bluuebunny/crossref_metadata_2025 huggingface dataset:
Could a multidisciplinary regional audit identify avoidable factors and delays that contribute to stillbirths? A retrospective cohort study
Authors: Sterpu I. , Bolk J. , Perers Öberg S. , Hulthén Varli I. , Wiberg Itzel E.
Published: November 2020

Background

The annual rate of stillbirth in Sweden has remained largely unchanged for the past 30 years. In Sweden, there is no national audit system for stillbirths. The aim of the study was to determine if a regional multidisciplinary audit could help in identifying avoidable factors and delays associated with stillbirths.

Methods

Population-based retrospective cohort study.

Settings: Six labour wards in Stockholm County.

Participants: Women delivering a stillbirth > 22 weeks of gestation in Stockholm during 2017.

Intervention: A multidisciplinary team was convened. Each team member independently assessed the medical chart of each case of stillbirth regarding causes and preventability, level of delay, the standard of healthcare provided, the investigation of maternal/foetal diseases and if any recommendations were given for the next pregnancy. A decision was based on the agreement of all five members. If no agreement was reached, a reassessment of the case was done and the medical record was scrutinized again until a mutual decision was made.

Primary outcomes: The frequency of probably/possibly preventable factors associated with a stillbirth and the level of delay (patient/caregiver).

Secondary outcomes: The causes of death, the standard of antenatal/intrapartum/postpartum care, whether a summary of possible causes of the stillbirth was made and if any plans for future pregnancies were noted.

Results

Thirty percent of the stillbirths were assessed as probably/possibly preventable. More frequent ultrasound/clinical check-ups, earlier induction of labour and earlier interventions in line with current guidelines were identified as possibly preventable factors. A possibly preventable stillbirth was more common among non-Swedish-speaking women (p = 0.03). In 15% of the cases, a delay by the healthcare system was identified. Having multiple caregivers, absence of continuity in terms of attending the antenatal clinic and not following the basic monitoring program for antenatal care were also identified as risk factors for a delay.

Conclusion

A national/regional multidisciplinary audit group retrospectively identified factors associated with stillbirth. Access to good translation services or a more innovative approach to the problem regarding communication with mothers could be an important factor to decrease possible patient delays contributing to stillbirths.

Trial registration

NCT04281368.
Accumulation of the delivered dose based on cone-beam CT and deformable image registration for non-small cell lung cancer treated with hypofractionated radiotherapy
Authors: Wang Bin , Wang Da Quan , Lin Mao Sheng , Lu Shi Pei , Zhang Jun , Chen Li , Li Qi Wen , Cheng Zhang Kai , Liu Fang Jie , Guo Jin Yu , Liu Hui , Qiu Bo
Published: November 2020

Background

This study aimed to quantify the dosimetric differences between the planned and delivered dose to tumor and normal organs in locally advanced non-small cell lung cancer (LANSCLC) treated with hypofractionated radiotherapy (HRT), and to explore the necessity and identify optimal candidates for adaptive radiotherapy (ART).

Methods

Twenty-seven patients with stage III NSCLC were enrolled. Planned radiation dose was 51Gy in 17 fractions with cone-beam CT (CBCT) acquired at each fraction. Virtual CT was generated by deformable image registration (DIR) of the planning CT to CBCT for dose calculation and accumulation. Dosimetric parameters were compared between original and accumulated plans using Wilcoxon signed rank test. Correlations between dosimetric differences and clinical variables were analyzed using Mann-Whitney U test or Chi-square test.

Results

Patients had varied gross tumor volume (GTV) reduction by HRT (median reduction rate 11.1%, range − 2.9-44.0%). The V51 of planning target volume for GTV (PTV-GTV) was similar between original and accumulated plans (mean, 88.2% vs. 87.6%, p = 0.452). Only 11.1% of patients had above 5% relative decrease in V51 of PTV-GTV in accumulated plans. Compared to the original plan, limited increase (median relative increase < 5%) was observed in doses of total lung (mean dose, V20 and V30), esophagus (mean dose, maximum dose) and heart (mean dose, V30 and V40) in accumulated plans. Less than 30% of patients had above 5% relative increase of lung or heart doses. Patients with quick tumor regression or baseline obstructive pneumonitis showed more notable increase in doses to normal structures. Patients with baseline obstructive atelectasis showed notable decrease (10.3%) in dose coverage of PTV-GTV.

Conclusions

LANSCLC patients treated with HRT had sufficient tumor dose coverage and acceptable normal tissue dose deviation. ART should be applied in patients with quick tumor regression and baseline obstructive pneumonitis/atelectasis to spare more normal structures.
Clinical evaluation of toric intraocular lens implantation based on iTrace wavefront keratometric astigmatism
Authors: Zhang Zhe , Li Hui , Zhou Jing , Zhang Yaqin , Zhang Suhua
Published: November 2020

Background

Currently, there is no standard technique for determining corneal astigmatism. The iTrace wavefront aberrometry of cornea calculated steep power and axis based on the best Zernike mathematical fit from all topo data within 4 mm circle. It was supposed to be more accurate than iTrace simulated keratometry which was calculated based on only 4 points on the circle of 3 mm. This aim of this study was to evaluate visual outcomes and rotational stability after toric intraocular lens (IOL) implantation using the wavefront aberrometry of the cornea with iTrace.

Setting: Single site in China, Shanxi Eye Hospital, Shanxi, China.

Design: Prospective case series.

Methods

The study included 85 eyes of 63 patients undergoing phacoemulsification and toric IOL implantation. The IOL power and cylinders were chosen with the help of the iTrace toric planning program using wavefront keratometric astigmatism. Astigmatic changes were assessed using Alpins vector method over a 3-month follow-up period.

Results

Preoperative mean corneal topographic astigmatism was 1.91 diopters (D) ± 0.69 (standard deviation). Postoperative mean refractive astigmatism decreased significantly to 0.48 D ± 0.34. Surgical induced astigmatism was 1.73 D ± 0.77 and the mean correction index was 0.89 ± 0.22, showing a slight undercorrection. The proportion of astigmatism ≤0.50 D increased from 0 to 71.8% postoperatively.

Conclusions

This is the first study on evaluation of clinical outcomes of toric IOL implantation in corneal astigmatism patients using iTrace wavefront keratometric readings. The findings show that use of iTrace built-in toric calculator is safe and effective for planning toric IOL surgery for wavefront keratometric astigmatism.

Trial registration

Current Controlled Trials ISRCTN94956424, Retrospectively registered (Date of registration: 05 February 2020).
The use of direct oral challenge to confirm allergies to penicillin class antibiotics in Danish children
Authors: Krusenstjerna-Hafstrøm Thomas , Rubak Sune
Published: November 2020

Background

A high number of children are referred to pediatric departments with a suspected allergic reaction to antibiotics. The prevalence of true allergy is considered to be significantly lower than shown from clinical history and symptoms alone. This study investigated the historical use of direct oral challenges at three specialist pediatric departments in Denmark.

Methods

In this retrospective medical record review study, 141 children (69 boys and 72 girls) with a clinical history of suspected penicillin class allergy were investigated. A standardized questionnaire for drug allergy was completed in the beginning of the investigation, which also included a skin prick test (SPT), measurement of IgE to different types of penicillin, and a drug challenge (DC).

Results

Only four (2.8%) of the patients referred for further investigation in our study had a positive DC. We found no correlation between a positive DC, positive SPT or elevated specific IgE. None of the patients with a positive DC reacted with a rash alone prior to investigation.

Conclusions

Allergy to penicillin in children is rare and probably overestimated. In children reacting to penicillin with a rash alone, our study indicated that the rash was probably not related to allergy and treatment should thus be continued.
Modeling the impact of school reopening on SARS-CoV-2 transmission using contact structure data from Shanghai
Authors: Lee Benjamin , Hanley John P. , Nowak Sarah , Bates Jason H. T. , Hébert-Dufresne Laurent
Published: November 2020

Background

Mathematical modeling studies have suggested that pre-emptive school closures alone have little overall impact on SARS-CoV-2 transmission, but reopening schools in the background of community contact reduction presents a unique scenario that has not been fully assessed.

Methods

We adapted a previously published model using contact information from Shanghai to model school reopening under various conditions. We investigated different strategies by combining the contact patterns observed between different age groups during both baseline and “lockdown” periods. We also tested the robustness of our strategy to the assumption of lower susceptibility to infection in children under age 15 years.

Results

We find that reopening schools for all children would maintain a post-intervention R0 < 1 up to a baseline R0 of approximately 3.3 provided that daily contacts among children 10–19 years are reduced to 33% of baseline. This finding was robust to various estimates of susceptibility to infection in children relative to adults (up to 50%) and to estimates of various levels of concomitant reopening in the rest of the community (up to 40%). However, full school reopening without any degree of contact reduction in the school setting returned R0 virtually back to baseline, highlighting the importance of mitigation measures.

Conclusions

These results, based on contact structure data from Shanghai, suggest that schools can reopen with proper precautions during conditions of extreme contact reduction and during conditions of reasonable levels of reopening in the rest of the community.
Predictors and burden of injury mortality in the Thai cohort study 2005–2015
Authors: Lowe C. T. , Kelly M. , Seubsman S. , Sleigh A.
Published: November 2020

Background

Thailand is a high injury burden setting. In 2015 it had the world’s second highest rate of road traffic fatalities. In order to develop strategies to reduce this burden an accurate understanding of the development of injury risk over the life course is essential.

Methods

A national cohort of adult Thais was recruited in 2005 (n = 87,151). Participants completed a health questionnaire covering geodemographic, behavioural, health and injury data. Citizen ID numbers were matched with death registration records, identifying deaths from any injury. Adjusted logistic regression models were used to measure associations between baseline exposures and injury deaths between 2005 and 2015.

Results

Injury mortality comprised 363 individuals, the majority (36%) from traffic injuries. Predictors of all-injury mortality were being male (AOR 3.55, 95% CI 2.57–4.89), Southern Thai (AOR 1.52, 95% CI 1.07–2.16), smoking (AOR 1.55, 95% CI 1.16–2.17), depression (AOR 1.78, 95% CI 1.07–2.96), previous injury (AOR 1.37, 95% CI 1.03–1.81) and drink driving history (AOR 1.37, 95%CI 1.02–1.85). Age and region of residence were stronger predictors for men, while anxiety/depression was a stronger predictor for women. Among males in the far south, assault caused the largest proportion of injury mortality, elsewhere traffic injury was most common.

Conclusions

This study identifies that a history of drink driving, but not regular alcohol consumption, increased injury risk. The associations between smoking and depression, and injury mortality also need further consideration.
COVID-19 precautionary behavior: the Israeli case in the initial stage of the outbreak
Authors: Shinan-Altman Shiri , Levkovich Inbar
Published: November 2020

Background

The lay public’s behavioral responses during a virus spread, such as the COVID-19, play an important role in bringing the outbreak under control, and provide insights into development of risk communication messages to the public. Therefore, this study aimed to explore the association between knowledge about COVID-19, perceived susceptibility, emotional reactions and precautionary behavior among the Israeli lay public at the beginning of the COVID-19 outbreak.

Method

A cross-sectional study was conducted among 1407 participants, aged 18 + .

Participants completed measures of knowledge about COVID-19, perceived susceptibility, emotional reactions, precautionary behavior, and socio-demographic questionnaires. A hierarchical regression model was calculated with precautionary behavior as the dependent variable.

Results

Findings indicated that precautionary behavior was higher for females, older participants, participants with higher levels of knowledge about COVID-19, and participants with greater negative emotional reactions. A negative curvilinear relationship was found between perceived susceptibility and precautionary behavior, so that the latter was highest for participants with moderate perceived susceptibility. All interaction terms were non-significant.

Conclusions

Findings suggest that in order to enhance precautionary behavior in the initial stage of a virus outbreak, it is recommended to pay attention to the public’s knowledge about the virus, perceived susceptibility and emotional reactions. Although negative feelings about the virus may motivate preventive behavior, it is important to address these feelings.
Elevated serum matrix metalloprotease (MMP-2) as a candidate biomarker for stable COPD
Authors: Mahor Durga , Kumari Vandana , Vashisht Kapil , Galgalekar Ruma , Samarth Ravindra M. , Mishra Pradyumna K. , Banerjee Nalok , Dixit Rajnikant , Saluja Rohit , De Sajal , Pandey Kailash C.
Published: November 2020

Background

The increasing trend of Chronic Obstructive Pulmonary Disease (COPD) in becoming the third leading cause of deaths by 2020 is of great concern, globally as well as in India. Dysregulation of protease/anti-protease balance in COPD has been reported to cause tissue destruction, inflammation and airway remodelling; which are peculiar characteristics of COPD. Therefore, it is imperative to explore various serum proteases involved in COPD pathogenesis, as candidate biomarkers. COPD and Asthma often have overlapping symptoms and therefore involvement of certain proteases in their pathogenesis would render accurate diagnosis of COPD to be difficult.

Methods

Serum samples from controls, COPD and Asthma patients were collected after requisite institutional ethics committee approvals. The preliminary analysis qualitatively and quantitatively analyzed various serum proteases by ELISA and mass spectrometry techniques. In order to identify a distinct biomarker of COPD, serum neutrophil elastase (NE) and matrix metalloprotease-2 (MMP-2) from COPD and Asthma patients were compared; as these proteases tend to have overlapping activities in both the diseases. A quantitative analysis of the reactive oxygen species (ROS) in the serum of controls and COPD patients was also performed. Statistical analysis for estimation of p-values was performed using unpaired t-test with 95% confidence interval.

Results

Amongst the significantly elevated proteases in COPD patients vs the controls- neutrophil elastase (NE) [P < 0.0241], caspase-7 [P < 0.0001] and matrix metalloprotease-2 (MMP-2) [P < 0.0001] were observed, along with increased levels of reactive oxygen species (ROS) [P < 0.0001]. The serum dipeptidyl peptidase-IV (DPP-IV) [P < 0.0010) concentration was found to be decreased in COPD patients as compared to controls. Interestingly, a distinct elevation of MMP-2 was observed only in COPD patients, but not in Asthma, as compared to controls. Mass spectrometry analysis further identified significant alterations (fold-change) in various proteases (carboxy peptidase, MMP-2 and human leukocyte elastase), anti-proteases (Preg. zone protein, α-2 macroglobulin, peptidase inhibitor) and signalling mediators (cytokine suppressor- SOCS-3).

Conclusion

The preliminary study of various serum proteases in stable COPD patients distinctly identified elevated MMP-2 as a candidate biomarker for COPD, subject to its validation in large cohort studies.
Correlation between sestrin2 expression and airway remodeling in COPD
Authors: Zhang Da-Wei , Wei Yuan-Yuan , Ji Shuang , Fei Guang-He
Published: November 2020

Background

Airway remodeling is a major pathological characteristic of chronic obstructive pulmonary disease (COPD), and has been shown to be associated with oxidative stress. Sestrin2 has recently drawn attention as an important antioxidant protein. However, the underlying correlation between sestrin2 and airway remodeling in COPD has yet to be clarified.

Methods

A total of 124 subjects were enrolled in this study, including 62 control subjects and 62 COPD patients. The pathological changes in airway tissues were assessed by different staining methods. The expression of sestrin2 and matrix metalloproteinase 9 (MMP9) in airway tissues was monitored by immunohistochemistry. Enzyme-linked immunosorbent assays (ELISAs) were used to detect the serum concentrations of sestrin2 and MMP9. The airway parameters on computed tomography (CT) from all participants were measured for evaluating airway remodeling. The relationship between serum sestrin2 and MMP9 concentration and airway parameters in chest CT was also analyzed.

Results

In patients with COPD, staining of airway structures showed distinct pathological changes of remodeling, including cilia cluttered, subepithelial fibrosis, and reticular basement membrane (Rbm) fragmentation. Compared with control subjects, the expression of sestrin2 and MMP9 was significantly increased in both human airway tissues and serum. Typical imaging characteristics of airway remodeling and increased airway parameters were also found by chest CT. Additionally, serum sestrin2 concentration was positively correlated with serum MMP9 concentration and airway parameters in chest CT.

Conclusion

Increased expression of sestrin2 is related to airway remodeling in COPD. We demonstrated for the first time that sestrin2 may be a novel biomarker for airway remodeling in patients with COPD.
Rapidly progressive metastatic cholangiocarcinoma in a postpartum patient with cystic fibrosis: a case report
Authors: Carson Sara W. , Craven Kelly E. , Nauen David , Montemayor Kristina , Yarchoan Mark , Burns William R. , Merlo Christian A. , West Natalie E.
Published: November 2020

Background

Cholangiocarcinoma is a rare gastrointestinal malignancy that arises within the intrahepatic, perihilar, and/or extrahepatic bile ducts. Individuals with cystic fibrosis are at increased risk for gastrointestinal malignancies. The most common gastrointestinal malignancy in cystic fibrosis is colon cancer, but other gastrointestinal malignancies also occur at greater rates than the general population.

Case presentation

We present a case of a rapidly progressive metastatic intrahepatic cholangiocarcinoma in an individual with cystic fibrosis who was 5 months postpartum, incidentally found while undergoing a lung transplantation evaluation.

Conclusion

A heightened clinical awareness of gastrointestinal malignancies, beyond colon cancer, in individuals with cystic fibrosis is warranted. It remains unclear if pregnancy is an additional risk factor for gastrointestinal malignancies in cystic fibrosis.
Do future healthcare professionals have adequate knowledge about risk factors for stress urinary incontinence in women?
Authors: Witkoś Joanna , Hartman-Petrycka Magdalena
Published: November 2020

Background

Stress urinary incontinence worsens living conditions as far as the occupational, social, mental, physical and sexual aspects of a woman’s life. Despite its real impact on the everyday lives of millions of women around the world, this problem is still disregarded and treated only as a discomfort associated with personal hygiene. Could this be due to negligence on the part of medical personnel in this matter and perhaps this lack of knowledge and proper information intended for women with stress urinary incontinence? Implementing educational activities to increase knowledge about urinary incontinence will translate into better educated women and earlier implementation of urinary incontinence treatment in the future. To properly educate women at risk of urinary incontinence, one needs to be familiar with the condition, in particular the risk factors for its development. The purpose of the study was to evaluate the degree of knowledge of students graduating from medical faculties have regarding risk factors for stress urinary incontinence in women and assess where the students’ knowledge of this problem came from.

Methods

The research involved 1581 final year students of medical faculties: nursing and midwifery (258), medicine (432), physiotherapy (402) and other medical (489). The author’s survey was used for the research. The chi2 test was used for analysis.

Results

Students in faculties of nursing and midwifery, general medicine, physiotherapy, and other medical faculties could correctly list stress urinary incontinence risk factors in 88.8%, 81.7%, 74.4% and 51.9% of their answers respectively (p < 0.01). The most frequently mentioned source of knowledge about stress urinary incontinence was higher level education in 82.6%, 89.8%, 90.0% and 34.4% of the respective groups’ replies (p < 0.001).

Conclusions

Nursing and midwifery students had the greatest theoretical knowledge of stress urinary incontinence, and lesser knowledge was found among general medicine students, while physiotherapy students and students of other medical faculties had the least theoretical knowledge about risk factors for urinary incontinence. It is advisable that more emphasis be placed on educating students about stress urinary incontinence due to their insufficient knowledge, in particular for future doctors and physiotherapists who will have direct contact with patients.
A comparative study of dementia knowledge, attitudes and care approach among Chinese nursing and medical students
Authors: Wang Yao , Xiao Lily Dongxia , Huang Rong
Published: November 2020

Background

Dementia care requires inter-disciplinary collaboration starting from formal health professional education. Yet, little is known about how undergraduate medical and nursing students perceive dementia care in China. The aim of this study was to investigate undergraduate medical and nursing students’ dementia knowledge, attitudes and care approach in China.

Methods

A cross-sectional survey was conducted. Students enrolled in a 5-year Bachelor of Medicine Program and a 4-year Bachelor of Nursing Program from four universities with campuses across Eastern, Western, Southern and Northern China were recruited into the study. Three validated instruments, Alzheimer’s Disease Knowledge Scale (ADKS), Dementia Care Attitude Scale (DCAS) and Approach to Advanced Dementia Care Questionnaire (ADCQ), were used to examine students’ dementia knowledge, attitudes and perceived care approach. Data were collected using a self-administered survey.

Results

The number of medical and nursing students completing the survey was 526 and 467 respectively. Students’ overall knowledge about dementia was poor, but attitudes were generally positive. The overall mean score of students’ dementia knowledge examined by the ADKS was 19.49 (SD = 2.82) out of 30, students’ attitudes to dementia was 29.92(SD = 3.35) out of 40, and students’ person-centred care approach of dementia was 5.42 (SD = 2.20) out of 13. Medical students demonstrated higher dementia knowledge scores and showed less positive attitude scores than nursing students (p < 0.05). Students would not apply a person-centred care approach. There were no statistically significant differences in the mean scores of ADCQ between nursing students and medical students.

Conclusions

Study results highlight the urgent need to implement an inter-disciplinary approach to increasing dementia education among Chinese medical and nursing students, and ensuring that students have adequate knowledge, attitudes and experience in the care of people with dementia.
Protein kinase A controls yeast growth in visible light
Authors: Molin Mikael , Logg Katarina , Bodvard Kristofer , Peeters Ken , Forsmark Annabelle , Roger Friederike , Jörhov Anna , Mishra Neha , Billod Jean-Marc , Amir Sabiha , Andersson Mikael , Eriksson Leif A. , Warringer Jonas , Käll Mikael , Blomberg Anders
Published: November 2020

Background

A wide variety of photosynthetic and non-photosynthetic species sense and respond to light, having developed protective mechanisms to adapt to damaging effects on DNA and proteins. While the biology of UV light-induced damage has been well studied, cellular responses to stress from visible light (400–700 nm) remain poorly understood despite being a regular part of the life cycle of many organisms. Here, we developed a high-throughput method for measuring growth under visible light stress and used it to screen for light sensitivity in the yeast gene deletion collection.

Results

We found genes involved in HOG pathway signaling, RNA polymerase II transcription, translation, diphthamide modifications of the translational elongation factor eEF2, and the oxidative stress response to be required for light resistance. Reduced nuclear localization of the transcription factor Msn2 and lower glycogen accumulation indicated higher protein kinase A (cAMP-dependent protein kinase, PKA) activity in many light-sensitive gene deletion strains. We therefore used an ectopic fluorescent PKA reporter and mutants with constitutively altered PKA activity to show that repression of PKA is essential for resistance to visible light.

Conclusion

We conclude that yeast photobiology is multifaceted and that protein kinase A plays a key role in the ability of cells to grow upon visible light exposure. We propose that visible light impacts on the biology and evolution of many non-photosynthetic organisms and have practical implications for how organisms are studied in the laboratory, with or without illumination.
Identification of intestinal flora-related key genes and therapeutic drugs in colorectal cancer
Authors: Zhang Jiayu , Zhang Huaiyu , Li Faping , Song Zheyu , Li Yezhou , Zhao Tiancheng
Published: November 2020

Background

Colorectal cancer (CRC) is a multifactorial tumor and a leading cause of cancer-specific deaths worldwide. Recent research has shown that the alteration of intestinal flora contributes to the development of CRC. However, the molecular mechanism by which intestinal flora influences the pathogenesis of CRC remains unclear. This study aims to explore the key genes underlying the effect of intestinal flora on CRC and therapeutic drugs for CRC.

Methods

Intestinal flora-related genes were determined using text mining. Based on The Cancer Genome Atlas database, differentially expressed genes (DEGs) between CRC and normal samples were identified with the limma package of the R software. Then, the intersection of the two gene sets was selected for enrichment analyses using the tool Database for Annotation, Visualization and Integrated Discovery. Protein interaction network analysis was performed for identifying the key genes using STRING and Cytoscape. The correlation of the key genes with overall survival of CRC patients was analyzed. Finally, the key genes were queried against the Drug-Gene Interaction database to find drug candidates for treating CRC.

Results

518 genes associated with intestinal flora were determined by text mining. Based on The Cancer Genome Atlas database, we identified 48 DEGs associated with intestinal flora, including 25 up-regulated and 23 down-regulated DEGs in CRC. The enrichment analyses indicated that the selected genes were mainly involved in cell–cell signaling, immune response, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathway. The protein–protein interaction network was constructed with 13 nodes and 35 edges. Moreover, 8 genes in the significant cluster were considered as the key genes and chemokine (C-X-C motif) ligand 8 (CXCL8) correlated positively with the overall survival of CRC patients. Finally, a total of 24 drugs were predicted as possible drugs for CRC treatment using the Drug-Gene Interaction database.

Conclusions

These findings of this study may provide new insights into CRC pathogenesis and treatments. The prediction of drug-gene interaction is of great practical significance for exploring new drugs or novel targets for existing drugs.
A prognostic model for elderly patients with squamous non-small cell lung cancer: a population-based study
Authors: Chen Siying , Gao Chunxia , Du Qian , Tang Lina , You Haisheng , Dong Yalin
Published: November 2020

Background

Squamous cell carcinoma (SCC) is a main pathological type of non-small cell lung cancer. It is common among elderly patients with poor prognosis. We aimed to establish an accurate nomogram to predict survival for elderly patients (≥ 60 years old) with SCC based on the Surveillance, Epidemiology, and End Results (SEER) database.

Methods

The gerontal patients diagnosed with SCC from 2010 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. The independent prognostic factors were identified using multivariate Cox proportional hazards regression analysis, which were utilized to conduct a nomogram for predicting survival. The novel nomogram was evaluated by Concordance index (C-index), calibration curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA).

Results

32,474 elderly SCC patients were included in the analysis, who were randomly assigned to training cohort (n = 22,732) and validation cohort (n = 9742). The following factors were contained in the final prognostic model: age, sex, race, marital status, tumor site, AJCC stage, surgery, radiation and chemotherapy. Compared to AJCC stage, the novel nomogram exhibited better performance: C-index (training group: 0.789 vs. 0.730, validation group: 0.791 vs. 0.733), the areas under the receiver operating characteristic curve of the training set (1-year AUC: 0.846 vs. 0.791, 3-year AUC: 0.860 vs. 0.801, 5-year AUC: 0.859 vs. 0.794) and the validation set (1-year AUC: 0.846 vs. 0.793, 3-year AUC: 0.863 vs. 0.806, 5-year AUC: 0.866 vs. 0.801), and the 1-, 3- and 5-year calibration plots. Additionally, the NRI and IDI and 1-, 3- and 5-year DCA curves all confirmed that the nomogram was a great prognosis tool.

Conclusions

We constructed a novel nomogram that could be practical and helpful for precise evaluation of elderly SCC patient prognosis, thus helping clinicians in determining the appropriate therapy strategies for individual SCC patients.
Juvenile idiopathic arthritis fibroblast-like synoviocytes influence chondrocytes to alter BMP antagonist expression demonstrating an interaction between the two prominent cell types involved in endochondral bone formation
Authors: Simonds Megan M. , Schlefman Amanda R. , McCahan Suzanne M. , Sullivan Kathleen E. , Rose Carlos D. , Brescia AnneMarie C.
Published: November 2020

Background

To examine critical interactions between juvenile idiopathic arthritis synovial fibroblasts (JFLS) and chondrocytes (Ch), and their role in bony overgrowth seen in patients with juvenile idiopathic arthritis (JIA).

Methods

Control (CFLS) and JFLS were cultured in synoviocyte media containing recombinant BMP4. Ch were cultured in either CFLS or JFLS conditioned-media without stimulation. Media supernatants were analyzed by ELISA. RNA from conditioned media experiment was analyzed by ClariomS microarray.

Results

As expected, genes expressed in untreated JFLS and CFLS cultured in synoviocyte media were similar to each other and this expression differed from untreated Ch cultured in chondrocyte media. JFLS favor BMP ligand gene expression while downregulating TGFβ receptors’ expression. Noggin and chordin, antagonists with high affinity for BMP4, are JFLS- but not Ch-preferred regulators of BMP signaling. Compared to Ch, JFLS overexpress collagen X (COLX), a marker of chondrocyte hypertrophy. Exogenous BMP4 causes JFLS to significantly decrease expression of noggin and collagen II (COL2), a marker of chondrocyte proliferation, and causes overexpression of COLX and alkaline-phosphatase (ALP). Chondrocytes cultured in JFLS-conditioned media (Ch-JFLS) express BMP genes and favor chordin protein expression over other antagonists. Ch-JFLS have significantly increased expression of COL2 and significantly decreased expression of COLX.

Conclusions

These data suggest JFLS, in the presence of BMP4, undergo hypertrophy and that JFLS-conditioned media influence chondrocytes to become highly proliferative. To the authors’ knowledge, no prior study has shown that JFLS and chondrocytes play a direct role in the bony overgrowth in joints of patients with JIA and that BMPs or regulation of these growth factors influence the interaction between two prominent synovial cell types.
Metabolomic signatures for visceral adiposity and dysglycaemia in Asian Chinese and Caucasian European adults: the cross-sectional TOFI_Asia study
Authors: Wu Zhanxuan E. , Fraser Karl , Kruger Marlena C. , Sequeira Ivana R. , Yip Wilson , Lu Louise W. , Plank Lindsay D. , Murphy Rinki , Cooper Garth J. S. , Martin Jean-Charles , Poppitt Sally D.
Published: November 2020

Background

Asian Chinese are more susceptible to deposition of visceral adipose tissue (VAT) and type 2 diabetes (T2D) development than European Caucasians when matched for gender, age and body mass index (BMI). Our aims were: (i) characterise the ethnicity-specific metabolomic signature of visceral adiposity measured by dual energy X-ray absorptiometry (DXA) and fasting plasma glucose (FPG), and (ii) identify individuals susceptible to worse metabolic health outcomes.

Methods

Fasting plasma samples from normoglycaemic (n = 274) and prediabetic (n = 83) participants were analysed with liquid chromatography–mass spectrometry using untargeted metabolomics. Multiple linear regression adjusting for age, gender and BMI was performed to identify metabolites associated with FPG and VAT calculated as percentage of total body fat (%VATTBF) in each ethnic group. Metabolic risk groups in each ethnicity were stratified based on the joint metabolomic signature for FPG and %VATTBFand clinically characterised using partial least squares-discriminant analysis (PLS-DA) and t-tests.

Results

FPG was correlated with 40 and 110 metabolites in Caucasians and Chinese respectively, with diglyceride DG(38:5) (adjusted β = 0.29,p = 3.00E−05) in Caucasians and triglyceride TG(54:4) (adjusted β = 0.28,p = 2.02E−07) in Chinese being the most significantly correlated metabolite based on the p-value. %VATTBFwas correlated with 85 and 119 metabolites in Caucasians and Chinese respectively, with TG(56:2) (adjusted β = 0.3,p = 8.25E−09) in Caucasians and TG(58:3) (adjusted β = 0.25,p = 2.34E−08) in Chinese being the most significantly correlated. 24 metabolites associated with FPG were common to both ethnicities including glycerolipid species. 67 metabolites associated with %VATTBFwere common to both ethnicities including positive correlations with dihydroceramide, sphingomyelin, glycerolipid, phosphatidylcholine, phosphatidylethnolamine, and inverse correlations with ether-linked phosphatidylcholine. Participant re-stratification found greater total and central adiposity, worse clinical lipid profiles, higher serum glucoregulatory peptides and liver enzymes in normal fasting glucose (NFG) individuals with a prediabetic metabolomic profile than NFG individuals with a normoglycaemic metabolomic profile in both ethnicities.

Conclusions

Untargeted metabolomics identified common and disparate metabolites associated with FPG and %VATTBF, with an ethnic-dimorphic signature for these metabolic traits. These signatures could improve risk stratification and identify NFG individuals with an adverse cardiometabolic and T2D risk profile.
Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review
Authors: Onyango Calleb George , Ogonda Lilian , Guyah Bernard , Shiluli Clement , Ganda Gregory , Orang’o Omenge Elkanah , Patel Kirtika
Published: November 2020

Background

Cervical cancer screening is slowly transitioning from Pappanicolaou cytologic screening to primary Visual Inspection with Acetic Acid (VIA) or HPV testing as an effort to enhance early detection and treatment. However, an effective triage tests needed to decide who among the VIA or HPV positive women should receive further diagnostic evaluation to avoid unnecessary colposcopy referrals is still lacking. Evidence from experimental studies have shown potential usefulness of Squamous Cell Carcinoma Antigen (SCC Ag), Macrophage Colony Stimulating Factor (M-CSF), Vascular Endothelial Growth Factor (VEGF), MicroRNA, p16INKa / ki-67, HPV E6/E7/mRNA, and DNA methylation biomarkers in detecting premalignant cervical neoplasia. Given the variation in performance, and scanty review studies in this field, this systematic review described the diagnostic performance of some selected assays to detect high-grade cervical intraepithelial neoplasia (CIN2+) with histology as gold standard.

Methods

We systematically searched articles published in English between 2012 and 2020 using key words from PubMed/Medline and SCOPUS with two reviewers assessing study eligibility, and risk of bias. We performed a descriptive presentation of the performance of each of the selected assays for the detection of CIN2 + .

Results

Out of 298 citations retrieved, 58 articles were included. Participants with cervical histology yielded CIN2+ proportion range of 13.7–88.4%. The diagnostic performance of the assays to detect CIN2+ was; 1) SCC-Ag: range sensitivity of 78.6–81.2%, specificity 74–100%. 2) M-CSF: sensitivity of 68–87.7%, specificity 64.7–94% 3) VEGF: sensitivity of 56–83.5%, specificity 74.6–96%. 4) MicroRNA: sensitivity of 52.9–67.3%, specificity 76.4–94.4%. 5) p16INKa / ki-67: sensitivity of 50–100%, specificity 39–90.4%. 6) HPV E6/E7/mRNA: sensitivity of 65–100%, specificity 42.7–90.2%, and 7) DNA methylation: sensitivity of 59.7–92.9%, specificity 67–98%.

Conclusion

Overall, the reported test performance and the receiving operating characteristics curves implies that implementation of p16ink4a/ki-67 assay as a triage for HPV positive women to be used at one visit with subsequent cryotherapy treatment is feasible. For the rest of assays, more robust clinical translation studies with larger consecutive cohorts of women participants is recommended.
Health-care organization for the management and surveillance of SARS-CoV-2 infection in children during pandemic in Campania region, Italy
Authors: Nunziata Francesco , Bruzzese Eugenia , Poeta Marco , Pierri Luca , Catzola Andrea , Ciccarelli Gian Paolo , Vassallo Edoardo , Montella Emma , Lo Vecchio Andrea , Guarino Alfredo
Published: November 2020

Background

In comparison with adults, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection in children has a milder course. The management of children with suspected or confirmed coronavirus disease (COVID-19) needs to be appropriately targeted.

Methods

We designed a hub-and-spoke system to provide healthcare indications based on the use of telemedicine and stringent admission criteria, coordinate local stakeholders and disseminate information.

Result

Between March 24th and September 24th 2020, the Hub Centre managed a total of 208 children (52% males, median age, 5.2, IQR 2–9.6 years) with suspected or confirmed COVID-19. Among them, 174 were managed in cooperation with family pediatricians and 34 with hospital-based physicians. One hundred-four (50%) received a final diagnosis of SARS-CoV-2 infection. Application of stringent criteria for hospital admission based on clinical conditions, risk factors and respect of biocontainment measures, allowed to manage the majority of cases (74, 71.1%) through telemedicine. Thirty children (28%) were hospitalized (median length 10 days, IQR 5–19 days), mainly due to the presence of persistent fever, mild respiratory distress or co-infection occurring in infant or children with underlying conditions. However, the reasons for admission slightly changed over time.

Conclusion

An hub-and-spoke system is effective in coordinate territorial health-care structures involved in management paediatric COVID-19 cases through telemedicine and the definition of stringent hospital admission criteria.

The management of children with COVID-19 should be based on clinical conditions, assessed on a case-by-case critical evaluation, as well as on isolation measures, but may vary according to local epidemiological changes.
Molecular identification of native Wolbachia pipientis in Anopheles minimus in a low-malaria transmission area of Umphang Valley along the Thailand-Myanmar border
Authors: Tongkrajang Nongnat , Ruenchit Pichet , Tananchai Chatchai , Chareonviriyaphap Theeraphap , Kulkeaw Kasem
Published: November 2020

Background

Wolbachia, obligate intracellular bacteria, infect the majority of arthropods, including many mosquito species of medical importance. Some Wolbachia strains interfere with the development of Plasmodium parasites in female Anopheles, a major vector of malaria. The use of Wolbachia as a means to block malaria transmission is an emerging vector control strategy in highly endemic areas. Hence, identification of native Wolbachia strains in areas where malaria transmission is low may uncover a particular Wolbachia strain capable of Plasmodium interference. This study aims to identify native Wolbachia strains in female Anopheles spp. that are predominant in a low-malaria transmission area in mainland Southeast Asia.

Methods

Following a 2-year survey of malaria vectors in Umphang Valley of Tak Province, Thailand, DNA extracts of female An. minimus, An. peditaeniatus, and An. maculatus were subjected to amplification of the conserved region of the 16S rRNA-encoding gene. The DNA sequences of the amplicons were phylogenetically compared with those of known Wolbachia strains.

Results

Among three Anopheles spp., amplification was detected in only the DNA samples from An. minimus. The DNA sequencing of amplicons revealed 100% similarity to Wolbachia pipientis, confirming the specificity of amplification. The Wolbachia-positive An. minimus samples were devoid of Plasmodium 18S rRNA amplification. The phylogenetic trees indicate a close relationship with Wolbachia strains in subgroup B.

Conclusion

To the best of our knowledge, the data presented herein provide the first molecular evidence of a Wolbachia strain in An. minimus, hereinafter named wAnmi, in a low-malaria transmission area in the Umphang Valley of western Thailand. Further biological characterization is required to examine its potential for malaria transmission control in the field.

Graphical Abstract
Interchanging a limit and an integral: necessary and sufficient conditions
Authors: Kamihigashi Takashi
Published: November 2020

Let $\{f_{n}\}_{n \in \mathbb {N}}$

{

f
n

}

n
∈
N

be a sequence of integrable functions on a σ-finite measure space $(\Omega, \mathscr {F}, \mu )$
(
Ω
,
F
,
μ
)
. Suppose that the pointwise limit $\lim_{n \uparrow \infty } f_{n}$

lim

n
↑
∞

f
n

exists μ-a.e. and is integrable. In this setting we provide necessary and sufficient conditions for the following equality to hold: $$ \lim_{n \uparrow \infty } \int f_{n} \, d\mu = \int \lim_{n \uparrow \infty } f_{n} \, d\mu. $$

lim

n
↑
∞

∫

f
n

d
μ
=
∫

lim

n
↑
∞

f
n

d
μ
.
Identities involving 3-variable Hermite polynomials arising from umbral method
Authors: Raza Nusrat , Zainab Umme , Araci Serkan , Esi Ayhan
Published: November 2020

In this paper, we employ an umbral method to reformulate the 3-variable Hermite polynomials and introduce the 4-parameter 3-variable Hermite polynomials. We also obtain some new properties for these polynomials. Moreover, some special cases are discussed and some concluding remarks are also given.
Association of gut microbiota with metabolism in juvenile Atlantic salmon
Authors: Dvergedal H. , Sandve S. R. , Angell I. L. , Klemetsdal G. , Rudi K.
Published: November 2020

The gut microbiome plays a key role in animal health and metabolism through the intricate functional interconnection between the feed, gut microbes, and the host. Unfortunately, in aquaculture, the links between gut microbes and fish genetics and production phenotypes are not well understood.

In this study, we investigate the associations between gut microbial communities, fish feed conversion, and fish genetics in the domestic Atlantic salmon. Microbial community composition was determined for 230 juvenile fish from 23 full-sib families and was then regressed on growth, carbon and nitrogen metabolism, and feed efficiency. We only found weak associations between host genetics and microbial composition. However, we did identify significant (p < 0.05) associations between the abundance of three microbial operational taxonomical units (OTUs) and fish metabolism phenotypes. Two OTUs were associated with both carbon metabolism in adipose tissue and feed efficiency, while a third OTU was associated with weight gain.

In conclusion, this study demonstrates an intriguing association between host lipid metabolism and the gut microbiota composition in Atlantic salmon.
A firefly algorithm based hybrid method for structural topology optimization
Authors: Gebremedhen Hailu Shimels , Woldemichael Dereje Engida , Hashim Fakhruldin Mohd
Published: November 2020

In this paper, a firefly algorithm based hybrid algorithm through retaining global convergence of firefly algorithm and ability to generate connected topologies of optimality criteria (OC) method is proposed as an alternative method to solve stress-based topology optimization problems. The lower and upper limit of design variables (0 and 1) were used to find initial material distribution to initialize the firefly algorithm based section of the hybrid algorithm. Input parameters, the number of fireflies, and the number of function evaluations were determined before the implementation of the firefly algorithm to solve formulated problems. Since the direct application of the firefly algorithm cannot generate connected topologies, outputs from the firefly algorithm were used as an initial input material distribution for the OC method. The proposed method was validated using two-dimensional benchmark problems and the results were compared with results using the OC method. Weight percentage reduction, maximum stress-induced, optimal material distribution, and compliance were used to compare results. Results from the proposed method showed that the proposed method can generate connected topologies which are free from the interference of end-users, and only depend on boundary conditions or design variables. From the results, the objective function (weight of the design domain) can be further reduced in the range of 5 to 15% compared to the OC method.