gain (ADG) and duodenal villus height and villus height/ crypt depth (P < 0.05) and decreased feed-gain ratio (P < 0.05) after Salmonella typhimurium challenge compared with ST group. The 0.4% YFP decreased the elevating concentrations IL-1b and IL-6 (P < 0.01) induced by Salmonella typhimurium and increased the concentration of IL-10 (P < 0.05) in plasma compared with ST group. Furthermore, YFP influenced the apoptosis related mRNA levels of Bax, Bcl-2 and caspase 3 (P < 0.05) and increased intestinal occludin protein expression (P < 0.05). 0.4% YFP down-regulated the mRNA expressions of TLR4, MyD88, IRAK1, TRAF6 and NFkB (P < 0.05) and decreased the mRNA expression of IL-6, TNFa (P < 0.05) and increased the IL-10 (P < 0.01) in duodenum compared with ST group. In addition, 0.4% YFP decreased the phosphorylation levels of p38 MAPK and ERK1/2 (P < 0.01).Conclusions: Dietary 0.4% yeast fermentation product supplementation had positive effects on growth performance and intestinal barrier function and reduced intestinal inflammation of weaned piglets challenged with Salmonella typhimurium.
CHOP Deletion and Anti-Neuroinflammation Treatment With Hesperidin Synergistically Attenuate NMDA Retinal Injury in Mice
Authors: Sato Kota , Sato Taimu , Ohno-Oishi Michiko , Ozawa Mikako , Maekawa Shigeto , Shiga Yukihiro , Yabana Takeshi , Yasuda Masayuki , Himori Noriko , Omodaka Kazuko , Fujita Kosuke , Nishiguchi Koji M , Nakazawa Toru
Published: January 2021

Background: Glaucoma is a leading cause of blindness worldwide and is characterized by degeneration associated with the death of retinal ganglion cells (RGCs). It is believed that glaucoma is a group of heterogeneous diseases with multifactorial pathomechanisms. Here, we investigate whether anti-inflammation treatment with an ER stress blockade can selectively promote neuroprotection against NMDA injury in the RGCs.Methods: Retinal excitotoxicity was induced with an intravitreal NMDA injection. Microglial activation and neuroinflammation were evaluated with Iba1 immunostaining and cytokine gene expression. A stable HT22 cell line transfected with an NF-kB reporter was used to assess NF-kB activity after hesperidin treatment. CHOP-deficient mice were used as a model of ER stress blockade. Retinal cell death was evaluated with a TUNEL assay.Results: In the NMDA injury group, Iba1-positive microglia increased 6 h after NMDA injection. Also at 6 h, pro-inflammatory cytokines and chemokines increased, including TNFα, IL-1b, IL-6 and MCP-1. In addition, the MCP-1 promoter-driven EGFP signal, which we previously identified as a stress signal in injured RGCs, also increased; hesperidin treatment suppressed this inflammatory response and reduced stressed RGCs. In CHOP-deficient mice that received an NMDA injection, the gene expression of pro-inflammatory cytokines, chemokines, markers of active microglia, and inflammatory regulators was greater than in WT mice. In WT mice, hesperidin treatment partially prevented retinal cell death after NMDA injury; this neuroprotective effect was enhanced in CHOP-deficient mice.Conclusions: These findings demonstrate that ER stress blockade is not enough by itself to prevent RGC loss due to neuroinflammation in the retina, but it has a synergistic neuroprotective effect after NMDA injury when combined with an anti-inflammatory treatment based on hesperidin.
Feeding Experiments on Vittina Turrita (Mollusca, Gastropoda, Neritidae) Reveal Tooth Contact Areas and Bent Radular Shape During Foraging
Authors: KRINGS WENCKE , HEMPEL CHRISTINE , SIEMERS LISA , NEIBER MARCO , GORB STANISLAV
Published: January 2021

The radula is the food gathering and processing structure and one important autapomorphy of the Mollusca. It is composed of a chitinous membrane with small, embedded teeth representing the interface between the organism and its ingesta. In the past, various approaches aimed at connecting the tooth shapes, which are highly distinct within single radulae due to their different functions. However, conclusions from the literature have been mainly drawn from microscopical analyses of mounted radulae, but the real interacting radular parts – even though the precise contact areas are essential for determining a tools functionality – and the 3D architecture of this complex feeding structure have not been previously determined. In the experimental approach presented here individuals of Vittina turrita (Neritidae, Gastropoda) were fed with algae paste attached to different sandpaper types. By comparison with radulae from a control group, sandpaper-induced tooth wear patterns were identified and both the area and volume loss were quantified. In addition to the exact contact area of each tooth, conclusions about the 3D position of teeth and the radular bending during feeding motion could be drawn. Furthermore, hypotheses about the specific functions of individual tooth types could be put forward. This kind of feeding experiments under controlled conditions is new for Mollusca and may provide a good basis for future studies on the radula functional morphology. It can be potentially applied to species with distinct tooth morphologies and ecological niches.
Role of 18F-PET-CT to Predict Pathological Response After Neoadjuvant Treatment of Rectal Cancer
Authors: Caruso Riccardo , Vicente Emilio , Quijano Yolanda , Duran Hipolito , Fabra Isabel , Diaz Eduardo , Malave Luis , Agresott Ruben , Cañamaque Lina Garcia , Ielpo Benedetto , Ferri Valentina
Published: January 2021

Objectives: Neoadjuvant radiochemotherapy (nCRT) is universally considered to be a valid treatment to achieve downstaging, improve local disease control and obtain better resectability in locally advanced rectal cancer (LARC). The aim of this study is to correlate the change in tumor 18F -FDG PET-CT standardized uptake value (SUV) before and after nCRT, in order to obtain an early prediction of pathologic response (pR) achieved in patients with LARC.Data description: We performed a retrospective analysis of patients with LARC diagnosis who underwent curative resection. All patients received nCRT and surgical treatment was carried after 8/12th. All patients underwent a baseline 18F -FDG PET-CT scan within the week prior to the initiation of the treatment (PET-CT SUV1) and a second scan (PET-C T SUV2) within six weeks of the completion of nCRT. Furthermore, we evaluated the prognostic value of 18F -FDG PET-CT in terms of disease free survival (DFS) and overall survival (OS) in patients with LARC.A total of 133 patients with LARC were included in the study. Patients were divided in two groups according to the TRG (tumor regression grade): 107 (80%) as Responders group (TRG0-TRG1) and 26 (25%) as the No-Responders group (TRG2-TRG3). We obtained a significant difference in Δ%SUV between the two different groups responders vs no responders (p<0.012).The results of this analysis have shown that 18F-FDG PET-CT may be an indicator in order to evaluate the pR to nCRT in patients with LARC. The decrease in 18F-FDG PET-CT uptake in the primary tumor may offer primary information in order to early identify those patients more likely to obtain a pCR to nCRT and predict those unlikely to regress significantly.
Effect of Antibiotic-induced Intestinal Dysbacteriosis on Bronchopulmonary Dysplasia and Related Mechanisms
Authors: Ran Xiao , He Yu , Ai Qing , Shi Yuan
Published: January 2021

BackgroundThe modification of the gut microbiota by antibiotics may influence the disease susceptibility and immunological responses. Infants in the neonatal intensive care unit (NICU) subjected to frequent antibiotics and oxygen therapies, which may give rise to the local and systemic inflammatory reactions and progression of bronchopulmonary dysplasia (BPD). This study aimed to investigate the role of intestinal dysbacteriosis by antibiotic therapy before hyperoxia exposure in the progression of BPD.MethodsMice had been exposed to hyperoxia (85% O2) since postnatal day 3 until day 16 for the BPD model establishment, treated with antibiotics from postnatal day 2 until day 8. Treated mice and appropriate controls were harvested on postnatal day 10 for 16S rRNA gene sequencing, or postnatal day 17 for assessment of alveolar morphometry and macrophages differentiation.ResultsAntibiotic-induced intestinal dysbacteriosis before hyperoxia exposure gave rise to deterioration of BPD evidenced by reduced survival rates and alveolarization, moreover, antibiotic-induced intestinal dysbacteriosis resulted in increased iNOS and decreased Arg-1 levels in lung homogenates.ConclusionBroad-spectrum antibiotic-induced intestinal dysbacteriosis may participate in BPD pathogenesis via alteration of the macrophage polarization status. Manipulating the gut microbiota may potentially intervene the therapy of BPD.
An update on the distribution of Glossina (tsetse flies) at the wildlife-human-livestock interface of Akagera National Park, Rwanda
Authors: Gashururu Richard S. , Githigia Samuel M. , Gasana Methode N , Habimana Richard , Maingi Ndichu , Cecchi Giuliano , Paone Massimo , Zhao Weining , Masiga Daniel K. , Gashumba James
Published: January 2021

BackgroundGlossina (Tsetse flies) biologically transmit trypanosomes that infect both humans and animals. Knowledge of their distribution patterns is a key element to better understand the transmission dynamics of trypanosomosis. Tsetse distribution in Rwanda has not been well enough documented and little is known of their current distribution. This study determined the current spatial distribution, abundance, diversity, and seasonal variations of tsetse flies in and around the Akagera National Park.MethodsA longitudinal stratified sampling, following the seasons was used. Biconical traps were deployed in 55 sites for six consecutive days of each study month from May 2018 to June 2019, and emptied every 48hours. Flies were identified using FAO keys and the number of flies per trap day (FTD) was used to determine the apparent density. Pearson chi-square (χ2) and parametrical tests (t-test and ANOVA) were used to determine the variations between the variables. The significance (p< 0.05) at 95% confidence interval was considered. Logistic regression was used to determine the association between tsetse occurrence and the associated predictors. Results39,516 tsetse flies were collected, of which 73.4% and 26.6% were from inside Akagera NP and the interface area respectively. Female flies accounted for 61.3% while 38.7% were males. Two species were identified, i.e. G. pallidipes [n=29,121, 7.4 flies/trap/day (FTD)] and G. morsitans centralis (n=10,395; 2.6 FTD). The statistical difference in numbers was significant between the two species (p=0.000). The flies were more abundant during the wet season (15.8 FTD) than the dry season (4.2 FTD). Large numbers of flies were trapped around the swamp areas (69.1 FTD) inside the park and in Nyagatare District (11.2 FTD) at the interface. Glossina morsitans was 0.218 times less likely to occur outside the park. The chance of co-existing between the two species reduced outside the protected area (0.021 times).ConclusionsThe occurrence of Glossina seems to be limited to the protected Akagera NP and a narrow band in its surroundings. This finding will be crucial to design appropriate control strategies. Glossina pallidipes was found in higher numbers and therefore conceivably the most important vector of trypanosomosis. Regional coordinated control and regular monitoring of Glossina distribution are recommended.
Establishment And Validation Of Coagulation Factor-based Nomogram For Predicting The Recurrence-free Survival Of Prostate Cancer
Authors: Meng Jialin , Bian Zichen , Zhu Chenyu , Tao Zhi , Jin Xiaoyan , Zhou Jun , Zhang Meng , Liang Chaozhao
Published: January 2021

Background: We aimed to establish and validate a coagulation-feature-based nomogram to predict recurrence-free survival for prostate cancer patients.Methods: The study contained 168 prostate cancer patients who had received radical prostatectomy between 2012 and 2018. The Kaplan-Meier plot and log-rank analysis were used to screen recurrence-free survival-related features. The nomogram was established by combining the significant coagulation features with clinicopathological characteristics by using Cox regression analysis. The accuracy and clinical significance of the nomogram model were assessed by receiver operating characteristic (ROC) curve, Kaplan-Meier plot, and calibration plot. Besides, we explored the correlation between coagulation pathway activity and patients’ prognosis based on public datasets by using gene set variation analysis (GSVA) analysis.Results: The results suggested that patients in the high-risk subgroup showed unfavorable prognoses than those in the low-risk subgroup classified by the nomogram model in both the training (log-rank P < 0.0001) and validation (log-rank P = 0.0004) cohorts. The nomogram model exhibited high discriminative accuracy in the training cohort [1-year area under the curve (AUC) of 0.74, and 3-year AUC of 0.69], which was confirmed in the internal validation cohort (C-index = 0.651). Besides, the calibration plots confirmed good concordance for the prediction of recurrence-free survival at 1 and 3 years. Besides, the subgroup analyses confirmed the usage of this model in different clinicopathological subgroups. Finally, GSVA analyses suggested that patients with higher coagulation pathway scores mostly had unfavorable prognoses than those with lower scores, a result consistent with the findings obtained above.Conclusions: In conclusion, we develop a practical nomogram model for the recurrence-free survival predicting of prostate cancer patients. This model may offer clinicians prognostic assessments and facilitate personalized treatment.
Identification of Fanconi Anemia Pathway Genes as Novel Prognostic Biomarkers and Therapeutic Targets for Breast Cancer
Authors: Lin Hongsheng , Xie Yangyi , Pan Aiping , Wei Wei , Diao Limei , Yang Li , Kong Yinzhi , Li Mingfen
Published: January 2021

BackgroundGlobally, breast cancer is one of the most common cancers with poor prognosis. The Fanconi anemia (FA) pathway genes maintain genome stability and play important roles in human diseases, including cancer. However, the prognostic values and biological roles of FA pathway genes in breast cancer have not been clarified.MethodsIn this study, the ONCOMINE, UCSC Xena, UALCAN, Kaplan-Meier plotter, cBioPortal, GEPIA, GeneMANIA, DAVID and TIMER databases were used to investigate the transcriptional and survival data of FA pathway genes in patients with breast cancer.ResultsMost of the FA pathway genes were found to be significantly upregulated in breast cancer tissues when compared to normal tissues. Additionally, the elevated expression levels of FA pathway genes were significantly associated with poor survival outcomes in breast cancer patients. Through functional enrichment analysis, the FA pathway genes were positively associated with cell cycle and nucleoplasm and negatively correlated with SRP-dependent co-translational protein targeting to membrane and ribosome. Furthermore, the expression levels of FA pathway genes exhibited a significant positive association with immune infiltration.ConclusionThe FA pathway genes are potential prognostic biomarkers for breast cancer and may offer effective as well as new strategies for cancer management.
Genetic Association of rs15672 and rs12640056 Polymorphisms with the Susceptibility of Systemic Lupus Erythematosus in a Chinese Population
Authors: Zhang Naidan , Zhai Jianzhao , Zhang Ping , Zhang Junlong , Cai Bei , Luo Yubin , Wu Yongkang
Published: January 2021

In this study, we aimed to investigate the relationship of IKBKE rs15672 and BANK1 rs12640056 gene polymorphisms with systemic lupus erythematosus (SLE) susceptibility in China. A case-control study was performed on 567 SLE patients and 345 healthy controls. Six single nucleotide polymorphisms (rs15672, rs2296164, rs12640056, rs6842661, rs1957106 and rs2274064) and clinical features were analyzed. Genotyping was executed with improved multiplex ligation detection reaction assay. SNP rs15672 increased the risk (P = 0.028, OR = 1.25, 95%CI = 1.02–1.52) but rs12640056 decreased the risk of SLE (P = 0.015, OR = 0.78, 95%CI = 0.64–0.95). For rs15672, patients carrying allele A assumed high-level IL-6 (25.36 ± 4.64 vs 16.56 ± 2.95, P = 0.036) and IL-4 (12.06 ± 4.51 vs 4.88 ± 1.76, P = 0.047), but low-level granzyme B (14.07 ± 1.86 vs 18.38 ± 3.85, P = 0.023), IL-18 (267.39 ± 14.67 vs 348.57 ± 44.25, P = 0.002) and IL-33 (0.91 ± 0.26 vs 2.19 ± 1.35, P = 0.029). Organ injury showed that mutant genotype at rs15672 had high-prevalence of arthritis (32.02%) and serositis (34.78%), but low in neuropathy (9.09%). For rs12640056, patients carrying allele T assumed low-level IL-33 (0.46 ± 0.17 vs 2.16 ± 1.00, P = 0.009). In conclusion, gene polymorphisms of rs15672 and rs12640056 present relevant with susceptibility of SLE, and affect the expression of cytokine and organ injury.
Risk of Major Bleeding by Ethnicity and Socioeconomic Deprivation among 488,107 People in Primary Care: A Cohort Study
Authors: Tse Wai Chung , Grey Corina , Harwood Matire , Jackson Rod , Kerr Andrew , Poppe Katrina , Mehta Suneela , Pylypchuk Romana , Wells Sue , Selak Vanessa
Published: January 2021

Background: Antithrombotic medications (antiplatelets and anticoagulants) reduce the risk of cardiovascular disease (CVD), but with the disadvantage of increasing bleeding risk. Ethnicity and socioeconomic deprivation are independent predictors of major bleeds among patients without CVD, but it is unclear whether they are also predictors of major bleeds among patients with CVD or atrial fibrillation (AF) after adjustment for clinical variables. Methods: Prospective cohort study of 488,107 people in New Zealand Primary Care (including 64,420 Māori, the indigenous people of New Zealand) aged 30-79 years who had their CVD risk assessed between 2007 and 2016. Participants were divided into three mutually exclusive subgroups: (1) AF with or without CVD (n=15,212), (2) CVD and no AF (n=43,790), (3) no CVD or AF (n=429,105). Adjusted hazards ratios (adjHRs) were estimated from Cox proportional hazards models predicting major bleeding risk for each of the three subgroups to determine whether ethnicity and socioeconomic deprivation are independent predictors of major bleeds in different cardiovascular risk groups. Results: In all three subgroups (AF, CVD, no CVD/AF), Māori (adjHR 1.63 [1.39-1.91], 1.24 [1.09-1.42], 1.57 [95% CI 1.45-1.70], respectively), Pacific people (adjHR 1.90 [1.58-2.28], 1.30 [1.12-1.51], 1.62 [95% CI 1.49-1.75], respectively) and Chinese people (adjHR 1.53 [1.08-2.16], 1.15 [0.90-1.47], 1.13 [95% CI 1.01-1.26], respectively) were at increased risk of a major bleed compared to Europeans, although for Chinese people the effect did not reach statistical significance in the CVD subgroup. Compared to Europeans, Māori and Pacific peoples were generally at increased risk of all bleed types (gastrointestinal, intracranial and other bleeds). An increased risk of intracranial bleeds was observed among Chinese and Other Asian people and, in the CVD and no CVD/AF subgroups, among Indian people. Increasing socioeconomic deprivation was also associated with increased risk of a major bleed in all three subgroups (adjHR 1.07 [95% CI 1.02-1.12, 1.07 [1.03-1.10], 1.10 [1.08-1.12], respectively, for each increase in socioeconomic deprivation quintile). Conclusion: Ethnicity and socioeconomic status should be considered in bleeding risk assessments to guide the use of antithrombotic medication for the management of AF and CVD. Primary Funding Source: The Health Research Council of New Zealand
A Twins Case of Lissencephaly With GPR56 Compound Heterozygous Mutations and Literatures Review
Authors: Lin Wenxin , Chai Yingying , Zhang Xia , Huang Tingting , Zheng Guo , Zhang Gang , Peng Fang , Huang Yanjun
Published: January 2021

Background: Lissencephaly (LIS) is a malformation of cortical development characterized by developmental delay and seizure in combination with wide gyrus, superficial sulcus, and thickened cortex. Up to date, 20 genes have been implicated in LIS. However, GRP56-related LIS has never been reported, which was considered one causative gene for bilateral frontoparietal polymicrogyria(BFPP). Methods: Genetic testing of the proband was performed by whole exome sequencing and mainly analyzed 662 genes related to brain hypoplasia, white matter abnormalities, and hypothalamic-pituitary axis abnormalities such us AAAS, AARS2, ABAT, ABCC8, etc.. And the candidate mutations were further confirmed by polymerase chain reaction (PCR) and Sanger sequencing. Though we did genetic testing on the twin sisters and their parents, we could only obtain the clinical data of the older sister.Results: We reported a case of LIS twins, form a nonconsanguineous family, both carried the novel compound heterozygous GPR56 mutations, p.F76fs and p.H607fs.The older sister manifested lissencephaly, seizures, and flathead deformity and the younger sister had lissencephaly. We summarized their clinical characteristics and reviewed all the literatures of LIS and GPR56 to further clarify the correlation between genotype and phenotype.Conclusion: The LIS twins with GPR56 mutations were the first reported. By reviewing the clinical manifestations of LIS and GPR56 mutations, we validated the association between them, and broaden the clinical manifestations of GPR56 related phenotypes, indicating the importance of GPR56 screening in LIS patients.
Etoposide as an Effective Drug for Adult Macrophage Activation Syndrome: A Retrospective Study
Authors: He Lingbo , Jin Zhili , Liu Menghan , Cui Tingting , Wu Lin , Wang Zhao , Wang Yini
Published: January 2021

BackgroundAutoimmune disease related hemophagocytic syndrome, in other words, macrophage activation syndrome(MAS), is a rare, but lethal complication of autoimmune disease. At present, specific treatment guidelines for adult MAS have not been formulated, most experience are derived from children, researches about etoposide are scarce. As the importance of etoposide in the initial treatment had been proved in other subtypes of hemophagocytic syndrome, the objective of this study is to investigate the effectiveness of etoposide in the treatment of the adult macrophage activation syndrome.Result74 patients with autoimmune disease related hemophagocytic syndrome were involved in this study, they were divided into two groups based on initial treatment, group 1(n=53): initial therapy did not contain etoposide, group 2(n=21): initial therapy contained etoposide. The overall response rate and complete response rate of group 2 were significantly higher than group 1(ORR 90.5% vs 24.5%, CRR 33.3% vs 3.8%, P<0.05). Patients with different HLH remission states have significantly different prognosis(P<0.001).ConclusionAdopting VP-16 in initial treatment can significantly increase the OR rate and CR rate of adult MAS patients, and the HLH states influenced the prognosis significantly.
Characteristics and Clinical Course of Adult in-Patients With SARS-CoV-2 Pneumonia in Bogotá, Colombia.
Authors: Galindo Javier Leonardo , Lutz Juan Ricardo , Izquierdo María Alejandra , Parra Katherine , Prieto Lina María , Carrillo Jorge Alberto
Published: January 2021

Background: SARS-CoV-2 virus has spread worldwide causing a crisis in healthcare systems. We aimed to describe the clinical characteristics and to explore risk factors of death, critical care admission and use of invasive mechanical ventilation in hospitalized patients with SARS-CoV-2 pneumonia in Bogotá, Colombia.Methods: We conducted a cross-sectional study of adult patients with laboratory-confirmed SARS-CoV-2 pneumonia. Demographic, clinical, and treatment data were extracted from electronic records. Univariate and multivariable methods were performed to investigate the relationship between each variable and clinical outcomes at 28 days of follow-up.Results: Between March 20 and June 30, 2020, 377 adults (56.8% male) were included in the study, of whom 85 (22.6%) died. Non-survivors were older on average than survivors (mean age, 56.7 years [SD 15.8] vs. 70.1 years [SD 13.9]) and more likely male (28 [32.9%] vs. 57 [67.1%]). Most patients had at least one underlying disease (333 [88.3%]), including arterial hypertension (149 [39.5%]), overweight (145 [38.5%]), obesity (114 [30.2%]) and diabetes mellitus (82 [21.8%]). Frequency of critical care admission (158 [41.9%]) and invasive mechanical ventilation (123 [32.6%]) was high. Age over 65 years (OR 9.26, 95% CI 3.29-26.01; p=0.00), ICU admission (OR 12.37, 95% CI 6.08-25.18; p=0.00), and arterial pH higher than 7.47 (OR 0.25, 95% CI 0.08-0.74; p=0.01) were independently associated with in-hospital mortality.Conclusions: In this study of in-hospital patients with SARS-CoV-2 pneumonia frequency of death was similar to what has been reported. ICU admission and use of invasive mechanical ventilation was high. Risk factors as older age, ICU admission, and arterial pH were associated with mortality.
Characteristics and Clinical Course of Adult in-Patients With SARS-CoV-2 Pneumonia in Bogotá, Colombia.
Authors: Galindo Javier Leonardo , Lutz Juan Ricardo , Izquierdo María Alejandra , Parra Katherine , Prieto Lina María , Carrillo Jorge Alberto
Published: January 2021

Background: SARS-CoV-2 virus has spread worldwide causing a crisis in healthcare systems. We aimed to describe the clinical characteristics and to explore risk factors of death, critical care admission and use of invasive mechanical ventilation in hospitalized patients with SARS-CoV-2 pneumonia in Bogotá, Colombia.Methods: We conducted a cross-sectional study of adult patients with laboratory-confirmed SARS-CoV-2 pneumonia. Demographic and clinical data were extracted from electronic records. Univariate and multivariable methods were performed to investigate the relationship between each variable and clinical outcomes at 28 days of follow-up.Results: Between March 20 and June 30, 2020, 377 adults (56.8% male) were included in the study, of whom 85 (22.6%) died. Non-survivors were older on average than survivors (mean age, 56.7 years [SD 15.8] vs. 70.1 years [SD 13.9]) and more likely male (28 [32.9%] vs. 57 [67.1%]). Most patients had at least one underlying disease (333 [88.3%]), including arterial hypertension (149 [39.5%]), overweight (145 [38.5%]) and obesity (114 [30.2%]). Critical care admission (158 [41.9%]) and invasive mechanical ventilation (123 [32.6%]) was high. Age over 65 years (OR 9.26, 95% CI 3.29-26.01; p=0.00), ICU admission (OR 12.37, 95% CI 6.08-25.18; p=0.00), and arterial pH higher than 7.47 (OR 0.25, 95% CI 0.08-0.74; p=0.01) were associated with in-hospital mortality.Conclusions: In this study of in-hospital patients with SARS-CoV-2 pneumonia frequency of death was similar to what has been reported. ICU admission and use of invasive mechanical ventilation was high. Risk factors as older age, ICU admission, and arterial pH were associated with mortality.
Risk factors for persistent abnormality on chest radiographs at 12-weeks post hospitalisation with PCR confirmed COVID-19
Authors: Wallis Tim JM , Heiden Emily , Horno Jose , Welham Ben , Burke Hannah , Freeman Anna , Dexter Lee , Fazleen Aishath , Kong Alex , McQuitty Christopher , Watson Mark , Poole Stephen , Brendish Nathan J , Clark Tristan W , Wilkinson Thomas MA , Jones Mark G , Marshall Ben G
Published: January 2021

BackgroundThe long-term consequences of COVID-19 remain unclear. There is concern a proportion of patients will progress to develop pulmonary fibrosis. We aimed to assess the temporal change in CXR infiltrates in a cohort of patients following hospitalisation for COVID-19.MethodsWe conducted a single-centre prospective cohort study of patients admitted to University Hospital Southampton with confirmed SARS-CoV2 infection between 20th March – 3rd June 2020. Patients were approached for standard-of-care follow-up 12-weeks after hospitalisation. Inpatient and follow-up CXRs were scored by the assessing clinician for extent of pulmonary infiltrates; 0-4 per lung (Nil=0, <25%=1, 25-50%=2, 51-75%=3, >75%=4). Results 101 patients with paired CXRs were included. Demographics: 53% male with a median (IQR) age 53.0 (45-63) years and length of stay 9 (5-17.5) days. The median CXR follow-up interval was 82 (77-86) days with median baseline and follow-up CXR scores of 4.0 (3-5) and 0.0 (0-1) respectively. 32% of patients had persistent CXR abnormality at 12-weeks. In multivariate analysis length of stay (LOS), smoking-status and obesity were identified as independent risk factors for persistent CXR abnormality. Serum LDH was significantly higher at baseline and at follow-up in patients with CXR abnormalities compared to those with resolution. A 5-point composite risk score (1-point each; LOS≥15 days, Level 2/3 admission, LDH>750 U/L, obesity and smoking-status) strongly predicted risk of persistent radiograph abnormality (0.81).ConclusionPersistent CXR abnormality 12-weeks post COVID-19 was common in this cohort. LOS, obesity, increased serum LDH, and smoking-status were risk factors for radiograph abnormality. These findings require further prospective validation.
Development and Validation of Teacher and Student Questionnaires Measuring Inhibitors of Curriculum Viability
Authors: Khan Rehan Ahmed , Spruijt Annemarie , Mahboob Usman , Eraky Mohamed Al , Merrienboer Jeroen J. G. van
Published: January 2021

BackgroundCurriculum viability is determined by the degree to which quality standards have or have not been met, and by the inhibitors that affect attainment of those standards. The literature reports many ways to evaluate whether a curriculum reaches its quality standards, but less attention is paid to the identification of viability inhibitors in different areas of the curriculum that hamper the attainment of quality. The purpose of this study is to develop and establish the reliability and validity of questionnaires that measure the presence of inhibitors in an undergraduate medical curriculum. MethodsTeacher and student questionnaires developed by the authors were sent to medical educationalists for qualitative expert validation and to establish their content validity. To establish the response process validity, cognitive interviews were held with teachers and students to clarify any confusion about the meaning of items in the questionnaires. Reliability and construct validity of the questionnaires were established by responses from 575 teachers and 247 final-year medical students.Results Qualitative expert validation was provided by 21 experts. The initial teacher and student questionnaires containing respectively 62 items to measure 12 theoretical constructs, and 28 items to measure 7 constructs, were modified to improve their clarity and relevance. The overall scale validity index for the questionnaires was, in order, .95 and .94. Following the cognitive interviews, the resultant teacher and student questionnaires were reduced to respectively 52 and 23 items. Furthermore, after the confirmatory analysis, the final version of the teacher questionnaire was reduced to 25 items to measure 6 constructs and the student questionnaire was reduced to 14 items to measure 3 constructs. Good-for-fit indices were established for the final model and Cronbach alphas of, in order, .89 and .81 were found for the teacher and student questionnaire.ConclusionThe valid and reliable curriculum viability inhibitor questionnaires for teachers and students developed in this study can be used by medical schools to identify inhibitors to achieve standards in different areas of the curriculum.
Large Rhizosphere Bacterial Diversity Exits Among Wild Progenitor Species of Modern Sugarcane (Saccharum Spp. Inter-Specific Hybrids)
Authors: Malviya Mukesh Kumar , Li Chnag-Ning , Solanki Manoj Kumar , Lakshmanan Prakash , Singh Rajesh Kumar , Verma Krishan K , Singh Pratiksha , sharma Anjney , Song Qi-Qi , Nong Qian , Song Xiu-Peng , Li Yang-Rui
Published: January 2021

BackgroundRhizosphere is rich in highly diverse and complex microbial communities. Plant growth promoting rhizpbacteria and diazotrops are played crucial role in plant growth and development. In this study, rhizosphere soils were collected from five wild Saccharum species- S. officinarum L. cv Badila (BRS), S. barberi Jesw. cv Pansahi (PRS), S. robustum (RRS), S. spontaneum (SRS), and S. sinense Roxb. cv Uba (URS) for studied of rhizosphere and diazotroph bacterial diversity using 16S rRNA and nifH gene amplification and sequencing.ResultsWe detected a total of 6202 operational taxonomic units (OTUs) specific to the bacterial communities from all species combined. Out of the 107 bacterial communities detected among all samples, we found a core microbiome of 31 rhizobacterial families spread across all the species analyzed. A total of 1099 OTUs were identified for diazotrophs with a core microbiome of 9 families distributed among all the sugarcane species. The core microbiomes were distributed across twenty genera-Bradyrhizobium, Dechloromonas, Desulfovibrio, Stenotrophomonas, Xanthobacter, Anaeromyxobacter, Azospirillum, Pseudoacidovorax, Methylobacterium, Azoarcus, Paenibacillus, Ideonella, Beijerinckia, Paraburkholderia, Burkholderia, Ruficoccus, Geobacter, Sinorhizobium, Kosakonia, and Azotobacter. ConclusionThe results presented here advance our understanding of rhizosphere associated bacterial diversity among genetically closely related wild species and provide a knowledge base for studying the evolution of rhizobacteria-host plant association during crop domestication.