bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of ESR1 (rs2234693 and rs9340799), CETP (rs708272), MTHFR (rs1801133 and rs2274976) and MS (rs185087) polymorphisms with Coronary Artery Disease (CAD)
Authors: Raina Jyotdeep Kour , Sharma Minakashee , Panjaliya Rakesh Kumar , Dogra Vikas , Bakaya Ashok , Kumar Parvinder
Published: July 2020

Background

Coronary artery disease (CAD) is a complex disease resulting from the cumulative and interactive effects of large number of genes along with environmental exposure. Therefore, the present study was envisaged as an effort to study the association of candidate genes ESR1 (rs2234693 and rs9340799), CETP (rs708272), MTHFR (rs1801133 and rs2274976) and MS (rs185087) polymorphisms with the risk of CAD, targeting the populations of Jammu (JandK).

Method

A total of 400 confirmed CAD patients and 400 healthy controls were enrolled for the present study. Genotyping was done by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP).

Results

ESR1 gene (rs9340799) polymorphism was found to be associated with CAD in all the genetic models. The haplotype analysis of ESR1 (rs2234693 and rs9340799) gene revealed that C-G haplotype was conferring approximately 5-fold risk and T-A haplotype was adding 1.4-fold risk towards the disease. ‘T’ allele of MTHFR rs1801133 SNP was observed to be responsible for development of CAD in our study population (p < 0.0001). In case of MTHFR (rs1801133 and rs2274976) gene, the haplotype T-G was observed to confer 4.7-fold risk towards CAD whereas haplotype C-G provided nearly a 1.7 fold protection towards development of CAD. For MS gene, rs185087 was also found to be associated with CAD in a co-dominant (p = 0.003 and p = 0.03), dominant (p = 0.001) and allelic models (p = 0.001). The gene-gene interaction revealed strong epistasis between single nucleotide polymorphisms (SNPs), ESR1 rs9340799 and MTHFR rs2274976. Furthermore, the dendrogram for gene-environment dataset indicated moderately synergistic interaction between CETP rs708272 and physical inactivity.

Conclusion

In the study under reference, a significant association of ESR1-XbaI (rs9340799), MTHFR C677T (rs1801133) and MS A2756G (rs185087) gene polymorphisms with the susceptibility of CAD in the population of Jammu region (JandK) has been observed.
Prognostic of different glomerular filtration rate formulas in patients receiving percutaneous coronary intervention: insights from a multicenter observational cohort
Authors: Chen Wei , Chen Pengyuan , Ni Zhonghan , Liu Yuanhui , Guo Wei , Jiang Lei , Wei Xuebiao , Chen Jiyan , Tan Ning , He Pengcheng , Guo Yansong
Published: July 2020

Background

The relationships of renal dysfunction (RD) and chronic kidney disease (CKD) with prognosis have been well established among non-ST elevation acute coronary syndrome (NSTE-ACS) patients who receive percutaneous coronary intervention (PCI), but the efficacy of different estimated glomerular filtration rate (eGFR) formulas for predicting the prognosis is unknown.

Methods

The cohort originated from a retrospective data, which consecutively enrolled 8197 patients. The eGFR was calculated by the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), CKD Epidemiology Collaboration-creatinine, CKD Epidemiology Collaboration-Cys-C, CKD Epidemiology Collaboration-Cys-C-creatinine and a modified abbreviated MDRD (c-aGFR) equations in Chinese CKD patients. Patients were excluded if the eGFR could not be obtained by one of the formulas. Patients were categorized as having normal renal function, mild RD, moderate RD, severe RD, or kidney failure to compare prognosis. The primary outcome was the in-hospital net adverse clinical events (NACE). The secondary outcomes were NACE and all-cause death during follow-up.

Results

In total, 2159 NSTE-ACS patients (age: 64.23 ± 10.25 years; males: 73.7%) were enrolled. 39 (1.8%) patients with in-hospital NACE were observed. During the 3.23 ± 1.55-year follow-up, 1.7% death and 4.2% NACE were observed in 1 year. The percentage of severe RD patients ranged from 15.4 to 39.2% according to different calculation formulas. A high prevalence of in-hospital NACE was observed in the severe RD groups (ranging from 8 to 14.3% for different formulas). Multiple regression analysis showed that a high eGFR is a protect factor against NACE and all-cause death regardless of the formula use. Receiver operating characteristic curves showed similar predictive performance of the c-aGFR when compared to other formulas (in-hospital NACE: AUC = 0.612, follow-up NACE: AUC = 0.622, and follow-up death: AUC = 0.711).

Conclusions

Severe RD results in a high prevalence of in-hospital NACE in NSTE-ACS patients after PCI regardless of the formulas use. Different formulas have a similar ability to predict in-hospital and long-term prognosis in NSTE-ACS patients. The c-aGFR formula is the simplest and a more convenient formula for use in practice.
Assessing human exposure to spotted fever and typhus group rickettsiae in Ontario, Canada (2013–2018): a retrospective, cross-sectional study
Authors: Nelder Mark P. , Russell Curtis B. , Johnson Steven , Li Ye , Cronin Kirby , Warshawsky Bryna , Brandon Nicholas , Patel Samir N.
Published: July 2020

Background

Assessing the burden of rickettsial infections in Ontario, Canada, is challenging since rickettsial infections are not reportable to public health. In the absence of reportable disease data, we assessed the burden of rickettsial infections by examining patient serological data and clinical information.

Methods

Our retrospective, cross-sectional study included patients who had Rickettsia serological testing ordered by their physician, in Ontario, from 2013 to 2018. We tested sera from 2755 non-travel patients for antibodies against spotted fever group rickettsiae (SFGR) and typhus group rickettsiae (TGR) using an indirect immunofluorescence assay (IFA) (positive IgG titers ≥1:64). We classified cases using a sensitive surveillance case definition: confirmed (4-fold increase in IgG titers between acute and convalescent sera with clinical evidence of infection), possible (single positive sera with clinical evidence) and previous rickettsial infection (single positive sera without clinical evidence). We classified cases seropositive for both SFGR and TGR as unspecified Rickettsia infections (URIs).

Results

Less than 5% of all patients had paired acute and convalescent sera tested, and of these, we found a single, laboratory-confirmed SFGR case, with a 4-fold increase in IgG titers and evidence of fever, maculopapular rash and headache. There were 45 possible (19 SFGR, 7 TGR, 19 URI) and 580 previous rickettsial infection (183 SFGR, 89 TGR, 308 URI) cases. The rate of positive tests for SFGR, TGR and URI combined (all case classifications) were 4.4 per 100,000 population. For confirmed and possible cases, the most common signs and symptoms were fever, headache, gastrointestinal complaints and maculopapular rash. The odds of having seropositive patients increased annually by 30% (odds ratio = 1.3, 95% confidence interval: 1.23–1.39).

Conclusions

The rates of rickettsial infections in Ontario are difficult to determine. Based on confirmed and possible cases, rates are low, but inclusion of previous rickettsial infection cases would indicate higher rates. We highlight the need for education regarding the importance of testing acute and convalescent sera and consistent completion of the laboratory requisition in confirming rickettsial disease. We suggest further research in Ontario to investigate rickettsial agents in potential vectors and clinical studies employing PCR testing of clinical samples.
Association of Single Measurement of dipstick proteinuria with physical performance of military males: the CHIEF study
Authors: Fan Chia-Hao , Lin Ssu-Chin , Tsai Kun-Zhe , Wu Tsung-Jui , Lin Yen-Po , Lin Yu-Kai , Lu Shao-Chi , Han Chih-Lu , Lin Gen-Min
Published: July 2020

Background

Proteinuria, a marker of kidney injury, may be related to skeletal muscle loss. Whether the severity of proteinuria is associated with physical performance is unclear.

Methods

We examined the association of proteinuria severity with physical performance cross-sectionally in 3357 military young males, free of chronic kidney disease, from the cardiorespiratory fitness and hospitalization events in armed Forces (CHIEF) study in Taiwan. The grades of proteinuria were classified according to one dipstick urinalysis which were collected at morning after an 8-h fast as unremarkable (0, +/−, and 1+), moderate (2+) and severe (3+ and 4+). Aerobic physical performance was evaluated by time for a 3000-m run and anaerobic physical performance was evaluated by numbers of 2-min sit-ups and 2-min push-ups, separately. Multiple linear regressions were used to determine the relationship.

Results

As compared with unremarkable proteinuria, moderate and severe proteinuria were dose-dependently correlated with 3000-m running time (β: 4.74 (95% confidence intervals (CI): − 0.55, 10.02) and 7.63 (95% CI: 3.21, 12.05), respectively), and inversely with numbers of 2-min push-ups (β = − 1.13 (− 1.97, − 0.29), and − 1.00 (− 1.71, − 0.28), respectively) with adjustments for age, service specialty, body mass index, blood pressure, alcohol intake, smoking, fasting plasma glucose, blood urea nitrogen, serum creatinine and physical activity. However, there was no association between proteinuria severity and 2-min sit-ups.

Conclusions

Our findings show a relationship of dipstick proteinuria with aerobic physical performance and parts of anaerobic physical performance in military healthy males. This mechanism is not fully understood and requires further investigations.
Bilateral carotid artery dissection due to Eagle syndrome in a patient with vascular Ehlers-Danlos syndrome: a case report
Authors: Ikenouchi Hajime , Takagi Masahito , Nishimura Ayako , Yamaguchi Eriko , Koge Junpei , Saito Kozue , Toyoda Kazunori , Koga Masatoshi
Published: July 2020

Background

Patients with vascular Ehlers-Danlos syndrome (EDS) occasionally suffer from arterial dissection. Eagle syndrome, which is caused by an elongated styloid process and also causes arterial dissection, is difficult to diagnose and could sometimes be overlooked. Little is known of the coexistence of these two diseases, and treatment strategy is not established. Here, we present a case of bilateral internal carotid artery (ICA) dissection due to Eagle syndrome in a patient with vascular EDS.

Case presentation

A 30-year-old man was admitted to our hospital because of sudden onset of mild sensory disturbance in his left limbs. He had a history of Ehlers-Danlos syndrome (EDS) and also had left cervical internal carotid artery (ICA) dissection 3 years before. Diffusion-weighted imaging showed acute cerebral infarcts in the right hemisphere. Cervical computed tomography angiography (CTA) revealed the right ICA narrowing at the cervical portion in addition to the previous left cervical ICA dissection. Cervical magnetic resonance imaging (MRI) revealed double-lumen and intramural hematoma at the narrowing portion of the right cervical ICA, which indicates arterial dissection. CT also revealed bilateral elongated styloid processes which are close to each side of cervical ICA. We diagnosed him as bilateral ICA dissection due to bilateral Eagle syndrome. Considering vascular complications due to vascular EDS, we performed closer follow-up with transoral carotid ultrasonography (TOCU). In 4 months, his right ICA dissection gradually improved without stroke recurrence or deterioration of dissection.

Conclusions

Since patients with vascular EDS easily develop arterial dissection, Eagle syndrome may be overlooked. Clinicians should consider Eagle syndrome in the case of vascular EDS with extracranial ICA dissection and close follow-up should be prioritized in cases of Eagle syndrome with vascular EDS.
Plasma glycated CD59 (gCD59), a novel biomarker for the diagnosis, management and follow up of women with Gestational Diabetes (GDM) – protocol for prospective cohort study
Authors: Bogdanet D. , O’Shea PM. , Halperin J. , Dunne F.
Published: July 2020

Background

The prevalence of Gestational Diabetes (GDM) is rising and with it the number of mothers and children at risk of adverse outcomes. As treatment has been shown to reduce adverse events, it is imperative that we identify all at-risk pregnant women. In Ireland, the national standard of care is selective screening with a 2-hour 75 g oral glucose tolerance test (OGTT). Aiming for universal screening is of utmost importance but this is difficult given the length, the unfeasibility and impracticability of the OGTT. We aim to assess if the novel biomarker glycated CD59 (gCD59) is a suitable contender for the OGTT in identifying women with GDM.

Methods

In this prospective cohort study, the study participants will be consecutive pregnant women at Galway University Hospital, Galway, Ireland. Samples for the plasma gCD59 biomarker will be taken together with routine bloods at the first antenatal visit, at weeks 24–28 at the time of routine 75 g OGTT, in trimester 3- and 12-weeks post-partum for women with GDM while having their routine post-partum 75 g OGTT. The constructed database will contain baseline information on each study participant, baseline laboratory data, follow-up laboratory data and pregnancy related outcomes. We aim to recruit a total of 2,000 participants over the project period and with a national GDM prevalence of 12–13%, we will have 240–260 subjects who meet OGTT criteria for GDM. Following regional prevalence, we expect to have 34–37 women who will develop either diabetes or pre-diabetes in the early post-partum period. The sensitivity and specificity of plasma gCD59 to predict the results of the OGTT will be assessed using nonparametric estimates of the receiver operating characteristic (ROC) curves and respective area under the ROC curve (AUROC).

Discussion

A body of clinical and experimental evidence supports a link between the complement system, complement regulatory proteins, and the pathogenesis of diabetes complications.

Building on this research, our study plans to look at the plasma gCD59 capacity to classify pregnant women with normal or abnormal glucose tolerance but also to assess if plasma gCD59 can be used as an early predictor for GDM, for adverse pregnancy outcomes and/or post-partum glucose intolerance.
Clinical characteristics and prognosis of anal squamous cell carcinoma: a retrospective audit of 144 patients from 11 cancer hospitals in southern China
Authors: Lu Yong , Wang Xiaohao , Li Peiyang , Zhang Tao , Zhou Jiaming , Ren Yufeng , Ding Yi , Peng Haihua , Wei Qichun , You Kaiyun , Ong Jason J. , Fairley Christopher K. , Grulich Andrew E. , Huang Meijin , Gao Yuanhong , Zou Huachun
Published: July 2020

Background

The incidence of anal squamous cell carcinoma (SCC) has been steadily growing globally in the past decade. Clinical data on anal SCC from China are rare. We conducted this study to describe the clinical and epidemiological characteristics of anal SCC in China and explore prognostic factors of outcomes among patients with anal SCC.

Methods

We audited demographic characteristics, relevant symptoms, risk factors, treatment modalities and outcomes for patients diagnosed with anal SCC at 11 medical institutions in China between January 2007 and July 2018.

Results

A total of 144 patients (109 females) were diagnosed with SCC during this period. Median age at initial diagnosis was 52.0 (interquartile range: 46.0–61.8) years. The most common symptoms were bleeding (n = 93, 64.6%), noticing a lump (n = 49, 34.0%), and pain (n = 47, 32.6%). The proportion of patients at the American Joint Committee on Cancer (AJCC) stages I-IV were 10 (6.9%), 22 (15.3%), 61 (42.4%) and 8 (5.6%), respectively, and AJCC stages in 43 (29.9%) patients were unknown. Thirty-six patients (25.0%) underwent abdominoperineal resection initially. Univariable analysis showed that T stage predicted recurrence-free survival (RFS) (Hazard ratio [HR] = 3.03, 95% Confidence interval [CI]: 1.10–8.37, p = 0.032), and age group (HR = 2.90, 95% CI: 1.12–7.49, p = 0.028), AJCC stage (HR = 4.56, 95% CI: 1.02–20.35, p = 0.046), and N stage (HR = 3.05, 95% CI: 1.07–8.74, p = 0.038) predicted overall survival (OS).

Conclusions

T stage was identified as prognostic factor of RFS, and age, AJCC stage, and N stage were identified as prognostic factors of OS. Improving symptom awareness and earlier presentation among patients potentially at risk for anal SCC should be encouraged. Familiarity with the standard treatment among health care providers in China should be further improved.
Assessment of retinal vascular oxygenation and morphology at stages of diabetic retinopathy in African Americans
Authors: Garvey Sarah L. , Khansari Maziyar M. , Jiang Xuejuan , Varma Rohit , Shahidi Mahnaz
Published: July 2020

Background

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of blindness in working-age adults. The likelihood of visual impairment associated with DR is two-fold higher in the African-American (AA) compared to non-Hispanic white. Although alterations in retinal vessel oxygenation and morphology have been reported in DR, there is limited knowledge about these vascular changes in AA subjects. The purpose of the current study was to investigate alterations in retinal vascular oxygen saturation (SO2), vessel diameter (D) and tortuosity at severity stages of DR in AA subjects.

Methods

A nested case-control study of 56 AA subjects was conducted. Right eyes were grouped as non-diabetic (ND) (N = 26), no clinical DR (NDR) (N = 19), or moderate/severe non-proliferative DR (NPDR) (N = 11). Imaging was performed using a commercially available scanning laser ophthalmoscope. Images were analyzed to determine retinal arterial and venous SO2 (SO2A and SO2V), diameter (DA and DV), and vessel tortuosity index (VTI) (VTIA and VTIV).

Results

SO2V and DV were higher in NPDR compared to ND and NDR groups (P < 0.05). There were no significant differences in SO2A and DA among ND, NDR, and NPDR groups (P > 0.8). Maximum VTIA was higher in diabetics (NDR and NPDR) compared to non-diabetics (P < 0.03). There was no significant difference in maximum VTIV among the 3 groups (P = 0.5).

Conclusions

The findings advance our understanding of DR pathophysiology in the AA population and may propel identification of race-specific retinal vascular biomarkers for improved diagnosis and monitoring of DR.
Sinhala translation of the Perinatal Anxiety Screening Scale: a valid and reliable tool to detect anxiety disorders among antenatal women
Authors: Priyadarshanie M. N. , Waas M. D. I. A. , Goonewardena C. S. E. , Balasuriya A. , Senaratna B. C. V. , Fernando D. M. S.
Published: July 2020

Background

Anxiety disorders during pregnancy are not routinely assessed in Sri Lanka despite being common and being associated with adverse pregnancy outcomes. Screening can facilitate early detection and management of anxiety and improve pregnancy outcomes. Our aim was to determine the validity of the Sinhala translation of the Perinatal Anxiety Screening Scale (PASS) to detect anxiety among Sri Lankan pregnant women.

Methods

A cross-sectional study was conducted in antenatal clinics of a teaching hospital in Colombo District. The PASS was translated to Sinhala using the standard translation/ back-translation method. Pregnant women (n = 221) were sequentially recruited and assessed by a psychiatrist until 81 women with anxiety disorder were diagnosed using the International Classification of Diseases-10 criteria (gold standard). The Sinhala translation of the PASS (PASS-S) was administered to all recruited women, including 140 women without anxiety. Receiver-Operating- Characteristic (ROC) analysis was performed, the optimal cut-off score for PASS-S was determined, and its validity was assessed using sensitivity, specificity, predictive values and positive and negative likelihood ratios. Internal consistency was assessed using Cronbach’s alpha. Test-retest and inter-rater reliability for PASS-S score and anxiety classification were assessed using intra class correlation coefficient (ICC) and Cohen’s kappa (k), respectively.

Results

The mean age (±SD) of women was 30(±5.8) years, and 53.7% were multiparous. A psychiatrist diagnosed anxiety disorder was made in 37.0% of women, while the PASS-S, at its optimal cut-off of ≥20, classified 37.5% of women as having anxiety disorders. The area under the ROC curve for the PASS-S was 0.96 (95%CI 0.94–0.99). Sensitivity, specificity and positive and negative predictive values of the PASS-S were 0.93 (95% CI 0.84–0.97), 0.90 (95% CI 0.83–0.94), 0.85 (95% CI 0.75–0.90) and 0.95 (95% CI 0.89–0.98), respectively. Positive and negative likelihood ratios were 8.8 (95% CI 5.3–14.5) and 0.08 (95%CI 0.04–0.18), respectively, and the internal consistency was high (Cronbach’s alpha 0.95). Four-factor structures obtained by exploratory factor analysis were “acute anxiety and adjustment”, “social anxiety, specific fears and trauma”, “perfectionism and control” and “general anxiety”.Test-retest reliability was high for the PASS-S score (ICC 0.85[95% CI 0.65–0.96]) and anxiety classification (k 0.77[95% CI 0.34–1.2]). Inter-interviewer reliability was also high (ICC 0.92[95% CI 0.81–0.97] for the PASS-S score and (k0.86 [95% CI 0.59–1.1] for anxiety classification).

Conclusion

The Sinhala translation of the PASS is a valid and reliable instrument to screen for anxiety disorders among antenatal women in Sri Lanka.
Child abuse in the West Bank of the occupied Palestinian territory (WB/oPt): social and political determinants
Authors: Harsha Nouh , Lynch Margaret A. , Giacaman Rita
Published: July 2020

Background

Child maltreatment is a global epidemic. It affects morbidity, mortality, social behavior, wellbeing, and quality of life of children. This study aims to assess prevalence of child abuse in the West Bank (WB) of the occupied Palestinian territory (oPt) and to determine some of its social and political associated factors.

Methods

We analyzed secondary data obtained from a cross sectional study conducted on a sample representing Palestinian children on the West Bank and using the International Society for the Prevention of Child Abuse and Neglect (ISPCAN) tool. The ISPCAN Child Abuse Screening Tool for parents (ICAST-P) questionnaire was completed by 1107 Palestinian mothers to estimate physical and emotional child abusive practices at home for children aged 0–12 years. Univariate, bivariate, and multivariate binary logistic regression analyses were performed using the SPSS® version 20 to assess prevalence and predictors of child abuse.

Results

Overall, around 34% of the West Bank-children were abused by their mothers. Results of the logistic regression analysis indicated that male children, children of younger mothers, children whose fathers were with low levels of education, children whose mothers reported low levels of parental warmth, and children whose parents were exposed to political violence were at greater risk of being abused.

Conclusions

Child abuse is highly prevalent among children of the Palestinian society in the West Bank. Policy makers need to pay more attention to this epidemic. The association between child abuse and political violence found in this study makes a just solution for Palestinians essential for improving the welfare of children and families.
The method for measurement of the three-dimensional scoliosis angle from standard radiographs
Authors: Główka Paweł , Politarczyk Wojciech , Janusz Piotr , Woźniak Łukasz , Kotwicki Tomasz
Published: July 2020

Background

Three-dimensional idiopathic scoliosis cannot be accurately assessed with the aid of a single plane parameter – the Cobb angle. We propose a novel method for evaluating the three-dimensional (3D) pattern of scoliosis based on two X-rays (PA and lateral). The proposed method consists of the measurements of the angles between the upper endplate of the upper-end vertebra and the lower endplate of the lower-end vertebra (3D scoliosis angle).

Methods

The 3D-angles of thirty scoliosis curves were measured with either computed tomography (CT) or digitally reconstructed radiographs (DRRs): PA and lateral. CT was used as a reference. In the case of CT, the 3D angle was calculated based on the coordinates of three points situated on the upper endplate and those of three points situated on the lower endplate of the scoliosis curve. In the case of the DRR, the 3D angle was calculated using the four-angle method: the angles formed by the endplates of the curve with the transverse plane. The results were tested with the Student’s t-test, and the agreement of measurements was tested with the intraclass correlation coefficient.

Results

There was no significant difference between the 3D-angle measurements obtained with DRRs versus CT, p > 0.05. There was, however, a significant difference between the 3D-scoliosis angle and the Cobb angle measurements performed based on the X-rays. The reproducibility and reliability of 3D angle measurements were high.

Conclusions

Based on two standard radiographs, PA and lateral, it is possible to calculate the 3D scoliosis angle. The proposed method facilitates 3D-scoliosis assessment without the use of sophisticated devices. Considering the 3D nature of AIS, the 3D parameters of the spine may help to apply a more effective treatment and estimate a more precise prognosis for patient with scoliosis.
Second opinions in medical oncology
Authors: Olver Ian , Carey Mariko , Bryant Jamie , Boyes Allison , Evans Tiffany , Sanson-Fisher Rob
Published: July 2020

Background

The current study aimed to further our understanding of second opinions among medical oncology patients by examining the proportion of patients who sought a second opinion about their cancer treatment, and why.

Methods

The study was conducted between 2013 and 2015 in three medical oncology clinics located in public hospitals in Australia: in metropolitan New South Wales, metropolitan Queensland, and in Tasmania.

Those patients who provide written informed consent were asked to complete a brief paper and pencil survey in the clinic containing questions on sociodemographic, disease and treatment characteristics. Approximately 1 month later, participants were mailed a second paper and pencil survey which contained questions about whether they had sought a second opinion and their motivation for doing so. Non-responders were followed up by letter at 3 and 6 weeks.

Results

Of 823 patients screened for eligibility, 698 eligible patients, 612 provided consent.

Of those who consented, 355 completed both the initial survey and the second survey and were included in the analyses. Of the 57 patients who sought a second opinion, the most frequent reasons given for doing so were the need for reassurance (49.1%) and the need to consider the range of treatment options (41.8%).

Of the 297 (83.6%) participants who did not seek a second opinion, the main reason was confidence in the first doctor (88.7%). Only 3.1% patients did not know that they could ask for a second opinion. Occasionally the doctor will initiate the referral for a second opinion.

Conclusions

Our study suggests that a minority of cancer patients seek a second opinion at some phase during their care. Most did so for reassurance or to ensure that they had covered all of the treatment options and not because of discomfort or distrust of their treating doctor.

Few patients reported a lack of awareness of second opinions. This suggests that second opinions form part of a patient-centred approach to information provision about care options. Whether the second opinion improves the quality of care or indeed outcomes has been difficult to demonstrate.
Defining rules governing recognition and Fc-mediated effector functions to the HIV-1 co-receptor binding site
Authors: Tolbert William D. , Sherburn Rebekah , Gohain Neelakshi , Ding Shilei , Flinko Robin , Orlandi Chiara , Ray Krishanu , Finzi Andrés , Lewis George K. , Pazgier Marzena
Published: July 2020

Background

The binding of HIV-1 Envelope glycoproteins (Env) to host receptor CD4 exposes vulnerable conserved epitopes within the co-receptor binding site (CoRBS) which are required for the engagement of either CCR5 or CXCR4 co-receptor to allow HIV-1 entry. Antibodies against this region have been implicated in the protection against HIV acquisition in non-human primate (NHP) challenge studies and found to act synergistically with antibodies of other specificities to deliver effective Fc-mediated effector function against HIV-1-infected cells. Here, we describe the structure and function of N12-i2, an antibody isolated from an HIV-1-infected individual, and show how the unique structural features of this antibody allow for its effective Env recognition and Fc-mediated effector function.

Results

N12-i2 binds within the CoRBS utilizing two adjacent sulfo-tyrosines (TYS) for binding, one of which binds to a previously unknown TYS binding pocket formed by gp120 residues of high sequence conservation among HIV-1 strains. Structural alignment with gp120 in complex with the co-receptor CCR5 indicates that the new pocket corresponds to TYS at position 15 of CCR5. In addition, structure-function analysis of N12-i2 and other CoRBS-specific antibodies indicates a link between modes of antibody binding within the CoRBS and Fc-mediated effector activities. The efficiency of antibody-dependent cellular cytotoxicity (ADCC) correlated with both the level of antibody binding and the mode of antibody attachment to the epitope region, specifically with the way the Fc region was oriented relative to the target cell surface. Antibodies with poor Fc access mediated the poorest ADCC whereas those with their Fc region readily accessible for interaction with effector cells mediated the most potent ADCC.

Conclusion

Our data identify a previously unknown binding site for TYS within the assembled CoRBS of the HIV-1 virus. In addition, our combined structural-modeling-functional analyses provide new insights into mechanisms of Fc-effector function of antibodies against HIV-1, in particular, how antibody binding to Env antigen affects the efficiency of ADCC response.
Blood transcriptomic discrimination of bacterial and viral infections in the emergency department: a multi-cohort observational validation study
Authors: Sampson Dayle , Yager Thomas D. , Fox Brian , Shallcross Laura , McHugh Leo , Seldon Therese , Rapisarda Antony , Hendriks Roslyn A. , Brandon Richard B. , Navalkar Krupa , Simpson Nandi , Stafford Sian , Gil Eliza , Venturini Cristina , Tsaliki Evi , Roe Jennifer , Chain Benjamin , Noursadeghi Mahdad
Published: July 2020

Background

There is an urgent need to develop biomarkers that stratify risk of bacterial infection in order to support antimicrobial stewardship in emergency hospital admissions.

Methods

We used computational machine learning to derive a rule-out blood transcriptomic signature of bacterial infection (SeptiCyte™ TRIAGE) from eight published case-control studies. We then validated this signature by itself in independent case-control data from more than 1500 samples in total, and in combination with our previously published signature for viral infections (SeptiCyte™ VIRUS) using pooled data from a further 1088 samples. Finally, we tested the performance of these signatures in a prospective observational cohort of emergency department (ED) patients with fever, and we used the combined SeptiCyte™ signature in a mixture modelling approach to estimate the prevalence of bacterial and viral infections in febrile ED patients without microbiological diagnoses.

Results

The combination of SeptiCyte™ TRIAGE with our published signature for viral infections (SeptiCyte™ VIRUS) discriminated bacterial and viral infections in febrile ED patients, with a receiver operating characteristic area under the curve of 0.95 (95% confidence interval 0.90–1), compared to 0.79 (0.68–0.91) for WCC and 0.73 (0.61–0.86) for CRP. At pre-test probabilities 0.35 and 0.72, the combined SeptiCyte™ score achieved a negative predictive value for bacterial infection of 0.97 (0.90–0.99) and 0.86 (0.64–0.96), compared to 0.90 (0.80–0.94) and 0.66 (0.48–0.79) for WCC and 0.88 (0.69–0.95) and 0.60 (0.31–0.72) for CRP. In a mixture modelling approach, the combined SeptiCyte™ score estimated that 24% of febrile ED cases receiving antibacterials without a microbiological diagnosis were due to viral infections. Our analysis also suggested that a proportion of patients with bacterial infection recovered without antibacterials.

Conclusions

Blood transcriptional biomarkers offer exciting opportunities to support precision antibacterial prescribing in ED and improve diagnostic classification of patients without microbiologically confirmed infections.
Optimized homomorphic encryption solution for secure genome-wide association studies
Authors: Blatt Marcelo , Gusev Alexander , Polyakov Yuriy , Rohloff Kurt , Vaikuntanathan Vinod
Published: July 2020

Background

Genome-Wide Association Studies (GWAS) refer to observational studies of a genome-wide set of genetic variants across many individuals to see if any genetic variants are associated with a certain trait. A typical GWAS analysis of a disease phenotype involves iterative logistic regression of a case/control phenotype on a single-neuclotide polymorphism (SNP) with quantitative covariates. GWAS have been a highly successful approach for identifying genetic-variant associations with many poorly-understood diseases. However, a major limitation of GWAS is the dependence on individual-level genotype/phenotype data and the corresponding privacy concerns.

Methods

We present a solution for secure GWAS using homomorphic encryption (HE) that keeps all individual data encrypted throughout the association study. Our solution is based on an optimized semi-parallel GWAS compute model, a new Residue-Number-System (RNS) variant of the Cheon-Kim-Kim-Song (CKKS) HE scheme, novel techniques to switch between data encodings, and more than a dozen crypto-engineering optimizations.

Results

Our prototype can perform the full GWAS computation for 1,000 individuals, 131,071 SNPs, and 3 covariates in about 10 minutes on a modern server computing node (with 28 cores). Our solution for a smaller dataset was awarded co-first place in iDASH’18 Track 2: “Secure Parallel Genome Wide Association Studies using HE”.

Conclusions

Many of the HE optimizations presented in our paper are general-purpose, and can be used in solving challenging problems with large datasets in other application domains.
Decentralized genomics audit logging via permissioned blockchain ledgering
Authors: Pattengale Nicholas D. , Hudson Corey M.
Published: July 2020

Background

One of the tasks in the iDASH Secure Genome Analysis Competition in 2018 was to develop blockchain-based immutable logging and querying for a cross-site genomic dataset access audit trail. The specific challenge was to design a time/space efficient structure and mechanism of storing/retrieving genomic data access logs, based on MultiChain version 1.0.4 (https://www.multichain.com/).

Methods

Our technique uses the MultiChain stream application programming interface (which affords treating MultiChain as a key value store) and employs a two-level index, which naturally supports efficient queries of the data for single clause constraints. The scheme also supports heuristic and binary search techniques for queries containing conjunctions of clause constraints, and timestamp range queries. Of note, all of our techniques have complexity independent of inserted data set size, other than the timestamp ranges, which logarithmically scale with input size.

Results

We implemented our insertion and querying techniques in Python, using the MultiChain library Savoir (https://github.com/dxmarkets/savoir), and comprehensively tested our implementation across a benchmark of datasets of varying sizes. We also tested a port of our challenge submission to a newer version of MultiChain (2.0 beta), which natively supports multiple indices.

Conclusions

We presented creative and efficient techniques for storing and querying log file data in MultiChain 1.0.4 and 2.0 beta. We demonstrated that it is feasible to use a permissioned blockchain ledger for genomic query log data when data volume is on the order of hundreds of megabytes and query times of dozens of minutes is acceptable. We demonstrated that evolution in the ledger platform (MultiChain 1 to 2) yielded a 30%-40% increase in insertion efficiency. All source code for this challenge has been made available under a BSD-3 license from https://github.com/sandialabs/idash2018task1/.
LPS aggravates lung inflammation induced by RSV by promoting the ERK-MMP-12 signaling pathway in mice
Authors: Chen Shenglin , Xie Jun , Zhao Keting , Ren Luo , Deng Yu , Xie Xiaohong , Chen Shiyi , Xu Hongmei , Long Xiaoru , Liu Enmei
Published: July 2020

Background

RSV can lead to persistent airway inflammation and airway hyperresponsiveness (AHR), and is intimately associated with childhood recurrent wheezing and asthma, but the underlying mechanisms remain unclear. Lipopolysaccharide (LPS) is also implicated in the onset and exacerbation of asthma. However, whether inhalation of LPS can boost airway inflammation induced by RSV is not clear. In this study, we utilized an LPS- and RSV-superinfected mouse model to explore underlying pathogenesis.

Methods

Mice were infected with RSV on day 0 and inoculated with LPS from day 35 to day 41, samples were collected on day 42. Inflammatory cells, lung histopathology and AHR were measured. Cytokines were detected by ELISA and ERK, JNK, p38 was determined by western blot. MMP408, PD98059, SP600125 and SB203580 were used to inhibit MMP-12, ERK, JNK and p38 respectively.

Results

LPS exposure superimposed on RSV-infected lungs could lead to more vigorous cellular influx, lung structures damage, augmented AHR and higher MMP-12 levels. Inhibition of MMP-12 or ERK signaling pathway in vivo both diminished LPS-driven airway inflammation and AHR.

Conclusions

Exposure to LPS in RSV-infected mice is associated with enhanced increases in ERK-MMP-12 expression that translates into increased lung inflammation and AHR. These findings contribute novel information to the field investigating the onset of post-RSV bronchiolitis recurrent wheezing as a result of LPS exposure.
A cultural and gender-based approach to understanding patient adjustment to chronic heart failure
Authors: Surikova Jelena , Payne Ada , Miller Karen-Lee , Ravaei Arian , Nolan Robert P.
Published: July 2020

Background

Persons identifying as Black, Chinese, or South Asian make up the largest minority groups in Canada. Individuals with chronic heart failure (CHF) from these groups experience a greater rate of re-hospitalization and poorer quality of life. Although experts agree that culture can shape the experience of CHF, little is known about how patients from these minority populations define a good quality of life with CHF and what barriers they experience when carrying out self-care behaviours. The aim of this qualitative study was to examine cultural and gender-based influences on quality of life in patients with CHF.

Methods

Purposive sampling included 30 patients (67% male), 18 to 75 years of age, who self-identified as Black (n = 8), Chinese (n = 9), or South Asian (n = 6). Caucasians (n = 7) were included as a comparison group. Semi-structured interviews (see the online appendix), lasting approximately 60 min, were conducted, which focused on personal understanding of CHF and living with the disease, including impact on lifestyle and quality of life. An inductive qualitative approach with thematic content analysis was used to develop key insights into individual experience of CHF, as well as cultural and gender-based influences on self-care and quality of life. Descriptive statistics were generated from questionnaire responses.

Results

Five key themes emerged from the narrative analysis of participant interviews: (i) CHF as an emergent reality, (ii) quality of life and disruption of lifecourse milestones, (iii) the challenge to accept CHF and re-evaluation of quality of life; (iv) impact on social activities essential to quality of life, and (v) life with CHF as a commitment to culturally tailored self-care. Participants described the unique impact of CHF on their quality of life, including life trajectory milestones such as dating, parenting, and retirement planning, as well as the importance of accepting their diagnosis, and the reframing goals for living well with heart failure. Positive and negative impacts on social relationships were noted, including sexual intimacy and interactions with spouses, other family members, and co-workers.

Conclusions

Study findings highlight important lifespan, cultural, and gender considerations that can inform the improvement of patient care and quality of life for patients and their families.
Patients’ confidence in treatment decisions for early stage non-small cell lung cancer (NSCLC)
Authors: Pompili Cecilia , Holch Patricia , Rogers Zoe , Absolom Kate , Clayton Beverly , Franks Kevin , Bekker Hilary , Velikova Galina
Published: July 2020

Background

In early-stage Non-Small Cell Lung Cancer (NSCLC) patients, little is known about how to measure patient participation in Shared-Decision Making (SDM). We examined the psychometric properties and clinical acceptability of the Decision Self-Efficacy scale (DSE) in a cohort of patients undergoing to Stereotactic Ablative Radiotherapy (SABR) or Video-assisted Thoracoscopic Surgery (VATS) to capture patient involvement in treatment decisions.

Methods

In the context of a prospective longitudinal study (Life after Lung Cancer-LiLAC) involving 244 patients with early-stage NSCLC, 158 (64.7%) patients completed the DSE either on paper or electronically online prior to treatment with SABR or VATS pulmonary resection. DSE psychometric properties were examined using: principal components analysis of item properties and internal structure, and internal construct validity; we also performed a sensitivity analysis according to Eastern Cooperative Oncology Group Performance Status (ECOG PS), gender, age and treatment received (VATS or SABR) difference.

Results

Exploratory factor analysis using polychoric correlations substantiated that the 11 item DSE is one scale accounting for 81% of the variance. We calculated a value of 0.96 for Cronbach’s alpha for the total DSE score.

DSE scores did not differ by gender (p = 0.37), between the two treatment groups (p = 0.09) and between younger and older patients (p = 0.4). However, patients with an ECOG PS > 1 have a DSE mean of 73.8 (SD 26) compared to patients with a PS 0–1 who have a DSE mean of 85.8 (SD 20.3 p = 0.002).

Conclusion

Findings provide preliminary evidence for the reliability and validity of the DSE questionnaire in this population. However, future studies are warranted to identify the most appropriate SDM tool for clinical practice in the lung cancer treatment field.
Stakeholders’ experiences of the public health research process: time to change the system?
Authors: Laird Yvonne , Manner Jillian , Baldwin Louise , Hunter Ruth , McAteer John , Rodgers Sarah , Williamson Chloë , Jepson Ruth
Published: July 2020

Background

The importance of engaging stakeholders in the research process is well recognised. Whilst engagement is important, guidelines and practices vary for how stakeholders should be involved in research and how to facilitate effective collaborative relationships.

Methods

This study aimed to explore the perspectives and experiences of stakeholders involved in the policy and practice area of outdoor space and non-communicable disease prevention. Stakeholders interviewed included academics, practitioners, policy-makers, knowledge brokers and a funder.

Results

The findings suggest that stakeholders had positive experiences when engaged meaningfully in the research process, where research projects were carefully planned and managed with attention to context and culture, and where the research team was effective, respectful and communicative. These factors help to facilitate the translation of research into policy and practice. However, multiple challenges of collaborative research were identified which related to structural and systemic challenges, building and maintaining relationships, use and collection of data and information, cultural perceptions of research and research generation, and getting evidence into action. Participants felt that changing the funding system, exploring more collaborative research methodologies, improved research translation, and more effective collaborative relationships at all stages of the research process could address some of these challenges.

Conclusions

The findings highlight that, whilst stakeholder engagement in research was considered important, structural, cultural and individual practices impacted how this worked in practice. Identifying and testing solutions to address these challenges could improve synergies between research, policy, and practice and lead to the production of impactful research that reduces wastage of public funding, improves implementation of findings and ultimately improves public health outcomes.
Comparison of different optomotor response readouts for visual testing in experimental autoimmune encephalomyelitis-optic neuritis
Authors: Hecker Christina , Dietrich Michael , Issberner Andrea , Hartung Hans-Peter , Albrecht Philipp
Published: July 2020

Optomotor response is increasingly used in preclinical research for evaluating the visual function in rodents. However, the most suitable measuring protocol for specific scientific questions is not always established. We aimed to determine the optimal parameters for visual function analysis in experimental autoimmune encephalomyelitis optic neuritis (EAEON), an animal model for multiple sclerosis. Contrast sensitivity as well as spatial frequency both had a low variance and a good test-retest reliability. Also, both parameters were able to differentiate between the EAEON and the control group. Correlations with the retinal degeneration, assessed by optical coherence tomography, the infiltration of immune cells, and the clinical disability score revealed that spatial frequency was superior to contrast sensitivity analysis. We therefore conclude that spatial frequency testing is better suited as visual acuity assessment in C57Bl/6 J EAEON mice. Furthermore, contrast sensitivity measurements are more time consuming, possibly leading to more stress for the animals.