bluuebunny/crossref_metadata_2025 huggingface dataset:
Intergenomic gene transfer in diploid and allopolyploid Gossypium
Authors: Zhao Nan , Grover Corrinne E. , Chen Zhiwen , Wendel Jonathan F. , Hua Jinping
Published: November 2019

Background

Intergenomic gene transfer (IGT) between nuclear and organellar genomes is a common phenomenon during plant evolution.Gossypiumis a useful model to evaluate the genomic consequences of IGT for both diploid and polyploid species. Here, we explore IGT among nuclear, mitochondrial, and plastid genomes of four cotton species, including two allopolyploids and their model diploid progenitors (genome donors,G. arboreum: A2andG. raimondii: D5).

Results

Extensive IGT events exist for both diploid and allotetraploid cotton (Gossypium) species, with the nuclear genome being the predominant recipient of transferred DNA followed by the mitochondrial genome. The nuclear genome has integrated 100 times more foreign sequences than the mitochondrial genome has in total length. In the nucleus, the integrated length of chloroplast DNA (cpDNA) was between 1.87 times (in diploids) to nearly four times (in allopolyploids) greater than that of mitochondrial DNA (mtDNA). In the mitochondrion, the length of nuclear DNA (nuDNA) was typically three times than that of cpDNA.Gossypiummitochondrial genomes integrated three nuclear retrotransposons and eight chloroplast tRNA genes, and incorporated chloroplast DNA prior to divergence between the diploids and allopolyploid formation. For mitochondrial chloroplast-tRNA genes, there were 2-6 bp conserved microhomologies flanking their insertion sites across distantly related genera, which increased to 10 bp microhomologies for the four cotton species studied. For organellar DNA sequences, there are source hotspots, e.g., theatp6-trnWintergenic region in the mitochondrion and the inverted repeat region in the chloroplast. Organellar DNAs in the nucleus were rarely expressed, and at low levels. Surprisingly, there was asymmetry in the survivorship of ancestral insertions following allopolyploidy, with mostnumts(nuclear mitochondrial insertions) decaying or being lost whereas mostnupts(nuclear plastidial insertions) were retained.

Conclusions

This study characterized and compared intracellular transfer among nuclear and organellar genomes within two cultivated allopolyploids and their ancestral diploid cotton species. A striking asymmetry in the fate of IGTs in allopolyploid cotton was discovered, withnumtsbeing preferentially lost relative tonupts.Our results connect intergenomic gene transfer with allotetraploidy and provide new insight into intracellular genome evolution.
Human gastric magnet-controlled capsule endoscopy conducted in a standing position: the phase 1 study
Authors: Cheng Chun-sheng , Sun Ting-ji , Zhang Hou-de
Published: November 2019

Background

Current magnet-controlled capsule endoscopy (MCE) for the stomach is not yet satisfactory with respect to navigation control, especially in the gastric fundus and cardia. A newly developed MCE system conducted in a standing rather than supine position may improve capsule maneuverability within the stomach. The aim of this phase 1 study was to assess the feasibility and safety of this system for examining the human stomach in healthy volunteers.

Methods

A cohort of 31 healthy volunteers were enrolled. Each swallowed a capsule after drinking water and gas producing agents intended to produce distention. Under the newly developed standing MCE system, subjects were examined endoscopically while standing with external guide magnets placed on the abdominal wall and left lower chest. Safety, gastric preparation, maneuverability, visualization of anatomical landmarks and the gastric mucosa, and examination time were the primary parameters assessed. The gastric preparation and examination procedures were well accepted by the subjects and there were no adverse events.

Results

Gastric examination took 27.8 ± 8.3 min (12–45 min). Gastric cleanliness was good in 24 participants (77.4%) and moderate in 7 participants (22.6%). Gastric distention was good in all of 31 participants (100%). Capsule maneuverability was also graded as good in all 31 subjects (100%), and manipulation in the fundus and cardia regions was as easy as that in the antrum and body. Visualization of the gastric cardia, fundus, body, angulus, antrum and pylorus was assessed subjectively as complete in all 31 subjects (100%). Visualization of the gastric mucosa was also good (> 75%) in all 31 subjects (100%). In areas where the mucosa could not be visualized, the low visibility was due to opaque fluid or foam. Polyps and erosive lesions were found in 25 subjects.

Conclusion

MCE of the stomach conducted in a standing position is feasible and safe with satisfactory maneuverability.
Clinical manifestations and multi-slice computed tomography characteristics of solid pseudopapillary neoplasms of the pancreas between males and females
Authors: Shi Shuguang , Zhou Ying , Hu Chunhong
Published: November 2019

Background

Solid-pseudo papillary neoplasms of pancreas (SPNP) are rare in men and are often misdiagnosed. This study aimed to analyze the clinical and multi-slice computer tomography (MSCT) features of patients with SPNP, and examine the differences between males and females.

Methods

In this retrospective cohort study, the clinical and imaging data of 29 patients with histolopathologically confirmed SPNP (seven males and 22 females) that underwent radical resection, and underwent preoperative MSCT at the First People’s Hospital of Lianyungang between August 2010 and December 2018 were collected. All MSCT images were reviewed by two radiologists; disagreements were ruled by a third one.

Results

The median age of the 29 patients with SPNP was 30 (range, 12–70) years. The male patients were older than the female patients [median, 56 (28–66) vs. 29 (12–70), P = 0.012]. The median tumor size was 3.9 (range, 2.0–6.4) cm in the male SPNP patients, which was significantly lower than the 7.0 (range, 4.6–14.6) cm in the female patients (P < 0.001). The calcification rate of the SPNP was significantly higher in male than in female patients (P = 0.013). The percentage of solid tumor was higher in males than in females (P = 0.036). Capsule, bleeding, and enhancement in the arterial and venous phases were not significantly different between the male and female patients (all P > 0.05).

Conclusion

The imaging features of male SPNP are distinct from those of female patients. In males with pancreatic lesions, MSCT generally shows relatively small lesions with higher percentages of solid components and calcification, with typical enhancement suggesting SPNP.
Primary low grade myxofibrosarcoma of the liver with benign presentation but malignant outcome: a case report
Authors: Shao Zigong , Jiao Baoping , Yu Juanhan , Liu Hao
Published: November 2019

Background

Myxofibrosarcoma (MFS) is most often found on the limbs of aged male people, but extremely uncommon in the liver.

Case presentation

A 52-year-old female patient with a liver mass was diagnosed as a primary MFS. It had no obvious abdominal symptoms, and the tumor was resected with an extended margin. Three years after the surgery, the patient was readmitted for peritoneal metastasis and passed away 4 months later. The tumor has a benign presentation, but malignant outcome.

Conclusions

Comprehensive radiological inspection, intensive preoperative evaluation, careful design of operating procedures, wide margin resection, consecutive treatment, and strict periodical follow-ups should be taken to ensure a better prognosis of this kind of neoplastic disease.
Determination of the androgen receptor status of circulating tumour cells in metastatic breast cancer patients
Authors: Krawczyk Natalia , Neubacher Melissa , Meier-Stiegen Franziska , Neubauer Hans , Niederacher Dieter , Ruckhäberle Eugen , Mohrmann Svjetlana , Hoffmann Jürgen , Kaleta Thomas , Banys-Paluchowski Malgorzata , Reinecke Petra , Esposito Irene , Janni Wolfgang , Fehm Tanja
Published: November 2019

Background

The prognostic relevance of circulating tumour cells (CTCs) in metastatic breast cancer (MBC) patients has been confirmed by several clinical trials. However, predictive blood-based biomarkers for stratification of patients for targeted therapy are still lacking. The DETECT studies explore the utility of CTC phenotype for treatment decisions in patients with HER2 negative MBC. Associated with this concept is a plethora of translational projects aiming to identify potential predictive biomarkers. The androgen receptor (AR) is expressed in over 70% of hormone receptor-positive and up-to 45% of triple-negative tumours. Studies has indicated the promising nature of AR as a new therapy target with a clinical benefit rate for anti-AR treatment in MBC patients up to 25% The aim of this analysis was the characterization of CTCs regarding the expression of the AR using immunofluorescence.

Methods

MBC patients were screened for the HER2-status of CTCs in the DETECT studies. In a subset of CTC-positive patients (n = 67) an additional blood sample was used for immunomagnetic enrichment of CTCs using the CellSearch® Profile Kit prior to transfer of the cells onto cytospin slides. Establishment of immunofluorescence staining for the AR was performed using prostate cancer cell lines LNCaP and DU145 as positive and negative control, respectively. Staining of DAPI, pan-cytokeratin (CK) and CD45 was applied to identify nucleated epithelial cells as CTCs and to exclude leucocytes.

Results

Co-staining of the AR, CK and CD45 according to the above mentioned workflow has been successfully established using cell lines with known AR expression spiked into the blood samples from healthy donors. For this translational project, samples were analysed from 67 patients participating in the DETECT studies. At least one CTC was detected in 37 out of 67 patients (56%). In 16 of these 37 patients (43%) AR-positive CTCs were detected. In eight out of 25 patients (32%) with more than one CTC, AR-positive and AR-negative CTCs were observed.

Conclusion

In 43% of the analysed CTC samples from patients with MBC the AR expression has been detected. The predictive value of AR expression in CTCs remains to be evaluated in further trials.
Epibulbar complex choristoma with simultaneous involvement of eyelid: a case report
Authors: Hsia Yun , Lien Huang-Chun , Wang I-Jong , Liao Shu-Lang , Wei Yi-Hsuan
Published: November 2019

Background

Epibulbar complex choristoma, a rare congenital epibulbar tumor, has many diverse forms. Reviewing the literature, it can present clinically as either a circumferential or isolated epibulbar mass, limbal tumor, lateral canthal mass, aggregate of ectopic cilia in the upper eyelid, eyelid mass mimicking chalazion, or lacrimal caruncle mass. The management depends on the extent of involvement, the risk of amblyopia, and cosmetic concerns. Here, we report an atypical presentation of epibulbar complex choristoma with simultaneous eyelid involvement.

Case presentation

A 1-month-old full-term boy was brought to our clinic with congenital epibulbar mass of the right eye with simultaneous eyelid involvement. Dilated fundus examination was unremarkable. Survey for linear nevus sebaceous Jadassohn was negative. Due to concerns of possible amblyopia and cosmetics, lamellar keratectomy, sclerotomy, and conjunctivoplasty were performed to remove the epibulbar lesion. The eyelid defect was reconstructed with 6–0 Vicryl sutures. Histopathological examination reported complex choristoma. Upon three-year follow-up, low astigmatism and favorable cosmetics results were achieved.

Conclusions

Congenital complex choristoma can present clinically as an epibulbar mass with eyelid involvement. The management depends on the extent of involvement, the risk of amblyopia, and cosmetic concerns. The method of eyelid reconstruction should be tailored according to the residual eyelid defect.
Schoolteachers’ experiences of implementing school-based vaccination programs against human papillomavirus in a Chinese community: a qualitative study
Authors: Siu Judy Yuen-man , Lee Albert , Chan Paul K. S.
Published: November 2019

Background

Cervical cancer was the fourth most common cancer among women worldwide in 2012 and was the eighth most common cancer in 2014 and the eighth greatest cause of female cancer deaths in Hong Kong in 2015. Human papillomavirus (HPV) vaccination has been clinically documented to have a high efficacy in reducing HPV-related cervical intraepithelial neoplasia incidence. Therefore, receiving vaccination is a crucial public health measure to reduce disease burden. Significant others, such as schools and schoolteachers, have prominent influence in shaping adolescents’ health perceptions and behavior. Therefore, the perspective of schools and schoolteachers regarding vaccination can significantly influence students’ acceptance and accessibility of the vaccine. However, few studies have analyzed the perceptions of schoolteachers toward HPV vaccination, and even fewer have concerned how schoolteachers’ perceptions influence their schools’ motivation in implementing school-based HPV vaccination programs. This study was thus conducted to fill this literature gap.

Methods

With a Chinese community as the field site of this study, a qualitative approach of five focus group interviews was conducted with 35 schoolteachers from five primary and eight secondary schools in Hong Kong between July 2014 and January 2015. Thematic content analysis was used for data analysis.

Results

Perceptual, institutional, student and parental, and collaborator barriers interacted to discourage the sampled schoolteachers from organizing school-based HPV vaccination programs. Lack of knowledge regarding HPV vaccination, perception of HPV vaccination as inappropriate given the students’ age, violation of traditional cultural values, lack of perceived needs and perceived risk, opposition from schools, low priority of HPV vaccination over other health education topics, lack of government support, lack of interest from parents and students, and lack of confidence in implementing organizations, all were the mentioned barriers.

Conclusions

The sampled schoolteachers were demotivated to organize school-based HPV vaccination programs because of their perceptions and various social and cultural factors. As significant influencers of adolescent students, schoolteachers and schools should receive more support and information on organizing school-based HPV vaccination programs in the future.
Altered expression of DLG1-AS1 distinguished papillary thyroid carcinoma from benign thyroid nodules
Authors: He Tao , Wang Huan , Sun Jiangming , Wu Jie , Gong Fakuo , Li Shujun , Wang Hui , Li Yufeng
Published: November 2019

Background

Benign thyroid nodules (BTN) are frequently diagnosed as papillary thyroid carcinoma (PTC), leading to unnecessary treatment. We found that plasma lncRNA DLG1-AS1 was upregulated in PTC patients but not in BTN patients and healthy controls.

Methods

In this study DLG1-AS1 and miR-199a-3p in plasma of both PTC patients and BTN patients were detected by qPCR. ROC curve analysis was performed for diagnostic analysis. Overexpression experiments were performed to analyze the interaction between DLG1-AS1 and miR-199a-3p. CCK-8 assay was performed to analyze cell proliferation.

Results

In this study, upregulation of DLG1-AS1 distinguished PTC patients from BTN patients and healthy controls. Plasma miR-199a-3p was downregulated in PTC patients compared with healthy controls and BTN patients. Plasma levels of miR-199a-3p were inversely correlated in PTC patients, but not in BTN patients and healthy controls. miR-199a-3p overexpression failed to significantly affect DLG1-AS1, while DLG1-AS1 overexpression resulted in downregulated miR-199a-3p, In addition, DLG1-AS1 overexpression promoted the proliferation of PTC cells. miR-199a-3p overexpression played an opposite role and attenuated the effects of DLG1-AS1 overexpression.

Conclusions

Therefore, DLG1-AS1 may promote PTC by downregulating miR-199a-3p.
Clinical significance of the preoperative main pancreatic duct dilation and neutrophil-to-lymphocyte ratio in pancreatic neuroendocrine tumors (PNETs) of the head after curative resection
Authors: Zhou Bo , Zhan Canyang , Xiang Jie , Ding Yuan , Yan Sheng
Published: November 2019

Background

The present study aimed to investigate the prognostic significance of preoperative main pancreatic duct dilation and the neutrophil-to-lymphocyte ratio (PD-NLR) in pancreatic neuroendocrine tumors (PNETs) of the head after curative resection.

Methods

Sixty-four consecutive PNETs of the head that underwent curative resection were included in the study. Preoperative main pancreatic duct dilation (PD) was defined as a pancreatic duct dilation greater than 3 mm before surgery. Patients with both PD and an elevated NLR (> 3.13), with PD or elevated NLR, or neither of these characteristics were allocated a PD-NLR score of 2, 1, or 0, respectively. Univariate, multivariate and Kaplan-Meier analyses were used to calculate overall survival (OS) and disease-free survival (DFS).

Results

Preoperative PD-NLR score was correlated with tumor size (P = 0.005), T-stage (P = 0.016), lymph node metastasis (P <  0.001), distant metastasis (P = 0.005), type of hormone production (P = 0.006), perineural invasion (P = 0.014), and WHO classification (P <  0.001). Patients with a high PD-NLR score had a significantly poor OS and DFS relative to those with a low PD-NLR score (P <  0.001). In the multivariate analysis, PD-NLR score was an independent predictor of OS and DFS for PNET of the head (both P <  0.05). In the analyses of the various subgroups, preoperative PD-NLR score was also a predictor of OS and DFS. Additionally, the survival predictive capability of PD-NLR score was superior to that of WHO classification.

Conclusions

Despite the retrospective nature and small sample size of the present study, the results suggest that preoperative PD-NLR score can serve as an independent prognostic marker of early survival in patients with PNETs of the head undergoing curative resection. Further large prospective studies are necessary to validate our findings.
Antimicrobial and antibiofilm activities of Casearia sylvestris extracts from distinct Brazilian biomes against Streptococcus mutans and Candida albicans
Authors: Ribeiro Sabrina M. , Fratucelli Érick D. O. , Bueno Paula C. P. , de Castro Marlene Kelly V. , Francisco Amanda Alcalá , Cavalheiro Alberto José , Klein Marlise I.
Published: November 2019

Background

Dental caries is a biofilm-diet-dependent worldwide public health problem, and approaches against microorganisms in cariogenic biofilms are necessary.

Methods

The antimicrobial and antibiofilm activities of 12 Casearia sylvestris extracts (0.50 mg/mL) from different Brazilian biomes (Atlantic Forest, Cerrado, Caatinga, Pampa, and Pantanal) and varieties (sylvestris, lingua, and intermediate) were tested against two species found in cariogenic biofilms (Streptococcus mutans and Candida albicans). The extracts effective against S. mutans were used to evaluate the "adhesion strength" of this bacterium to the salivary pellicle and initial glucan matrix and the S. mutans-GtfB activity. Also, the antimicrobial activity against S. mutans of three fractions (methanol, ethyl acetate, and hexane; 0.25 mg/mL) from the extracts was evaluated.

Results

Three extracts from the Atlantic Forest variety sylvestris (FLO/SC, GUA/CE, PRE/SP) reduced ≥50% (> 3 logs) S. mutans viable population (p < 0.0001 vs. vehicle), while two extracts from the same biome and variety (PAC/CE, PRE/SP) decreased ≥50% of the viable counts of C. albicans (p < 0.0001 vs. vehicle). For S. mutans biofilms, three extracts (GUA/CE, PAC/CE, PRE/SP) reduced the biomass by ≥91% (p > 0.0001 vs. vehicle) and 100% of the microbial population (p < 0.0001 vs. vehicle). However, for the fungal biofilm, two extracts (PAC/CE, PRE/SP) reduced the viable counts by ≥52% (p < 0.0001 vs. vehicle), but none reduced biomass. The extracts with higher antimicrobial and antibiofilm activities presented higher content of clerodane-type diterpenes and lower content of glycosylated flavonoids than the less active extracts. The extracts had no effect on the removal of cells adhered to the pellicle (p > 0.05 vs. vehicle) while promoted the detachment of a larger number of S. mutans cells from GtfB-glucan matrix (p < 0.0031 vs. vehicle), and FLO/SC, GUA/CE and PRE/SP reduced the quantity of glucans (p < 0.0136 vs. vehicle). Only the ethyl acetate fractions reduced the microbial population of S. mutans (p < 0.0001 vs. vehicle), except for one (PAC/CE). Among the ethyl acetate fractions, three from var. lingua (two from Cerrado, and one from Cerrado/Caatinga) reduced ≥83% of the microbial population.

Conclusions

C. sylvestris extracts from Atlantic Forest var. sylvestris and ethyl acetate fractions from Cerrado and Cerrado/Caatinga var. lingua may be used as a strategy against cariogenic microorganisms.
Knowledge, attitude, and use of mHealth technology among students in Ghana: A university-based survey
Authors: Peprah Prince , Abalo Emmanuel Mawuli , Agyemang-Duah Williams , Gyasi Razak M , Reforce Okwei , Nyonyo Julius , Amankwaa Godfred , Amoako Jones , Kaaratoore Paulinus
Published: November 2019

Background

Interest in mHealth interventions, defined as the use of mobile phones to access healthcare is increasingly becoming popular globally. Given its technology-based applications, university students may be key clients of the mHealth adoption but studies are rare in sub-Saharan Africa. This study provides a snapshot and baseline evidence on knowledge, attitude and use of mHealth among university students in Ghana.

Methods

Using a self-administered questionnaire, we collected data between April and June 2017 from 963 randomly sampled undergraduate students at the Kwame Nkrumah University of Science and Technology (KNUST). Pearson’s Chi-square (χ2) test assessed the differences between variables whilst  logistic regression models estimated the independent predictors of use of mHealth with p < 0.05 as significant.

Results

Knowledge on mHealth was moderately high. Specifically, more than half of the sample reported awareness of mHealth although the prevalence of use of mHealth stood at 51%. Logistic regressions revealed that mHealth use was positively associated with respondents’ year (second year: OR = 1.704, 95% CI: 1.185–2.452, and third year: OR = 1.528, 95% CI: 1.060–2.202), and monthly income (OR:3.112, 95%CI: 1.180-8.211). However, ethnicity [(OR = 0.761, 95% CI (0.580–0.997)] was negatively associated with the use of mHealth technology.

Conclusion

Findings suggest that knowledge of mHealth among university students is low. Policy and public health interventions for urgent awareness creation and promotion of use of mHealth as well as its possible integration into the mainstream healthcare system in Ghana are timely.
Application of machine learning methodology to assess the performance of DIABETIMSS program for patients with type 2 diabetes in family medicine clinics in Mexico
Authors: You Yue , Doubova Svetlana V. , Pinto-Masis Diana , Pérez-Cuevas Ricardo , Borja-Aburto Víctor Hugo , Hubbard Alan
Published: November 2019

Background

The study aimed to assess the performance of a multidisciplinary-team diabetes care program called DIABETIMSS on glycemic control of type 2 diabetes (T2D) patients, by using available observational patient data and machine-learning-based targeted learning methods.

Methods

We analyzed electronic health records and laboratory databases from the year 2012 to 2016 of T2D patients from six family medicine clinics (FMCs) delivering the DIABETIMSS program, and five FMCs providing routine care. All FMCs belong to the Mexican Institute of Social Security and are in Mexico City and the State of Mexico. The primary outcome was glycemic control. The study covariates included: patient sex, age, anthropometric data, history of glycemic control, diabetic complications and comorbidity. We measured the effects of DIABETIMSS program through 1) simple unadjusted mean differences; 2) adjusted via standard logistic regression and 3) adjusted via targeted machine learning. We treated the data as a serial cross-sectional study, conducted a standard principal components analysis to explore the distribution of covariates among clinics, and performed regression tree on data transformed to use the prediction model to identify patient sub-groups in whom the program was most successful. To explore the robustness of the machine learning approaches, we conducted a set of simulations and the sensitivity analysis with process-of-care indicators as possible confounders.

Results

The study included 78,894 T2D patients, from which 37,767patients received care through DIABETIMSS. The impact of DIABETIMSS ranged, among clinics, from 2 to 8% improvement in glycemic control, with an overall (pooled) estimate of 5% improvement. T2D patients with fewer complications have more significant benefit from DIABETIMSS than those with more complications. At the FMC’s delivering the conventional model the predicted impacts were like what was observed empirically in the DIABETIMSS clinics. The sensitivity analysis did not change the overall estimate average across clinics.

Conclusions

DIABETIMSS program had a small, but significant increase in glycemic control. The use of machine learning methods yields both population-level effects and pinpoints the sub-groups of patients the program benefits the most. These methods exploit the potential of routine observational patient data within complex healthcare systems to inform decision-makers.
Medroxyprogesterone acetate causes the alterations of endoplasmic reticulum related mRNAs and lncRNAs in endometrial cancer cells
Authors: Cao Wenjiao , Gao Wuyuan , Zheng Panchan , Sun Xiao , Wang Lihua
Published: November 2019

Background

Progestin is effective to promote endometrial cancer (EC) cells apoptosis, however, continuous progestin administration causes low level of progestin receptor B (PRB), further resulting in progestin resistance. Here, we performed microarray analysis on Ishikawa cells (PRB+) treated with medroxyprogesterone acetate (MPA) to explore the molecular mechanism underlying the inhibitory influence of MPA on PRB+ EC cells.

Methods

Microarray analysis was performed by using Ishikawa cells (PRB+) treated with MPA. Differentially expressed mRNA and long noncoding RNAs (lncRNAs) were identified. Furthermore, the functions of these mRNAs and lncRNAs were predicted by functional enrichment analysis. QRT-PCR was further performed to verify the microarray data.

Results

A total of 358 differentially expressed genes and 292 lncRNAs were identified in Ishikawa cells (PRB+) treated with MPA. QRT-PCR verified these data. Functional enrichment analysis identified endoplasmic reticulum (ER) stress as the key pathway involved in the inhibitory effect of MPA on EC cells. And the ER stress apoptotic molecule CHOP and ER stress related molecule HERPUD1 were both highly expressed in Ishikawa cells (PRB+) treated with MPA. Co-expression analysis showed lnc-CETP-3 was highly correlated with CHOP and HERPUD1, suggesting it might participate in ER stress pathway-related EC cell apoptosis caused by MPA. In addition, compared with untreated cells, lnc-CETP-3, CHOP and HERPUD1 were significantly up-regulated in Ishikawa cells (PRB+) treated with MPA, whereas they have no statistical significance in KLE cells (PRB-).

Conclusions

MPA may activate ER stress by progesterone-PRB pathway to up-regulate CHOP expression, which may be one of the molecular mechanisms underlying the inhibitory effect of MPA on EC cells with PRB+. Lnc-CETP-3 might be involved in this process. These findings may provide therapeutic targets for EC patients with PRB-, and resistance-related targets to increase the sensitivity of MPA on EC cells.
Systemic inflammatory response to inhaled endotoxin does not correlate with airway response
Authors: Sood Amika K. , Burbank Allison J. , Lawson Michael , Zhou Haibo , Wells Heather B. , Peden David B. , Hernandez Michelle L.
Published: November 2019

Background

Endotoxin is a component of particulate matter linked to respiratory disease. Our group has shown that experimental endotoxin inhalation challenge reproducibly triggers neutrophilic inflammation in the airways and in peripheral blood. Sputum induction is currently the only available method for assessing airway neutrophilia but is laborious and time-consuming. This analysis examined the correlation between systemic and airway inflammatory responses to endotoxin to determine if peripheral blood could serve as a surrogate marker for neutrophilic airway inflammation.

Methods

We conducted a retrospective study of 124 inhaled endotoxin challenges conducted at our center using 20,000 endotoxin units (EU) of Clinical Center Reference Endotoxin (CCRE). Venipuncture and induced sputum samples were obtained at baseline and 6 hours after completion of endotoxin challenge. The relationship between change in sputum neutrophils (post-challenge – baseline) and change in peripheral blood neutrophils (post-challenge – baseline) was assessed using Spearman’s correlation analyses.

Results

Inhaled endotoxin induced a significant increase in mean sputum percent neutrophils and peripheral blood absolute neutrophil counts in healthy adults with or without mild asthma, but no significant correlation was found between airway and systemic neutrophilia (r = 0.13, p = 0.18). Stratification by degree of airway neutrophil response and by atopic or asthmatic status did not change the results.

Conclusions

Inhalation challenge with endotoxin safely and effectively induces airway neutrophilic inflammation in most individuals. Increases in endotoxin-induced peripheral blood neutrophils do not correlate well with airway responses and should not be used as a surrogate marker of airway inflammation.
Diagnostic test interpretation and referral delay in patients with interstitial lung disease
Authors: Pritchard David , Adegunsoye Ayodeji , Lafond Elyse , Pugashetti Janelle Vu , DiGeronimo Ryan , Boctor Noelle , Sarma Nandini , Pan Isabella , Strek Mary , Kadoch Michael , Chung Jonathan H. , Oldham Justin M.
Published: November 2019

Background

Diagnostic delays are common in patients with interstitial lung disease (ILD). A substantial percentage of patients experience a diagnostic delay in the primary care setting, but the factors underpinning this observation remain unclear. In this multi-center investigation, we assessed ILD reporting on diagnostic test interpretation and its association with subsequent pulmonology referral by a primary care physician (PCP).

Methods

A retrospective cohort analysis of patients referred to the ILD programs at UC-Davis and University of Chicago by a PCP within each institution was performed. Computed tomography (CT) of the chest and abdomen and pulmonary function test (PFT) were reviewed to identify the date ILD features were first present and determine the time from diagnostic test to pulmonology referral. The association between ILD reporting on diagnostic test interpretation and pulmonology referral was assessed, as was the association between years of diagnostic delay and changes in fibrotic features on longitudinal chest CT.

Results

One hundred and forty-six patients were included in the final analysis. Prior to pulmonology referral, 66% (n = 97) of patients underwent chest CT, 15% (n = 21) underwent PFT and 15% (n = 21) underwent abdominal CT. ILD features were reported on 84, 62 and 33% of chest CT, PFT and abdominal CT interpretations, respectively. ILD reporting was associated with shorter time to pulmonology referral when undergoing chest CT (1.3 vs 15.1 months, respectively; p = 0.02), but not PFT or abdominal CT. ILD reporting was associated with increased likelihood of pulmonology referral within 6 months of diagnostic test when undergoing chest CT (rate ratio 2.17, 95% CI 1.03–4.56; p = 0.04), but not PFT or abdominal CT. Each year of diagnostic delay was associated with a 1.8% increase in percent fibrosis on chest CT. Patients with documented dyspnea had shorter time to chest CT acquisition and pulmonology referral than patients with documented cough and lung crackles.

Conclusions

Determinants of ILD diagnostic delays in the primary care setting include underreporting of ILD features on diagnostic testing and prolonged time to pulmonology referral even when ILD is reported. Interventions to modulate these factors may reduce ILD diagnostic delays in the primary care setting.
The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS
Authors:   for the SPIROMICS Investigators,, Wells J. Michael , Xing Dongqi , Viera Liliana , Burkes Robert M. , Wu Yixin , Bhatt Surya P. , Dransfield Mark T. , Couper David J. , O’Neal Wanda , Hoffman Eric A. , Gaggar Amit , Barjaktarevic Igor , Curtis Jeffrey L. , Labaki Wassim W. , Han Mei Lan K. , Freeman Christine M. , Putcha Nirupama , Schlange Thomas , Blalock J. Edwin
Published: November 2019

Background

Pulmonary and systemic inflammation are central features of chronic obstructive pulmonary disease (COPD). Previous studies have demonstrated relationships between biologically active extracellular matrix components, or matrikines, and COPD pathogenesis. We studied the relationships between the matrikine acetyl-proline-glycine-proline (AcPGP) in sputum and plasma and clinical features of COPD.

Methods

Sputum and plasma samples were obtained from COPD participants in the SPIROMICS cohort at enrollment. AcPGP was isolated using solid phase extraction and measured by mass spectrometry. Demographics, spirometry, quality of life questionnaires, and quantitative computed tomography (CT) imaging with parametric response mapping (PRM) were obtained at baseline. Severe COPD exacerbations were recorded at 1-year of prospective follow-up. We used linear and logistic regression models to measure associations between AcPGP and features of COPD, and Kaplan-Meier analyses to measure time-to-first severe exacerbation.

Results

The 182 COPD participants in the analysis were 66 ± 8 years old, 62% male, 84% White race, and 39% were current smokers. AcPGP concentrations were 0.61 ± 1.89 ng/mL (mean ± SD) in sputum and 0.60 ± 1.13 ng/mL in plasma. In adjusted linear regression models, sputum AcPGP was associated with FEV1/FVC, spirometric GOLD stage, PRM-small airways disease, and PRM-emphysema. Sputum AcPGP also correlated with severe AECOPD, and elevated sputum AcPGP was associated with shorter time-to-first severe COPD exacerbation. In contrast, plasma AcPGP was not associated with symptoms, pulmonary function, or severe exacerbation risk.

Conclusions

In COPD, sputum but not plasma AcPGP concentrations are associated with the severity of airflow limitation, small airways disease, emphysema, and risk for severe AECOPD at 1-year of follow-up.

Trial registration

ClinicalTrials.gov: NCT01969344 (SPIROMICS).
Repeated mosquito net distributions, improved treatment, and trends in malaria cases in sentinel health facilities in Papua New Guinea
Authors: Rodriguez-Rodriguez Daniela , Maraga Seri , Lorry Lina , Robinson Leanne J. , Siba Peter M. , Mueller Ivo , Pulford Justin , Ross Amanda , Hetzel Manuel W.
Published: November 2019

Background

Long-lasting insecticidal nets (LLIN), improved diagnosis and artemisinin-based combination therapy (ACT) have reduced malaria prevalence in Papua New Guinea since 2008. Yet, national incidence trends are inconclusive due to confounding effects of the scale-up of rapid diagnostic tests, and inconsistencies in routine reporting.

Methods

Malaria trends and their association with LLIN and ACT roll-out between 2010 and 2014 in seven sentinel health facilities were analysed. The analysis included 35,329 fever patients. Intervention effects were estimated using regression models.

Results

Malaria incidence initially ranged from 20 to 115/1000 population; subsequent trends varied by site. Overall, LLIN distributions had a cumulative effect, reducing the number of malaria cases with each round (incidence rate ratio ranging from 0.12 to 0.53 in five sites). No significant reduction was associated with ACT introduction.Plasmodium falciparumremained the dominant parasite in all sentinel health facilities. Resurgence occurred in one site in which a shift to early and outdoor biting of anophelines had previously been documented.

Conclusions

LLINs, but not ACT, were associated with reductions of malaria cases in a range of settings, but sustainability of the gains appear to depend on local factors. Malaria programmes covering diverse transmission settings such as Papua New Guinea must consider local heterogeneity when choosing interventions and ensure continuous monitoring of trends.
Clinical implication of disturbed left atrial phasic functions in the heterogeneous population associated with hypertension or atrial fibrillation
Authors: Zhu Mengruo , Chen Haiyan , Liu Yang , Shu Xianhong
Published: November 2019

Background

To evaluate left atrial (LA) phasic functions in patients with hypertension and/or paroxysmal atrial fibrillation (PAF) and its clinical significance.

Methods

LA strain was studied in 77 patients (25 hypertension, 24 lone AF, and 28 with both hypertension and PAF) and 28 controls using two-dimensional speckle-tracking echocardiography (2D STE). The following indexes during atrial reservoir, conduit and pump phase were analyzed respectively: (1) peak atrial longitudinal strain (PALS) and strain rate (PALSR), (2) the standard deviation of time to PALS and PALSR of all LA segments (TpS-SD% and TpSR-SD%).

Results

Compared with controls, PALSres, PALScond and PALSRcond were significantly reduced in patients with isolated hypertension (all P < 0.01) but no significant differences were observed in PALSpump, PALSRpump and TpSpump-SD% between them (all P > 0.05). PALSpump, PALSRpump and PALSRres were significantly lower in patients with both hypertension and PAF than in those with isolated hypertension (all P < 0.05). PALS and PALSR were significantly decreased, and TpS-SD% was significantly increased during each phase in lone AF patients than in controls (all P < 0.05), and PALSRpump was further depressed in patients with both hypertension and PAF (P = 0.029). PALSRcond ≤ 1.475 s− 1 combined with TpSpump-SD% ≥ 3.25% (sensitivity, 85%; specificity, 71%; AUC = 0.845, P < 0.001) could distinguish lone AF from healthy subjects effectively, while in hypertensive patients, PALSpump ≤ 14.2% was found to be an independent differentiator for occurrence of AF or not with sensitivity of 81% and specificity of 84% (AUC = 0.838, P < 0.001). LAVI≥29.3 mL/m2 was an independent characteristic for reflecting different LA remodeling in lone AF or hypertension with AF.

Conclusions

The impairment of LA phasic functions was varied in patients with hypertension and/or AF. The disturbed LA phasic functions were proved to have independent abilities of differential diagnosis in this heterogeneous population associated with hypertension or AF.
Value of preoperative ultrasound in evaluating the peritoneal cancer index of pseudomyxoma peritonei
Authors: Liang Lei , Wang Wenhai , Zhou Nan , Guo Jun , Lu Yiyan , Xu Hongbin , Zhang Shutian
Published: November 2019

Purpose

This study aimed to explore the value of preoperative ultrasonography (US) in evaluating the peritoneal cancer index (PCI) of pseudomyxoma peritonei (PMP).

Methods

An ultrasound examination was performed on 59 patients with PMP before surgery, and the ultrasound PCI was evaluated. The accuracy of ultrasound PCI score was evaluated with the surgical PCI score as the gold standard.

Results

The preoperative ultrasound PCI was compared with the surgical PCI. The Spearman correlation coefficient of the total PCI score was 0.608 (P < 0.05). The difference in the Spearman correlation coefficient between the preoperative ultrasound PCI and the surgical PCI in areas 0–7 was statistically significant. (1) Among them, the total score and the correlation between 0–3 and 6 were higher. (2) Compared with the surgical PCI, overestimation (> 20%) was concentrated mainly in areas 2 and 4–8 for 2 points, and underestimation (< 20%) was concentrated mainly in areas 1, 3, 4, and 8 for 3 points. (3) The sensitivity and specificity of preoperative ultrasound for predicting the presence or absence of lesions were 85.7% and 50.0%, respectively. The sensitivity of LS 1, LS 2, and LS 3 was 31.7%, 48.2%, and 71.0%, respectively, and the specificity was 44.8%, 55.3%, and 58.8%, respectively.

Conclusion

The ultrasound examination can be used to score the preoperative PCI, judge the severity, and predict the prognosis in patients with PMP.
Mouse-adapted H9N2 avian influenza virus causes systemic infection in mice
Authors: Hu Zhe , Zhang Yiran , Wang Zhen , Wang Jingjing , Tong Qi , Wang Mingyang , Sun Honglei , Pu Juan , Liu Changqing , Liu Jinhua , Sun Yipeng
Published: November 2019

Background

H9N2 influenza viruses continuously circulate in multiple avian species and are repeatedly transmitted to humans, posing a significant threat to public health. To investigate the adaptation ability of H9N2 avian influenza viruses (AIVs) to mammals and the mutations related to the host switch events, we serially passaged in mice two H9N2 viruses of different HA lineages — A/Quail/Hong Kong/G1/97 (G1) of the G1-like lineage and A/chicken/Shandong/ZB/2007 (ZB) of the BJ/94-like lineage —and generated two mouse-adapted H9N2 viruses (G1-MA and ZB-MA) that possessed significantly higher virulence than the wide-type viruses.

Finding

ZB-MA replicated systemically in mice. Genomic sequence alignment revealed 10 amino acid mutations coded by 4 different gene segments (PB2, PA, HA, and M) in G1-MA compared with the G1 virus and 23 amino acid mutations in 5 gene segments (PB1, PA, HA, M, and NS) in ZB-MA compared to ZB virus, indicating that the mutations in the polymerase, HA, M, and NS genes play critical roles in the adaptation of H9N2 AIVs to mammals, especially, the mutations of M1-Q198H and M1-A239T were shared in G1-MA and ZB-MA viruses. Additionally, several substitutions showed a higher frequency in human influenza viruses compared with avian viruses.

Conclusions

Different lineages of H9N2 could adapt well in mice and some viruses could gain the ability to replicate systemically and become neurovirulent. Thus, it is essential to pay attention to the mammalian adaptive evolution of the H9N2 virus.
Heparin sulfate is the attachment factor of duck Tembus virus on both BHK21 and DEF cells
Authors: Wu Shaoxiong , Wu Zhen , Wu Yuanyuan , Wang Tao , Wang Mingshu , Jia Renyong , Zhu Dekang , Liu Mafeng , Zhao Xinxin , Yang Qiao , Wu Ying , Zhang Shaqiu , Liu Yunya , Zhang Ling , Yu Yanling , Pan Leichang , Chen Shun , Cheng Anchun
Published: November 2019

Background

Duck tembusu virus (DTMUV, genus Flaviviruses, family Flaviviridae) is an emerging flavivirus that can infect a wide range of cells and cell lines in vitro, though the initial step of virus invasion remains obscure.

Methods

In this study, drug treatments that including heparin, chondroitin sulfate, heparinase I, chondroitinase ABC and trypsin were applied to detect the influence of DTMUV absorption, subsequently, the copy number of viral genome RNA was analyzed by quantitative real-time PCR. The inhibition process of viral absorption or entry by heparin was determined by western blotting, and the cytotoxicity of drug treated cells was detected by cell counting kit-8.

Results

We found that the desulfation of glycosaminoglycans (GAGs) with sodium chlorate had a significant effect on the adsorption of DTMUV in both BHK21 and DEF cells. Based on this result, we incubated cells with a mixture of DTMUV and GAGs competition inhibitors or pre-treated cells with inhibitors, after incubation with the virus, the NS5 expression of DTMUV and viral titers were detected. The data suggested that heparin can significantly inhibit the absorption of DTMUV in a dose dependent manner but not at the step of viral entry in BHK21 and DEF cells. Meanwhile, heparinase I can significantly inhibit DTMUV attachment step.

Conclusions

Our results clearly proved that heparin sulfate plays an important role in the first step of DTMUV entry, viral attachment, in both BHK21 and DEF cells, which sheds light on the entry mechanism of DTMUV.
Survival benefits of hypofractionated radiotherapy combined with temozolomide or temozolomide plus bevacizumab in elderly patients with glioblastoma aged ≥ 75 years
Authors: Ohno Makoto , Miyakita Yasuji , Takahashi Masamichi , Igaki Hiroshi , Matsushita Yuko , Ichimura Koichi , Narita Yoshitaka
Published: November 2019

Background and purpose

The purpose of this study was to evaluate the outcomes of elderly patients (aged ≥75 years) with newly diagnosed glioblastoma (GBM), who were treated with hypofractionated radiotherapy comprising 45 Gy in 15 fractions combined with temozolomide (TMZ) or TMZ and bevacizumab (TMZ/Bev).

Materials and methods

Between October 2007 and August 2018, 30 patients with GBM aged ≥75 years were treated with hypofractionated radiotherapy consisting of 45 Gy in 15 fractions. Twenty patients received TMZ and 10 received TMZ/Bev as upfront chemotherapy. O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation status was analyzed by pyrosequencing. The cutoff value of the mean level of methylation at the 16 CpG sites was 16%.

Results

Median overall survival (OS) and progression-free survival (PFS) were 12.9 months and 9.9 months, respectively. The 1-year OS and PFS rates were 64.7 and 34.7%, respectively. Median OS and PFS did not differ significantly between patients with MGMT promoter hypermethylation (N = 11) and those with hypomethylation (N = 16) (17.4 vs. 11.8 months, p = 0.32; and 13.1 vs. 7.3 months, p = 0.11, respectively). The median OS and PFS were not significantly different between TMZ (N = 20) and TMZ/Bev (N = 10) chemotherapy (median OS: TMZ 12.9 months vs. TMZ/Bev 14.6 months, p = 0.93, median PFS: TMZ 8.5 months vs TMZ/Bev 10.0 months, p = 0.64, respectively). The median time until Karnofsky performance status (KPS) score decreasing below 60 points was 7.9 months. The best radiological responses included 11 patients with a partial response (36.7%). Grade 3/4 toxicities included leukopenia in 15 patients (50%), anorexia in 4 (13.3%), and hyponatremia during concomitant chemotherapy in 3 (10%).

Conclusion

Our hypofractionated radiotherapy regimen combined with TMZ or TMZ/Bev showed benefits in terms of OS, PFS, and KPS maintenance with acceptable toxicities in elderly patients with GBM aged ≥75 years.