bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of PCR assays to specifically detect and identify 37 Lactobacillus species in a single 96 well plate
Authors: Kim Eiseul , Yang Seung-Min , Lim Bora , Park Si Hong , Rackerby Bryna , Kim Hae-Yeong
Published: April 2020

Background

Lactobacillus species are used as probiotics and play an important role in fermented food production. However, use of 16S rRNA gene sequences as standard markers for the differentiation of Lactobacillus species offers a very limited scope, as several species of Lactobacillus share similar 16S rRNA gene sequences. In this study, we developed a rapid and accurate method based on comparative genomic analysis for the identification of 37 Lactobacillus species that are commonly used in probiotics and fermented foods.

Results

To select species-specific sequences or genes, a total of 180 Lactobacillus genome sequences were compared using Python scripts. In 14 out of 37 species, species-specific sequences could not be found due to the similarity of the 16S–23S rRNA gene. Selected unique genes were obtained using comparative genomic analysis and all genes were confirmed to be specific for 52,478,804 genomes via in silico analysis; they were found not to be strain-specific, but to exist in all strains of the same species. Species-specific primer pairs were designed from the selected 16S–23S rRNA gene sequences or unique genes of species. The specificity of the species-specific primer pairs was confirmed using reference strains, and the accuracy and efficiency of the polymerase chain reaction (PCR) with the standard curve were confirmed. The PCR method developed in this study is able to accurately differentiate species that were not distinguishable using the 16S rRNA gene alone. This PCR assays were designed to detect and identify 37 Lactobacillus species. The developed method was then applied in the monitoring of 19 probiotics and 12 dairy products. The applied tests confirmed that the species detected in 17 products matched those indicated on their labels, whereas the remaining products contained species other than those appearing on the label.

Conclusions

The method developed in this study is able to rapidly and accurately distinguish different species of Lactobacillus, and can be used to monitor specific Lactobacillus species in foods such as probiotics and dairy products.
Wide crossing diversify mitogenomes of rice
Authors: Yang Weilong , Zou Jianing , Wang Jiajia , Li Nengwu , Luo Xiaoyun , Jiang Xiaofen , Li Shaoqing
Published: April 2020

Background

In most angiosperms, the inheritance of the mitochondria takes place in a typical maternal manner. However, very less information is available about if the existence of structural variations or not in mitochondrial genomes (mitogenomes) between maternal parents and their progenies.

Results

In order to find the answer, a stable rice backcross inbred line (BIL) population was derived from the crosses ofOryza glaberrima/Oryza sativa//Oryza sativa.The current study presents a comparative analysis of the mitogenomes between maternal parents and five BILs. There were recorded universal structural variations such as reversal, translocation, fusion, and fission among the BILs. The repeat-mediated recombination and non-homologous end-joining contributed virtually equal to the rearrangement of mitogenomes. Similarly, the relative order, copy-number, expression level, and RNA-editing rate of mitochondrial genes were also extensively varied among BILs.

Conclusions

These novel findings unraveled an unusual mystery of the maternal inheritance and possible cause for heterogeneity of mitogenomes in rice population. The current piece of work will greatly develop our understanding of the plant nucleo-cytoplasmic interaction and their potential role in plant growth and developmental processes.
Transcriptome and metabolome reveal redirection of flavonoids in a white testa peanut mutant
Authors: Wan Liyun , Lei Yong , Yan Liying , Liu Yue , Pandey Manish K. , Wan Xia , Varshney Rajeev K. , Fang Jiahai , Liao Boshou
Published: April 2020

Background

Coat color determines both appearance and nutrient quality of peanut. White seed coat in peanut can enhance the processing efficiency and quality of peanut oil. An integrative analysis of transcriptomes, metabolomes and histocytology was performed on wsc mutant and its wild type to investigate the regulatory mechanisms underlying color pigmentation.

Result

Metabolomes revealed flavonoids were redirected in wsc, while multi-omics analyses of wsc mutant seeds and testae uncovered WSC influenced the flavonoids biosynthesis in testa as well as suberin formation, glycolysis, the TCA cycle and amino acid metabolism. The mutation also enhanced plant hormones synthesis and signaling. Further, co-expression analysis showed that FLS genes co-expressed with MBW complex member genes. Combining tissue expression patterns, genetic analyses, and the annotation of common DEGs for these three stages revealed that three testa specific expressed candidate genes, Araip.M7RY3, Aradu.R8PMF and Araip.MHR6K were likely responsible for the white testa phenotype. WSC might be regulated expression competition between FLS and DFR by controlling hormone synthesis and signaling as well as the MBW complex.

Conclusions

The results of this study therefore provide both candidate genes and novel approaches that can be applied to improve peanut with desirable seed coat color and flavonoid quality.
Crystal structure of DRIK1, a stress-responsive receptor-like pseudokinase, reveals the molecular basis for the absence of ATP binding
Authors: Aquino Bruno , da Silva Viviane C. H. , Massirer Katlin B. , Arruda Paulo
Published: April 2020

Background

Plants reprogram metabolism and development to rapidly adapt to biotic and abiotic stress. Protein kinases play a significant role in this process by phosphorylating protein substrates that activate or inactivate signaling cascades that regulate cellular and metabolic adaptations. Despite their importance in plant biology, a notably small fraction of the plant kinomes has been studied to date.

Results

In this report, we describe ZmDRIK1, a stress-responsive receptor-like pseudokinase whose expression is downregulated under water restriction. We show the structural features and molecular basis of the absence of ATP binding exhibited by ZmDRIK1. The ZmDRIK1 kinase domain lacks conserved amino acids that are essential for phosphorylation activity. The crystal structure of the ZmDRIK1 kinase domain revealed the presence of a spine formed by the side chain of the triad Leu240, Tyr363, and Leu375 that occludes the ATP binding pocket. Although ZmDRIK1 is unable to bind nucleotides, it does bind the small molecule ENMD-2076 which, in a cocrystal structure, revealed the potential to serve as a ZmDRIK1 inhibitor.

Conclusion

ZmDRIK1 is a novel receptor-like pseudokinase responsive to biotic and abiotic stress. The absence of ATP binding and consequently, the absence of phosphorylation activity, was proven by the crystal structure of the apo form of the protein kinase domain. The expression profiling of the gene encoding ZmDRIK1 suggests this kinase may play a role in downregulating the expression of stress responsive genes that are not necessary under normal conditions. Under biotic and abiotic stress, ZmDRIK1 is down-regulated to release the expression of these stress-responsive genes.
Feto-maternal outcomes of hypertensive disorders of pregnancy in Yekatit-12 Teaching Hospital, Addis Ababa: a retrospective study
Authors: Mengistu Mekoya D. , Kuma Tilahun
Published: April 2020

Background

In resource poor countries, hypertensive disorders of pregnancy are common and form one of the deadly triads, along with hemorrhage and infection, which contribute greatly to maternal and fetal jeopardy.

Methods

The aim of this study was to assess the prevalence of hypertensive disorders of pregnancy, and determine the effects of hypertensive disorders of pregnancy on the feto-maternal outcomes. It was a descriptive, cross-sectional, retrospective study on randomly selected 615 women who attended delivery at Yekatit-12 Teaching Hospital from 1st of July 2017 -1st of Jan 2018. Data was analyzed using SPSS version 20 software. Descriptive statistics were used to calculate rates. Chi-square statistics were used to estimate the associations among selected predictor variables. A p-value < 0.05 was taken as statistically significant.

Results

Out of the 615 study population, the prevalence of hypertensive disorders of pregnancy was found to be 25.4%, of which the majority (52.5%) was severe pre-eclampsia. Eclampsia accounted for 2.6%, and superimposed pre-eclampsia was 2.6%. The rate of severe pre-eclampsia with HELLP syndrome was 7.1% of all mothers with the hypertensive disorders. The majority of mothers with hypertensive disorders (59.6%) had age range of 25–34 years. About 46% of mothers required interventions to terminate the pregnancy either by cesarean section (42.3%) or instrumental deliveries (3.7%) due to conditions related to Hypertensive disorders. The rate of preterm, low birth weight, and low Apgar at 1st and 5thminutes accounted for 29.5, 24.4, 22.4 and 16.7% of neonates born to mothers with hypertensive disorders, respectively. Over 10.9% of neonates required resuscitation and 11.5% NICU referral. The rate of still birth was 3.8%.

Conclusion

The prevalence of hypertensive disorders of pregnancy is high in the study area and complicates maternal and fetal outcomes of the pregnancy. To deter its detrimental effects both on fetal and maternal outcomes of pregnancy, antenatal surveillance should be expanded to enable early detection, stringent follow-up and timely intervention in severely affected pregnancies.
Serum human epididymis protein 4 level as a predictor of clinical worsening in idiopathic pulmonary arterial hypertension: a pilot study
Authors: Jin Qi , Tang Yi , Liu Zhihong , Xie Wenlin , Luo Qin , Zhao Zhihui , Zhao Qing , Huang Zhiwei , Yu Xue , Yan Lu , Xiong Changming , Ni Xinhai , Yan Yinkun
Published: April 2020

Background

Human epididymis protein 4 (HE4) was proved to be a novel biomarker for left heart failure. The purpose of this exploratory study was to evaluate the role of HE4 in patients with idiopathic pulmonary arterial hypertension (IPAH) who usually have concurrent right heart failure.

Methods

55 patients with newly diagnosed IPAH were continuously enrolled and serum HE4 levels were assessed at baseline. All patients were followed up from the date of blood sampling, and a composite endpoint of clinical worsening was detailedly recorded.

Results

Serum levels of HE4 were significantly higher in IPAH patients than healthy controls (6.9 ± 2.2 vs 4.4 ± 0.9 ng/ml,p < 0.05) and increased as cardiac function deteriorated. HE4 levels correlated with endothelin-1 (r = 0.331,p < 0.01) and right atrial pressure (r = 0.30,p < 0.03). After a mean follow-up of 20 ± 10 months, 13 patients experienced clinical worsening. Receiver operating characteristic analysis showed that HE4 levels > 6.5 ng/ml discriminated clinical worsening with a sensitivity of 92.31% and a specificity of 59.52% (area under the curve [AUC] = 0.81). Multivariate Cox regression analysis demonstrated that HE4 (χ2: 5.10; hazard ratio [HR] = 1.26; 95% confidence interval: 1.03 to 1.55,p < 0.02) and pulmonary vascular resistance (χ2: 4.19; HR = 1.14; 95% confidence interval: 1.00–1.29,p < 0.04) were independently predictive of clinical worsening. Patients with HE4 > 6.5 ng/ml had a worse 2-year survival rate than those with HE4 ≤ 6.5 ng/ml (58.9% vs 96.2%,p < 0.001).

Conclusions

Serum levels of HE4 were elevated in IPAH patients and correlated with disease severity. HE4 was an independent predictor of clinical worsening in IPAH patients.
Genetic forms and pathophysiology of essential arterial hypertension in minor indigenous peoples of Russia
Authors: Mulerova Tatyana , Uchasova Evgenya , Ogarkov Michael , Barbarash Olga
Published: April 2020

Background

To study the genetic forms and pathophysiology of arterial hypertension by evaluating plasma renin activity in the Shors, minor indigenous peoples inhabiting the south of Western Siberia.

Methods

A single-stage study of indigenous (the Shors) and non-indigenous peoples living in the villages of Gornaya Shoria of the Kemerovo region in the south of Western Siberia was conducted in the period from 2013 to 2017. One thousand four hundred nine adults (901 Shors and 508 non-indigenous inhabitants) were recruited in the study using a continuous sampling plan. Arterial blood pressure was measured according to 2018 ESC/ESH guidelines for the management of arterial hypertension. All the respondents underwent clinical and instrumental examination. Plasma renin activity was determined by enzyme-linked immunoassay with the BRG kits (Germany). Polymorphisms of ACE (I/D, rs 4340), АGT (c.803 T > C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A > G, Ser49Gly, rs1801252) and ADRA2B (I/D, rs 28,365,031) genes were tested using polymerase chain reaction.

Results

Renin-dependent hypertensive patients prevailed in both ethnic groups (65.6% in the indigenous group vs. 89.8% in the non-indigenous group, p = 0.001). Prevalence of a volume-dependent AH was low in both groups (34.4% in the indigenous group vs. 10.2% in the non-indigenous group, р = 0.001). The D/D and Т/Т genotypes of the АСЕ [OR = 6.97; 95% CI (1.07–55.58)] and AGT [OR = 3.53; 95% CI (1.02–12.91)] genes were associated with the renin-dependent AH in the Shors. The C/C genotype of AGTR1 gene was found to predispose to the volume-dependent AH [OR = 5.25; 95% CI (1.03–27.89)]. The C/C genotype of AGTR1 gene was associated with moderate or high renin levels suggesting essential AH in the non-indigenous group [OR = 5.00; 95% CI (1.21–22.30), р = 0.029].

Conclusion

An in-depth understanding of AH pathophysiology and its genetic forms ensures the optimal choice of blood pressure-lowering treatment and optimizes AH control.
Epidemiological and molecular characterization of Streptococcus pneumoniae carriage strains in pre-school children in Arkhangelsk, northern European Russia, prior to the introduction of conjugate pneumococcal vaccines
Authors: Vorobieva S. Jensen V. , Furberg A-S , Slotved H-C , Bazhukova T. , Haldorsen B. , Caugant D. A. , Sundsfjord A. , Valentiner-Branth P. , Simonsen G. S.
Published: April 2020

Background

The 13-valent Pneumococcal Conjugate Vaccine (PCV-13) was introduced in the National Immunization Programme (NIP) schedule in Russia in March 2014. Previously, the 7-valent Pneumococcal Conjugate Vaccine (PCV-7) was marketed in Russia in 2009 but has never been offered for mass vaccination. A carriage study was performed among children in Arkhangelsk in 2006. The objective was to determine the prevalence of carriage, serotype distribution, antimicrobial susceptibility and the molecular structure of Streptococcus pneumoniae strains before marketing and introduction of PCV-13.

Methods

A cross-sectional study was conducted on a cluster-randomized sample of children and a self-administrated questionnaire for parents/guardians.  Nasopharyngeal samples were collected from 438 children younger than 7 years attending nurseries and kindergartens in the Arkhangelsk region, Russia. Detailed demographic data, as well as information about the child’s health, traveling, exposure to antimicrobials within the last 3 months and anthropometric measurements were collected for all study subjects. Variables extracted from the questionnaire were analysed using statistic regression models to estimate the risk of carriage. All pneumococcal  isolates were examined with susceptibility testing, serotyping and multilocus sequence typing.

Results

The overall prevalence of asymptomatic carriage was high and peaking at 36 months with a rate of 57%. PCV-13 covered 67.3% of the detected strains. High rates of non-susceptibility to penicillin, macrolides and multidrug resistance were associated with specific vaccine serotypes, pandemic clones, and local sequence types. Nine percent of isolates represented three globally disseminated disease-associated pandemic clones; penicillin- and macrolide-resistant clones NorwayNT-42 and Poland6B-20, as well as penicillin- and macrolide-susceptible clone Netherlands3-31. A high level of antimicrobial consumption was noted by the study. According to the parent’s reports, 89.5% of the children used at least one antimicrobial regime since birth. None of the hypothesised predictors of S. pneumoniae carriage were statistically significant in univariable and multivariable logistic models.

Conclusions

The study identified a high coverage of the PCV-13-vaccine, but serotype replacement and expansion of globally disseminated disease-associated clones with non-vaccine serotypes may be expected. Further surveillance of antimicrobial resistance and serotype distribution is therefore required.
Weakly-supervised convolutional neural networks of renal tumor segmentation in abdominal CTA images
Authors: Yang Guanyu , Wang Chuanxia , Yang Jian , Chen Yang , Tang Lijun , Shao Pengfei , Dillenseger Jean-Louis , Shu Huazhong , Luo Limin
Published: April 2020

Background

Renal cancer is one of the 10 most common cancers in human beings. The laparoscopic partial nephrectomy (LPN) is an effective way to treat renal cancer. Localization and delineation of the renal tumor from pre-operative CT Angiography (CTA) is an important step for LPN surgery planning. Recently, with the development of the technique of deep learning, deep neural networks can be trained to provide accurate pixel-wise renal tumor segmentation in CTA images. However, constructing the training dataset with a large amount of pixel-wise annotations is a time-consuming task for the radiologists. Therefore, weakly-supervised approaches attract more interest in research.

Methods

In this paper, we proposed a novel weakly-supervised convolutional neural network (CNN) for renal tumor segmentation. A three-stage framework was introduced to train the CNN with the weak annotations of renal tumors, i.e. the bounding boxes of renal tumors. The framework includes pseudo masks generation, group and weighted training phases. Clinical abdominal CT angiographic images of 200 patients were applied to perform the evaluation.

Results

Extensive experimental results show that the proposed method achieves a higher dice coefficient (DSC) of 0.826 than the other two existing weakly-supervised deep neural networks. Furthermore, the segmentation performance is close to the fully supervised deep CNN.

Conclusions

The proposed strategy improves not only the efficiency of network training but also the precision of the segmentation.
Improving the diagnosis of common parotid tumors via the combination of CT image biomarkers and clinical parameters
Authors: Zhang Dan , Li Xiaojiao , Lv Liang , Yu Jiayi , Yang Chao , Xiong Hua , Liao Ruikun , Zhou Bi , Huang Xianlong , Liu Xiaoshuang , Tang Zhuoyue
Published: April 2020

Background

Our study aims to develop and validate diagnostic models of the common parotid tumors based on whole-volume CT textural image biomarkers (IBMs) in combination with clinical parameters at a single institution.

Methods

The study cohort was composed of 51 pleomorphic adenoma (PA) patients and 42 Warthin tumor (WT) patients. Clinical parameters and conventional image features were scored retrospectively and textural IBMs were extracted from CT images of arterial phase. Independent-samples t test or Chi-square test was used for evaluating the significance of the difference among clinical parameters, conventional CT image features, and textural IBMs. The diagnostic performance of univariate model and multivariate model was evaluated via receiver operating characteristic (ROC) curve and area under ROC curve (AUC).

Results

Significant differences were found in clinical parameters (age, gender, disease duration, smoking), conventional image features (site, maximum diameter, time-density curve, peripheral vessels sign) and textural IBMs (mean, uniformity, energy, entropy) between PA group and WT group (P<0.05). ROC analysis showed that clinical parameter (age) and quantitative textural IBMs (mean, energy, entropy) were able to categorize the patients into PA group and WT group, with the AUC of 0.784, 0.902, 0.910, 0.805, respectively. When IBMs were added in clinical model, the multivariate models including age-mean and age-energy performed significantly better than the univariate models with the improved AUC of 0.940, 0.944, respectively (P<0.001).

Conclusions

Both clinical parameter and CT textural IBMs can be used for the preoperative, noninvasive diagnosis of parotid PA and WT. The diagnostic performance of textural IBM model was obviously better than that of clinical model and conventional image model in this study. While the multivariate model consisted of clinical parameter and textural IBM had the optimal diagnostic performance, which would contribute to the better selection of individualized surgery program.
Rituximab therapy for focal segmental glomerulosclerosis and minimal change disease in adults: a systematic review and meta-analysis
Authors: Hansrivijit Panupong , Cheungpasitporn Wisit , Thongprayoon Charat , Ghahramani Nasrollah
Published: April 2020

Background

Use of rituximab (RTX) for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is widely described in children. Clinical evidence in adults is limited. The objective of this study was to determine the treatment outcomes of RTX in adults with FSGS and MCD.

Methods

Ovid MEDLINE, SCOPUS, and Cochrane Database of Systematic Reviews were searched up to September 2019. Out of 699 studies, we included 16 studies describing the treatment outcomes of rituximab in adult patients with FSGS or MCD. Results were reported in remission rate and relapse rate. Serious adverse events were also reported.

Results

A total of 16 studies were included in our review and analysis. All studies were observational studies and included a total of 221 patients (23.1% FSGS, 76.9% MCD). Mean follow-up duration was 26.3 ± 12.8 months. From the analysis of five studies with FSGS patients (n = 51), the overall remission rate and relapse rate of RTX therapy was 53.6% (95% CI, 15.8–87.6%) and 47.3% (95% CI, 25.4–70.2%), respectively. Complete remission occurred in 42.9%. In contrast, from the analysis of 11 studies with MCD patients (n = 170), the overall remission rate and relapse rate of RTX therapy was 80.3% (95% CI, 68.5–88.5%) and 35.9% (95% CI, 25.1–48.4), respectively. Complete remission occurred in 74.7%. Subgroup analyses showed that overall remission and relapse were not different after adjusted for study year and RTX dose for both FSGS and MCD. Incidence of serious adverse events was 0.092 events/year.

Conclusions

Rituximab may be considered as an additional treatment to the standard therapy for adult patients with FSGS and MCD. Remissions and relapses are similar between FSGS and MCD. Serious adverse effects of rituximab were uncommon. We encourage further randomized controlled trials to confirm the efficacy of rituximab therapy in these patients.
Maternal health services utilization and maternal mortality in China: a longitudinal study from 2009 to 2016
Authors: Zhao Pengyu , Han Xueyan , You Lili , Zhao Yu , Yang Li , Liu Yuanli
Published: April 2020

Background

The Chinese government introduced the maternal health services as part of the Basic Public Health Service (BPHS) project in 2009. While China has made progress in reducing maternal mortality, the longitudinal association between the utilization rate of the maternal health services of the BPHS project and such reduction was rarely evaluated with robust methods.

Methods

We conducted a longitudinal study on the maternal health service utilization rates of the BPHS project and the maternal mortality ratios (MMR) in mainland China and its 31 provincial regions. The data were extracted from the National Health Statistic Yearbooks (2009–2016). Panel data models were used to evaluate the association between the utilization rate and the MMR after adjusting for available covariates on healthcare resources. Stepwise regression models were used to gauge the direction and magnitude of omitted variable bias.

Results

It was found that the service utilization rate increased from 79.24% in 2009 to 91.67% in 2016, while MMR decreased from 30.90 to 17.88 per 100,000 livebirths at the national level. The results of the fixed effects panel data model revealed that the utilization rate was associated with MMR deduction continuously. With every 1% increase in utilization rate, the maternal death would decrease by 0.35 per 100,000 livebirths after having the health resources variables adjusted.

Conclusions

The utilization of maternal health services increased continuously after the introduction of BPHS project in 2009 and MMR went downward from then on. The utilization of maternal health services did have significant association with MMR and could reduce MMR effectively. Such improvement could be attributed to the fact that this program was designed to serve the targeted population throughout the continuum of maternal care and the government’s rigorous efforts in stressing equality and standard care in program implementation.
Three-dimensional ultrasonographic features of diamniotic conjoined twins with body stalk anomaly
Authors: Xiang Guishuang , Wen Yanting , Zhang Li , Tong Xiaoqian , Li Lu
Published: April 2020

Background

Since conjoined twins were thought to be monoamniotic in the past, diamniotic conjoined twins would be improbable theoretically. Body stalk anomaly is a severe defect of the body wall, which is rare among twins. Body stalk anomaly in monochorionic diamniotic conjoined twins has never been reported prenatally so far as we know.

Case presentation

Here we present an extremely rare case of concordant body stalk anomaly in monochorionic diamniotic conjoined twins. Ultrasonography at 9 + 5 weeks revealed one chorionic and two amniotic cavities, close apposition of abdomen, limited movement, and common umbilical vessels. Follow-up ultrasonography at 11 + 6 weeks and 13 + 2 weeks showed close apposition of the lower abdominal region with cystic structures and a small bowel-like mass between the two fetuses. Three-dimensional ultrasonography assisted in observing the entire appearance of both twins in earlier first trimester, including amnioticity, conjoined region and umbilical vessels. We attribute this diamniotic conjoined twin in our case to the fusion theory. A single yolk sac was observed, challenging the idea that yolk sac number predicts amnionicity. Identification of single yolk sac and its allantois may form a common body stalk during this fusion, leading to concordant body stalk anomaly in monochorionic diamniotic twins.

Conclusions

Our case may provide important insights into both ultrasonographic features and embryogenesis of this extremely rare anomaly.
Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer
Authors: Kang Han Na , Kim Jae-Hwan , Park A-Young , Choi Jae Woo , Lim Sun Min , Kim Jinna , Shin Eun Joo , Hong Min Hee , Pyo Kyoung-Ho , Yun Mi Ran , Kim Dong Hwi , Lee Hanna , Yoon Sun Och , Kim Da Hee , Park Young Min , Byeon Hyung Kwon , Jung Inkyung , Paik Soonmyung , Koh Yoon Woo , Cho Byoung Chul , Kim Hye Ryun
Published: April 2020

Background

We investigated whether head and neck squamous cell carcinoma (HNSCC) patient-derived xenografts (PDXs) reaffirm patient responses to anti-cancer therapeutics.

Methods

Tumors from HNSCC patients were transplanted into immunodeficient mice and propagated via subsequent implantation. We evaluated established PDXs by histology, genomic profiling, and in vivo anti-cancer efficacy testing to confirm them as the authentic in vivo platform.

Results

From 62 HNSCCs, 15 (24%) PDXs were established. The primary cancer types were tongue (8), oropharynx (3), hypopharynx (1), ethmoid sinus cancer (1), supraglottic cancer (1), and parotid gland (1); six PDXs (40%) were established from biopsy specimens from advanced HNSCC. PDXs mostly retained donor characteristics and remained stable across passages. PIK3CA (H1047R), HRAS (G12D), and TP53 mutations (H193R, I195T, R248W, R273H, E298X) and EGFR, CCND1, MYC, and PIK3CA amplifications were identified. Using the acquisition method, biopsy showed a significantly higher engraftment rate when compared with that of surgical resection (100% [6/6] vs. 16.1% [9/56], P < 0.001). Specimens obtained from metastatic sites showed a significantly higher engraftment rate than did those from primary sites (100% [9/9] vs. 11.3% [6/53], P < 0.001). Three PDX models from HPV-positive tumors were established, as compared to 12 from HPV-negative (15.8% [3/19] and 27.9% [12/43] respectively, P = 0.311), suggesting that HPV positivity tends to show a low engraftment rate. Drug responses in PDX recapitulated the clinical responses of the matching patients with pan-HER inhibitors and pan-PI3K inhibitor.

Conclusions

Genetically and clinically annotated HNSCC PDXs could be useful preclinical tools for evaluating biomarkers, therapeutic targets, and new drug discovery.
Gastrointestinal peptides in children before and after hematopoietic stem cell transplantation
Authors: Skoczeń Szymon , Rej Magdalena , Kwiecińska Kinga , Pietrys Danuta , Tomasik Przemysław J. , Wójcik Małgorzata , Strojny Wojciech , Dłużniewska Agnieszka , Klimasz Katarzyna , Fijorek Kamil , Korostyński Michał , Piechota Marcin , Balwierz Walentyna
Published: April 2020

Background

Gastrointestinal tract function and it’s integrity are controlled by a number of peptides whose secretion is influenced by severe inflammation. In stomach the main regulatory peptide is ghrelin. For upper small intestine cholecystokinin and lower small intestine glucagon-like peptide- 1 are secreted, while fibroblast growth factor-21 is secreted by several organs, including the liver, pancreas, and adipose tissue [12]. Hematopoietic stem cell transplantation causes serious mucosal damage, which can reflect on this peptides.

Methods

The aim of the study was to determine fasting plasma concentrations of ghrelin, cholecystokinin, glucagon- like peptide-1, and fibroblast growth factor-21, and their gene expressions, before and 6 months after hematopoietic stem cell transplantation.27 children were studied, control group included 26 healthy children.

Results

Acute graft versus host disease was diagnosed in 11 patients (41%, n = 27). Median pre-transplantation concentrations of gastrointestinal peptides, as well as their gene expressions, were significantly lower in studied group compared with the control group. Only median of fibroblast growth factor-21 concentration was near-significantly higher before stem cell transplantation than in the control group. The post–hematopoietic transplant results revealed significantly higher concentrations of the studied peptides (except fibroblast growth factor-21) and respective gene expressions as compare to pre transplant results. Median glucagone like peptide-1 concentrations were significantly decreased in patients with features of acute graft versus host disease. Moreover, negative correlation between glucagone like peptide-1 concentrations and acute graft versus host disease severity was found.

Conclusions

Increased concentrations and gene expressions of gastrointestinal tract regulation peptides can be caused by stimulation of regeneration in the severe injured organ. Measurement of these parameters may be a useful method of assessment of severity of gastrointestinal tract complications of hematopoietic stem cell transplantation.
Characterization of LGR5 expression in poorly differentiated colorectal carcinoma with mismatch repair protein deficiency
Authors: Nakajima Tomoyuki , Uehara Takeshi , Iwaya Mai , Kobayashi Yukihiro , Maruyama Yasuhiro , Ota Hiroyoshi
Published: April 2020

Background

Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a promising intestinal stem cell and carcinoma stem cell marker. We examined the relationship between mismatch repair (MMR) protein deficiency and LGR5 expression in poorly differentiated (PD) colorectal carcinoma (CRC).

Methods

In 29 cases of PD-CRC, deficiencies in MMR proteins (MLH1, PMS2, MSH2, MSH6) and β-catenin expression were identified by immunohistochemistry (IHC). LGR5 expression was examined by the RNAscope assay in tissue microarrays.

Results

LGR5 H-scores in MMR-deficient (MMR-D) cases were significantly lower than those in MMR-proficient (MMR-P) cases (P = 0.0033). Nuclear β-catenin IHC scores in MMR-D cases were significantly lower than those in MMR-P cases (P = 0.0024). In all cases, there was a positive correlation between LGR5 H-score and nuclear β-catenin IHC score (r = 0.6796, P < 0.001). Even in MMR-D and MMR-P cases, there was a positive correlation between LGR5 H-score and nuclear β-catenin IHC score (r = 0.7180, P < 0.0085 and r = 0.6574, P < 0.003, respectively). MMR-D CRC cases showed low expression of LGR5, which may be due to low activation of the Wnt/β-catenin signaling pathway.

Conclusions

Our results reveal the relationship between LGR5 expression and MMR protein profiles in PD-CRC. A further study is warranted to confirm these findings.
Identification of CELSR2 as a novel prognostic biomarker for hepatocellular carcinoma
Authors: Xu Mingxing , Zhu Shu , Xu Ruiyun , Lin Nan
Published: April 2020

Background

CELSR2 is postulated to be a receptor involved in contact-mediated communication; however, the specific function of this particular member has not been determined in hepatocellular carcinoma (HCC).

Methods

Here, we explored the expression and function of CELSR2 in HCC patients through data mining and examined the results using clinical samples and in vitro experiments.

Results

It was found that CELSR2 mRNA and protein expression levels were significantly higher in cancerous tissue than in normal tissue. The increased mRNA expression of CELSR2 was significantly associated with overall survival (OS) in HCC patients. Moreover, the genetic alteration rate of CELSR2 gene in HCC can reach 8%, and these alterations would deeply influence its neighboring genes, then jointly affecting the occurrence and development of tumor through cell adhesion and numerous common carcinogenic pathways. Our in vitro results indicated that the depletion of CELSR2 inhibited liver cancer cell proliferation and invasion. Univariate and multivariate Cox regression analyses showed that CELSR2 could be viewed as an independent risk factor for HCC patients.

Conclusions

This study demonstrated that data mining could efficiently reveal the roles of CELSR2 in HCC and its potential regulatory networks. The CELSR2 protein level may serve as a novel prognostic biomarker for HCC.
Comparing efficacy of reduced-fluence and standard-fluence photodynamic therapy in the treatment of polypoidal choroidal vasculopathy
Authors: Ngo Wei Kiong , Chee Wai Kitt , Tan Colin S. , Lim Tock Han
Published: April 2020

Background

The EVEREST II study reported superior polyp closure rates and visual outcomes using combination standard photodynamic therapy (PDT) with intravitreal ranibizumab in the treatment of polypoidal choroidal vasculopathy (PCV). The optimal PDT protocol remains controversial and it is postulated that less intensive PDT strategies may reduce complications. We aimed to compare the efficacy of reduced and standard-fluence PDT.

Methods

Case-control review of 38 consecutive PDT-naïve macular PCV patients who underwent verteporfin PDT using one of two PDT regimens at a tertiary referral centre in an Asian population. Comparison of outcomes between standard-fluence PDT (light dose, 50 J/cm2; dose rate, 600 mW/cm2; wavelength, 689 nm PDT applied to the treatment eye for 83 s) and reduced-fluence PDT (light dose, 25 J/cm2; dose rate, 600 mW/cm2; wavelength, 689 nm PDT applied to the treatment eye for 42 s). Primary outcome measure was best corrected LogMAR visual acuity (VA). Secondary outcome measures included OCT measurements such as central retinal thickness (CRT), height of subfoveal sub-retinal fluid (SRF), central choroid thickness (CCT), mean number of PDT treatments needed, mean number of anti-VEGF injections needed, polyp closure and recurrence rates.

Results

Of these 38 eyes of 38 patients, an equal number of eyes (19 in each arm) were treated with standard-fluence and reduced-fluence PDT. Mean letter gain at 12 months for the standard-fluence group was 6.0 compared to 4.3 letters for the reduced-fluence group (p = 0.61). Similar results were observed at all time points. There was no statistically significant difference between the retinal and choroidal anatomical OCT outcomes, rates of polyp closure and recurrences between the two PDT regimens.

Conclusions

Reduced-fluence PDT was comparable to standard-fluence PDT in the treatment of PCV in terms of visual gains, clinical and anatomical OCT outcomes.
Effects of procedural justice on prospective antidepressant medication prescription: a longitudinal study on Swedish workers
Authors: Persson Viktor , Eib Constanze , Bernhard-Oettel Claudia , Leineweber Constanze
Published: April 2020

Background

Procedural justice has been linked to several mental health problems, but most studies have used self-reported data. There exist a need to assess the link between procedural justice and health using outcomes that are not only self-reported. The aim of the current study was to examine whether perceived procedural justice at work is prospectively associated with antidepressant medication prescription.

Methods

Data from 4374 participants from the Swedish Longitudinal Survey of Health (SLOSH) were linked to the Swedish National Prescribed Drug register. Based on their perceived procedural justice at two times (2010 and 2012), participants were divided into four groups: stable low, increasing, decreasing and stable high justice perceptions. Using Cox regression, we studied how the course of stability and change in perceived procedural justice affected the rate of prescription of antidepressant medication over the next 2 years. Participants with missing data and those who had been prescribed antidepressant medication in the period leading up to 2012 were excluded in the main analyses to determine incident morbidity.

Results

The results showed that after adjustment for sex, age, education, socioeconomic position, marital status, and insecure employment a decrease in perceived procedural justice over time was associated with greater receipt of antidepressants compared to people with stable high perceptions of procedural justice (HR 1.76, 95% CI: 1.16 to 2.68). Being female and having insecure employment were also associated with higher hazards of antidepressant prescription.

Conclusions

These findings strengthen the notion that procedural justice at work influences psychological well-being, as well as provide new insights into how procedural justice perceptions may affect mental health.
Knowledge and practice of health extension workers on drug provision for childhood illness in west Gojjam, Amhara, Northwest Ethiopia
Authors: Befekadu Ager , Yitayal Mezgebu
Published: April 2020

Background

The HEP was established decades ago to address preventive, promotive and selective curative services through Health Extension Workers (HEWs). However, knowledge and practice of HEWs on drug provision for childhood illnesses such as diarrhea, fever, and/or acute respiratory infection have not been well studied. This study aimed to assess the knowledge and practice of HEWs on drug provision for childhood illnesses.

Methods

An institutional-based cross-sectional study was conducted among 389 rural HEWs. The districts were selected by using simple random sampling technique, and all the HEWs in the districts were included in the study. Bivariable and multivariable logistic regressions were performed to see the association between knowledge and practice of HEWs on drug provision with the response variables.

Results

The study revealed that 57.5 and 66.8% of HEWs had good knowledge and practice on drug provision for childhood illnesses, respectively. Having college diploma (AOR = 5.59; 95% CI: 1.94, 16.11), 7–9 years (AOR = 2.7; 95% CI: 1.3, 5.5) and 10–12 years (AOR = 2.7; 95% CI: 1.4, 5.4) of experiences, being supervised quarterly (AOR = 0.24; 95% CI: 0.13, 0.47) and biannually (AOR = 0.11; 95% CI: 0.04, 0.30), and having national guideline (AOR = 0.22; 95% CI: 0.06, 0.90) were factors significantly associated with good knowledge. In addition, having college diploma (AOR =3.1; 95% CI: 1.1, 8.8), not receiving refreshment training (AOR = 0.31; 95% CI: 0.11, 0.91), being supervised biannually (AOR = 0.32, 95% CI: 0.13, 0.80), and not having national guideline (AOR = 0.16, 95% CI: 0.04, 0.60) were factors significantly associated with good practice.

Conclusion

The study indicated that a considerable number of HEWs had poor knowledge and practice on drug provision. Socio-demographic factors such as educational status, and work experience; and health systems and support related factors such as training, supervision, and availability of national guidelines, and training had a significant association with HEWs’ knowledge and practice on drug provision. Therefore, designing appropriate strategy and providing refreshment training, and improving supervision and availability of national guidelines for HEWs might improve the knowledge and practice of HEWs on drug provision.
Active play in ASP –a matched-pair cluster-randomized trial investigating the effectiveness of an intervention in after-school programs for supporting children’s physical activity
Authors: Riiser Kirsti , Richardsen Kåre Rønn , Haugen Anders L. H. , Lund Siv , Løndal Knut
Published: April 2020

Background

Interventions directed at after school programs (ASPs) have the potential to support physical activity (PA) in young children. Research has indicated that interventions that emphasize competence building among the ASP staff can lead to increased PA among the children. The present study evaluates the effectiveness of theActive Play in ASPintervention—a program for ASP staff aimed at supporting physical activity among first graders in ASP.

Methods

We used a matched-pair cluster randomized design and included 456 first graders from 14 schools in Norway. From these, 7 ASPs received the intervention (N = 229), while 7 acted as controls (N = 227). Measurements were taken at baseline, immediately post intervention (7 month follow-up) and after a year (19 month follow-up). The primary outcome was moderate to vigorous physical activity (MVPA), which was estimated with predefined cut points of counts per minute (CPM) and expressed as minutes/hour. Secondary outcomes were vigorous and light intensity physical activity (VPA and LPA) and sedentary behavior. The analyses of intervention effects were based on between-group differences in outcome changes between the 3 measurement points and were conducted using a mixed-effects model for repeated measures using categorical time. In exploratory analyses, we investigated gender, baseline body mass index, and baseline CPM as potential effect modifiers.

Results

No significant intervention effects was observed on MVPA (0.55 min/hour [99% CI -0.55:1.64]) or on the secondary outcomes, min/hour of LPA, VPA or sedentary behavior. Exploratory analyses indicated that among the 50% least physically active children at baseline, children in intervention ASPs reduced sedentary time from baseline to 19 months follow up by 1.67 min/hour (95% CI -3.12:-0.21) compared to the controls.

Conclusions

Although the intervention did not significantly increase the mean MVPA among the children in the intervention ASPs compared to controls, it did seem to have a small effect by reducing sedentary behavior time among the least active children. An even stronger emphasis on how to identify less active children and support their activity may be needed in order to increase their PA and further reduce sedentary behavior time.

Trial registration

ClinicalTrials;NCT02954614, Registered 3 November 2016, −Retrospectively registered, first participant enrolled August 2016
Forecasting the 2017/2018 seasonal influenza epidemic in England using multiple dynamic transmission models: a case study
Authors: Birrell Paul J. , Zhang Xu-Sheng , Corbella Alice , van Leeuwen Edwin , Panagiotopoulos Nikolaos , Hoschler Katja , Elliot Alex J. , McGee Maryia , Lusignan Simon de , Presanis Anne M. , Baguelin Marc , Zambon Maria , Charlett André , Pebody Richard G. , Angelis Daniela De
Published: April 2020

Background

Since the 2009 A/H1N1 pandemic, Public Health England have developed a suite of real-time statistical models utilising enhanced pandemic surveillance data to nowcast and forecast a future pandemic. Their ability to track seasonal influenza and predict heightened winter healthcare burden in the light of high activity in Australia in 2017 was untested.

Methods

Four transmission models were used in forecasting the 2017/2018 seasonal influenza epidemic in England: a stratified primary care model using daily, region-specific, counts and virological swab positivity of influenza-like illness consultations in general practice (GP); a strain-specific (SS) model using weekly, national GP ILI and virological data; an intensive care model (ICU) using reports of ICU influenza admissions; and a synthesis model that included all data sources. For the first 12 weeks of 2018, each model was applied to the latest data to provide estimates of epidemic parameters and short-term influenza forecasts. The added value of pre-season population susceptibility data was explored.

Results

The combined results provided valuable nowcasts of the state of the epidemic. Short-term predictions of burden on primary and secondary health services were initially highly variable before reaching consensus beyond the observed peaks in activity between weeks 3–4 of 2018. Estimates for R0 were consistent over time for three of the four models until week 12 of 2018, and there was consistency in the estimation of R0 across the SPC and SS models, and in the ICU attack rates estimated by the ICU and the synthesis model. Estimation and predictions varied according to the assumed levels of pre-season immunity.

Conclusions

This exercise successfully applied a range of pandemic models to seasonal influenza. Forecasting early in the season remains challenging but represents a crucially important activity to inform planning. Improved knowledge of pre-existing levels of immunity would be valuable.
The yield of immediate post lung biopsy CT in predicting iatrogenic pneumothorax
Authors: Brzezinski Rafael Y. , Vigiser Ifat , Fomin Irina , Israeli Lilach , Shenhar-Tsarfaty Shani , Bar-Shai Amir
Published: April 2020

Background

The most prevalent complication of percutaneous lung biopsy is pneumothorax (PNX). A routine immediate post-procedure CT scan (ICT) to spot PNX is done in many centers. However, the diagnostic yield of this practice has not been studied broadly. We sought to evaluate whether an ICT could replace the routine follow-up chest X-ray (CXR) in detecting procedure related PNX.

Methods

We examined case-records of 453 patients who underwent lung biopsy at our medical center. We analyzed findings from CXR performed 2-h after biopsy and from CT images at the site of biopsy acquired immediately after the procedure (ICT). Multivariate analysis was used to identify the risk factors for PNX, and we examined the concordance between ICT and CXR-2-h post-procedure.

Results

A total of 87 patients (19%) were diagnosed with PNX on CXR-2-h post-procedure. ICT detected 80.5% of diagnosed PNX (p <  0.01). However, ICT demonstrated a negative predictive value of only 94%, meaning 17 patients (6%) with a negative ICT did eventually develop PNX seen on CXR. Furthermore, bleeding surrounding the puncture area spotted on ICT negatively predicted the development of PNX (OR = 0.4 95% CI; 0.2–0.7).

Conclusions

We conclude that a CT scan performed immediately after percutaneous lung biopsy cannot replace the routine follow-up CXR in predicting iatrogenic PNX. Bleeding in the needle’s tract may lower the risk for procedure-related PNX.