bluuebunny/crossref_metadata_2025 huggingface dataset:
Sub-optimal gain in vision in retinal vein occlusion due to under-treatment in the real world: results from an open-label prospective study of Intravitreal Ranibizumab
Authors: Narayanan Raja , Kelkar Aditya , Abbas Zahir , Goel Neha , Soman Manoj , Naik Naveen , Sudhalkar Aditya , Walinjkar Jaydeep , Shah Utkarsh , Maksane Nitin
Published: January 2021

Background

Macular edema secondary to retinal vein occlusion (RVO) is an important cause of loss of vision. Intravitreal injections (IVI) of anti-vascular endothelial growth factor (VEGF) are the standard of care in this disease, as shown in numerous randomized controlled trials. The purpose of this study was to study the efficacy and safety of ranibizumab, an anti-VEGF agent, in the real-world setting.

Methods

This was 48 weeks, open-label, prospective, multicentre, observational study. Patients diagnosed with ME secondary to RVO were treated with IVI of Ranibizumab 0.5 mg in real-world conditions. Efficacy was measured by improvement seen in best-corrected visual acuity (BCVA) in terms of Early Treatment of Diabetic Retinopathy Study (ETDRS) Letter Scores and change in central retinal thickness (CRT) measured by optical coherence tomography.

Results

One hundred eyes of 100 patients (79 with branch retinal vein occlusion and 21 with central retinal vein occlusion) were recruited in the study. The mean (standard deviation, SD) BCVA was 52.8 (21.99) letters at baseline and 62.3 (24.40) letters at week 48. From baseline, there was a significant improvement in BCVA by 7.7 letters (p = 0.001) at 48 weeks. The mean (SD) of CRT was 479.9 (216.25) μm at baseline and it decreased significantly to 284.9 (171.35) μm at week 48 (p < 0.001). During the study period, the average number of intravitreal injections was 3.5 per patient. There was no report of endophthalmitis in any eye.

Conclusions

Ranibizumab is well tolerated and effective in treating macular edema secondary to RVO in real-world clinical settings. However, there is under-treatment compared to controlled clinical trials, and the gain in vision is sub-optimal with under-treatment.

Trial registration

Clinical Trials Registry - India: CTRI/2015/07/005985.
A comparison of optic disc area measured by confocal scanning laser tomography versus Bruch’s membrane opening area measured using optical coherence tomography
Authors: Cazana Ioana Maria , Böhringer Daniel , Reinhard Thomas , Evers Charlotte , Engesser Diana , Anton Alexandra , Lübke Jan
Published: January 2021

Background

Precise optic disc size measurements based on anatomically exact disc margins are fundamental for a correct assessment of glaucoma suspects. Computerized imaging techniques, such as confocal-scanning-laser-tomography (CSLT), which applies operator defined boundaries and optical-coherence-tomography (OCT), which incorporates an alternative detectable landmark (Bruch’s-membrane-opening (BMO)), have simplified the planimetry of the optic disc and BMO-area, respectively. This study’s objectives are to compare both modalities for area and to define a threshold for macro-BMO using BMO-OCT.

Methods

Retrospectively, patients that simultaneously received CSLT and BMO-OCT scans were included. Their images were correlated and agreement was determined using Bland-Altman-analysis. The diagnostic power of a macro-BMO threshold using OCT was derived after creating a receiver-operating-characteristics-curve using the well-established analogous CSLT threshold (2.43 mm2).

Results

Our study included 373 eyes with a median optic disc area by CSLT/ BMO-area by OCT of 2.56 mm2 and 2.19 mm2 respectively. The Bland-Altman-analysis revealed a systematic deviation with a diverging tendency with increasing area, which enabled the creation of the following mathematical relation: disc-area (CSLT)*0.73 + 0.3 = BMO-area (OCT). BMO-area of 2.19 mm2 showed the best diagnostic power for identifying macro-BMOs using OCT (sensitivity: 75%, specificity: 86%).

Conclusions

Area measurements (CSLT optic disc area vs. BMO-area by OCT) showed a systematic deviation with a divergent tendency with increasing size. Our mathematical equation offers an estimated comparison of these anatomically diverse entities. Considering BMO-OCT´ anatomical accuracy, the 2.19 mm2 threshold may improve discernment between glaucoma suspects and norm variants.
Correlates of uptake of HIV testing among children and young adolescents in Akwa-Ibom state, Nigeria: a secondary data analysis of the Akwa-Ibom aids indicator survey, 2017
Authors: Adetoro Damilola , Khamofu Hadiza , Badru Titilope , Markson John , Adedokun Oluwasanmi , Sandah-Abubakar Nana , Dafa Ibrahim , Chen Mario , Chiegil Robert , Torpey Kwasi
Published: January 2021

Background

In order to end the AIDS epidemic by 2030, there is a need to significantly reduce the rate of new infection among children and young adolescents. Identifying the correlates of testing behaviour is necessary to improve HIV testing campaigns by refining messages that target individuals in this age group. The objective of this study was to determine the correlates of HIV testing among children and young adolescents in Akwa-Ibom, Nigeria.

Methods

The outcome was a secondary data analysis of the 2017 Akwa-Ibom AIDS Indicator Survey. Data of 4037 children and young adolescents aged 0–14 years was assessed in this study. Analysis was done using STATA version 16. Chi-squared test and logistic regression models were used to measure association and its strength between uptake of HIV testing and some independent variables (child/caregiver’s age, sex, educational status, child’s location, caregiver’s knowledge of HIV and caregiver ever tested for HIV) at 5% significance level.

Results

Result showed that only 14.2% of the children and young adolescents have been tested for HIV. Previous history of blood transfusion (AOR = 5.33, 95%C.I = 2.60–10.92, P = < 0.001), caregiver’s level of education (AOR = 2.67, 95%C.I = 1.30–5.51, P = 0.008) and caregiver ever tested for HIV (AOR = 8.31, 95%C.I = 5.67–12.19, P = < 0.001) were significantly associated with uptake of HIV testing.

Conclusion

This study concludes that a large proportion of children and young adolescents in Akwa-Ibom state have never been tested for HIV. There is a need for HIV testing interventions to be targeted towards this age groups and their parents/guardian. Addressing the knowledge gap amongst caregivers especially in rural areas is crucial towards improving the effectiveness of HIV testing interventions.
Serum lithium test requesting across three UK regions: an evaluation of adherence to monitoring guidelines
Authors: Parfitt Ceri , Duff Christopher J. , Scargill Jonathan , Green Lewis , Holland David , Heald Adrian H. , Fryer Anthony A.
Published: January 2021

Background

Bipolar disorder is the fourth most common mental health condition, affecting ~ 1% of UK adults. Lithium is an effective treatment for prevention of relapse and hospital admission, and is widely recommended as a first-line treatment. We previously showed in other areas that laboratory testing patterns are variable with sub-optimal conformity to guidance. We therefore examined lithium results and requesting patterns relative to monitoring recommendations.

Methods

Data on serum lithium levels and intervals between requests were extracted from Clinical Biochemistry laboratory information systems at the University Hospitals of North Midlands, Salford Royal Foundation Trust and Pennine Acute Hospitals from 2012 to 2018 (46,555 requests; 3371 individuals). Data were examined with respect to region/source of request, age and sex.

Results

Across all sites, lithium levels on many requests were outside the recommended UK therapeutic range (0.4–0.99 mmol/L); 19.2% below the range and 6.1% above the range (median [Li]: 0.60 mmol/L). A small percentage were found at the extremes (3.2% at < 0.1 mmol/L, 1.0% at ≥1.4 mmol/L). Most requests were from general practice (56.3%) or mental health units (34.4%), though those in the toxic range (≥1.4 mmol/L) were more likely to be from secondary care (63.9%). For requesting intervals, there was a distinct peak at 12 weeks, consistent with guidance for those stabilised on lithium therapy. There was no peak at 6 months, as recommended for those aged < 65 years on unchanging therapy, though re-test intervals in this age group were more likely to be longer. There was a peak at 0–7 days, reflecting those requiring closer monitoring (e.g. treatment initiation, toxicity). However, for those with initial lithium concentrations within the BNF range (0.4–0.99 mmol/L), 69.4% of tests were requested outside expected testing frequencies.

Conclusions

Our data showed: (a) lithium levels are often maintained at the lower end of the recommended therapeutic range, (b) patterns of lithium results and testing frequency were comparable across three UK sites with differing models of care and, (c) re-test intervals demonstrate a noticeable peak at the recommended 3-monthly, but not at 6-monthly intervals. Many tests were repeated outside expected frequencies, indicating the need for measures to minimise inappropriate testing.
A digital lifestyle behaviour change intervention for the prevention of type 2 diabetes: a qualitative study exploring intuitive engagement with real-time glucose and physical activity feedback
Authors: Whelan Maxine E. , Denton Francesca , Bourne Claire L. A. , Kingsnorth Andrew P. , Sherar Lauren B. , Orme Mark W. , Esliger Dale W.
Published: January 2021

Background

Mobile health technologies have advanced to now allow monitoring of the acute physiological responses to lifestyle behaviours. Our aim was to explore how people engaged with real-time feedback on their physical activity and glucose levels over several weeks.

Methods

Semi-structured interviews with 26 participants (61.5% female, 56.6 years) at moderate-to-high risk of developing type 2 diabetes were conducted. Interviews were completed after participants took part in an intervention comprising a flash glucose monitor (Freestyle Libre) and a physical activity monitor (Fitbit Charge 2). Purposive sampling ensured representation of ages, genders and group allocations.

Results

Inductive thematic analysis revealed how individuals intuitively used, interpreted and acted on feedback from wearable technologies. Six key themes emerged: triggers of engagement with the technologies, links between behaviour and health, lack of confidence, changes to movement behaviours, changes to diet and barriers to lifestyle behaviour change.

Conclusions

Our findings demonstrate that accessing behavioural and physiological feedback can increase self-awareness of how lifestyle impacts short-term health. Some participants noticed a link between the feedback presented by the two devices and changed their behaviour but many did not. Training and educational support, as well as efforts to optimize how feedback is presented to users, are needed to sustain engagement and behaviour change. Extensions of this work to involve people with diabetes are also warranted to explore whether behavioural and physiological feedback in parallel can encourage better diabetes self-management.

Trial registration

ISRCTN Registry, ISRCTN17545949, 12/05/2017, prospectively registered.
Simulating preventative testing of SARS-CoV-2 in schools: policy implications
Authors: Asgary Ali , Cojocaru Monica Gabriela , Najafabadi Mahdi M. , Wu Jianhong
Published: January 2021

Background

School testing for SARS-CoV-2 infection has become an important policy and planning issue as schools were reopened after the summer season and as the COVID-19 pandemic continues. Decisions to test or not to test and, if testing, how many tests, how often and for how long, are complex decisions that need to be taken under uncertainty and conflicting pressures from various stakeholders.

Method

We have developed an agent-based model and simulation tool that can be used to analyze the outcomes and effectiveness of different testing strategies and scenarios in schools with various number of classrooms and class sizes. We have applied a modified version of a standard SEIR disease transmission model that includes symptomatic and asymptomatic infectious populations, and that incorporates feasible public health measures. We also incorporated a pre-symptomatic phase for symptomatic cases. Every day, a random number of students in each class are tested. If they tested positive, they are placed in self-isolation at home when the test results are provided. Last but not least, we have included options to allow for full testing or complete self-isolation of a classroom with a positive case.

Results

We present sample simulation results for parameter values based on schools and disease related information, in the Province of Ontario, Canada. The findings show that testing can be an effective method in controlling the SARS-CoV-2 infection in schools if taken frequently, with expedited test results and self-isolation of infected students at home.

Conclusions

Our findings show that while testing cannot eliminate the risk and has its own challenges, it can significantly control outbreaks when combined with other measures, such as masks and other protective measures.
Pulmonary cavitation: an under-recognized late complication of severe COVID-19 lung disease
Authors: Zoumot Zaid , Bonilla Maria-Fernanda , Wahla Ali S. , Shafiq Irfan , Uzbeck Mateen , El-Lababidi Rania M. , Hamed Fadi , Abuzakouk Mohamed , ElKaissi Mahmoud
Published: January 2021

Background

Pulmonary radiological findings of the novel coronavirus disease 2019 (COVID-19) have been well documented and range from scattered ground-glass infiltrates in milder cases to confluent ground-glass change, dense consolidation, and crazy paving in the critically ill. However, lung cavitation has not been commonly described in these patients. The objective of this study was to assess the incidence of pulmonary cavitation in patients with COVID-19 and describe its characteristics and evolution.

Methods

We conducted a retrospective review of all patients admitted to our institution with COVID-19 and reviewed electronic medical records and imaging to identify patients who developed pulmonary cavitation.

Results

Twelve out of 689 (1.7%) patients admitted to our institution with COVID-19 developed pulmonary cavitation, comprising 3.3% (n = 12/359) of patients who developed COVID-19 pneumonia, and 11% (n = 12/110) of those admitted to the intensive care unit. We describe the imaging characteristics of the cavitation and present the clinical, pharmacological, laboratory, and microbiological parameters for these patients. In this cohort six patients have died, and six discharged home.

Conclusion

Cavitary lung disease in patients with severe COVID-19 disease is not uncommon, and is associated with a high level of morbidity and mortality.
Cardiorespiratory coupling is associated with exercise capacity in patients with chronic obstructive pulmonary disease
Authors: Huang Yu-Chen , Lin Ting-Yu , Wu Hau-Tieng , Chang Po-Jui , Lo Chun-Yu , Wang Tsai-Yu , Kuo Chih-Hsi Scott , Lin Shu-Min , Chung Fu-Tsai , Lin Horng-Chyuan , Hsieh Meng-Heng , Lo Yu-Lun
Published: January 2021

Background

The interaction between the pulmonary function and cardiovascular mechanics is a crucial issue, particularly when treating patients with chronic obstructive pulmonary disease (COPD). Synchrogram index is a new parameter that can quantify this interaction and has the potential to apply in COPD patients. Our objective in this study was to characterize cardiorespiratory interactions in terms of cardiorespiratory coupling (CRC) using the synchrogram index of the heart rate and respiratory flow signals in patients with chronic obstructive pulmonary disease.

Methods

This is a cross-sectional and preliminary data from a prospective study, which examines 55 COPD patients. K-means clustering analysis was applied to cluster COPD patients based on the synchrogram index. Linear regression and multivariable regression analysis were used to determine the correlation between the synchrogram index and the exercise capacity assessed by a six-minute walking test (6MWT).

Results

The 55 COPD patients were separated into a synchronized group (median 0.89 (0.64–0.97), n = 43) and a desynchronized group (median 0.23 (0.02–0.51), n = 12) based on K-means clustering analysis. Synchrogram index was correlated significantly with six minutes walking distance (r = 0.42, p = 0.001) and distance saturation product (r = 0.41, p = 0.001) assessed by 6MWT, and still was an independent variable by multivariable regression analysis.

Conclusion

This is the first result studying the heart–lung interaction in terms of cardiorespiratory coupling in COPD patients by the synchrogram index, and COPD patients are clustered into synchronized and desynchronized groups. Cardiorespiratory coupling is associated with exercise capacity in patients with COPD.
Prone during pandemic: development and implementation of a quality-based protocol for proning severe COVID-19 hypoxic lung failure patients in situationally or historically low resource hospitals
Authors: Astua Alfredo J. , Michaels Eli K. , Michaels Andrew J.
Published: January 2021

Background

Intermittent Prone Positioning (IPP) for Acute Respiratory Distress Syndrome (ARDS) decreases mortality. We present a program for IPP using expedient materials for settings of significant limitations in both overwhelmed established ICUs and particularly in low- and middle-income countries (LMICs) treating ARDS due to COVID-19 caused by SARS CoV-2.

Methods

The proning program evolved based on the principles of High Reliability Organizations (HROs) and Crew Resource Management (CRM). Patients with severe ARDS [PaO2:FiO2 ratio (PFr) ≤ 150 on FiO2 ≥ 0.6 and PEEP ≥ 5 cm H2O] received IPP. Patients were placed prone 16 h each day. When PFr was ≥ 200 for > 8 h supine IPP ceased. IPP used available materials without requiring additional work from the bedside team. Changes in PFr, PaCO2, and the SaO2:FiO2 ratio (SaFr) positionally were evaluated using t-statistics and ANOVA with Bonferroni correction (p < 0.017).

Results

Between 14APR2020 and 09MAY2020, at the peak of deaths in New York, there were 202 IPPs in 29 patients. Patients were 58.5 ± 1.7 years of age (37, 73), 76% male and had a body mass index (BMI) of 27.8 ± 0.8 (21, 38). Pressor agents were used in 76% and 17% received dialysis. The PFr prior to IPP was 107.5 ± 5.6 and 1 h after IPP was 155.7 ± 11.2 (p < 0.001 compared to pre-prone). PFr after the patients were placed supine was 131.5 ± 9.1 (p = 0.02). Pre-prone PaCO2 was 60.0 ± 2.5 and the 1-h post-prone PaCO2 was 67.2 ± 3.1 (p = 0.02). Supine PaCO2 after IPP was 60.4 ± 3.4 (p = 0.90). The SaFr prior to IPP was 121.3 ± 4.2 and the SaFr 1 h after positioning was 131.5 ± 5.1 (p = 0.03). The post-IPP supine SaFr was 139.7 ± 5.9 (p < 0.001). With ANOVA and Bonferroni correction there were statistically significant changes in PFr (p < 0.001) and SaFr (p < 0.001) and no significant changes in PaCO2 over the four time points measured. Using regression coefficients, the SaFrs predicted by PFrs of 150 and 200 at baseline are 133.2 and 147.3, respectively.

Conclusions

An IPP program for patients with COVID-19 ARDS can be instituted rapidly, safely, and effectively during an overwhelming mass casualty scenario. This approach may be equally applicable in both traditionally austere environments in LMICs and in otherwise capable centers facing situational resource limitations.
Neglect of relevant treatment recommendations in the conduct and reporting of a laser therapy knee osteoarthritis trial: letter to the editor
Authors: Stausholm Martin Bjørn , Bjordal Jan Magnus
Published: January 2021

We read with interest the article by Gomes et al. entitled: “Exercise program combined with electrophysical modalities in subjects with knee osteoarthritis: A randomised, placebo-controlled clinical trial”. Gomes et al. concluded that the low-level laser therapy (LLLT) did not reduce knee osteoarthritis pain when applied as an adjunct to exercise therapy. We argue that Gomes et al. neglected relevant laser treatment recommendations in the conduct and reporting of the trial.

Gomes et al. did not state the Joules per treatment spot applied. We calculated the Joules applied from other laser information in the report and found that it is too low of a dose according to the World Association for Laser Therapy (WALT) guidelines. Furthermore, we have published a meta-analysis of 22 placebo-controlled trials demonstrating a significant difference in pain-relieving effect between doses in adherence and non-adherence to the WALT guidelines. However, neither the WALT guidelines, nor our meta-analysis was mentioned by Gomes et al.

Moreover, Gomes et al. did not state whether the output power of the laser device was measured, and this is concerning because in the city of São Paulo, where the trial was conducted, most laser devices have been found to deliver less of a dose than specified by the manufacturers.

In summary, we found that the best available evidence regarding effective and ineffective LLLT dosing from systematic reviews was neglected in the conduct and reporting of the trial, and that the laser device may not have been calibrated.
The predictive factors that are associated with the number of sutures used during meniscal repair
Authors: Song Xiaoxiao , Chen Dongyang , Qi Xinsheng , Jiang Qing , Xia Caiwei
Published: January 2021

Purpose

To investigate factors associated with the consumption of a large number of sutures during arthroscopic meniscus repair procedures.

Methods

All patients who received meniscal repair, with or without concomitant anterior cruciate ligament (ACL) reconstruction, in our hospital from January 2015 to December 2019 were included in the current study. Demographic data (sex, age, body mass index (BMI), and injury-to-surgery interval) and surgical data (the site of the tear, side of the meniscus, presence of an ACL rupture or not and the number of sutures) were retrospectively collected from our medical records. The number of sutures was divided into two groups (1–2 sutures versus > 2 sutures). The stitching process was implemented through an all-inside technique using a meniscal repair device (Fast-Fix; Smith & Nephew). According to the length and stability of the meniscal tear, one to seven sutures were used. Univariate analysis consisted of chi-square tests. Multivariate logistic regression was then performed to adjust for confounding factors.

Results

A total of 242 patients, including 168 males and 57 females, was finally included. In the univariate analysis, we found that those patients who underwent meniscus repair within one month after meniscus tear were more likely to need fewer sutures than those who underwent surgery more than one month after injury (70/110 versus 59/115, p=0.062). In total, 75/109 (68.8%) lateral meniscal tears were repaired with fewer sutures than medial (34/72, 47.2%) and bilateral meniscus injuries (20/44, 45.4%; p=0.003). In the multivariate analysis, we found that the duration of injury (OR, 2.06; 95% CI, 1.16–3.64, p=0.013), presence of an ACL injury (OR, 3.76; 95% CI, 1.97–7.21, p< 0.001) and the side of the meniscus (OR, 0.31; 95% CI, 0.14–0.65, p=0.002) were associated with the number of sutures used during meniscal repair procedures.

Conclusions

Patients who underwent meniscal repair within one month after meniscus tear, especially lateral menisci tears, were more likely to need fewer sutures.

Study design

Case-control study; level of evidence, 3.
Skin autofluorescence predicts new cardiovascular disease and mortality in people with type 2 diabetes
Authors: Boersma Henderikus E. , van Waateringe Robert P. , van der Klauw Melanie M. , Graaff Reindert , Paterson Andrew D. , Smit Andries J. , Wolffenbuttel Bruce H. R.
Published: January 2021

Background

Skin autofluorescence (SAF) is a non-invasive marker of tissue accumulation of advanced glycation endproducts (AGE). Recently, we demonstrated in the general population that elevated SAF levels predict the development of type 2 diabetes (T2D), cardiovascular disease (CVD) and mortality. We evaluated whether elevated SAF may predict the development of CVD and mortality in individuals with T2D.

Methods

We included 2349 people with T2D, available baseline SAF measurements (measured with the AGE reader) and follow-up data from the Lifelines Cohort Study. Of them, 2071 had no clinical CVD at baseline. 60% were already diagnosed with diabetes (median duration 5, IQR 2–9 years), while 40% were detected during the baseline examination by elevated fasting blood glucose ≥7.0 mmol/l) and/or HbA1c ≥6.5% (48 mmol/mol).

Results

Mean (±SD) age was 57 ± 12 yrs., BMI 30.2 ± 5.4 kg/m2. 11% of participants with known T2D were treated with diet, the others used oral glucose-lowering medication, with or without insulin; 6% was using insulin alone. Participants with known T2D had higher SAF than those with newly-detected T2D (SAF Z-score 0.56 ± 0.99 vs 0.34 ± 0.89 AU, p < 0.001), which reflects a longer duration of hyperglycaemia in the former group. Participants with existing CVD and T2D had the highest SAF Z-score: 0.78 ± 1.25 AU. During a median follow-up of 3.7 yrs., 195 (7.6%) developed an atherosclerotic CVD event, while 137 (5.4%) died. SAF was strongly associated with the combined outcome of a new CVD event or mortality (OR 2.59, 95% CI 2.10–3.20, p < 0.001), as well as incidence of CVD (OR 2.05, 95% CI 1.61–2.61, p < 0.001) and death (OR 2.98, 2.25–3.94, p < 0.001) as a single outcome. In multivariable analysis for the combined endpoint, SAF retained its significance when sex, systolic blood pressure, HbA1c, total cholesterol, eGFR, as well as antihypertensive and statin medication were included. In a similar multivariable model, SAF was independently associated with mortality as a single outcome, but not with incident CVD.

Conclusions

Measuring SAF can assist in prediction of incident cardiovascular disease and mortality in individuals with T2D. SAF showed a stronger association with future CVD events and mortality than cholesterol or blood pressure levels.
Addressing unmet basic needs for children with sickle cell disease in the United States: clinic and staff perspectives
Authors: Loo Stephanie , Brochier Annelise , Wexler Mikayla Gordon , Long Kristin , Kavanagh Patricia L. , Garg Arvin , Drainoni Mari-Lynn
Published: January 2021

Background

The purpose of this study was to assess pediatric hematology clinic staff’s perspectives regarding barriers and facilitators in addressing unmet basic needs for children with sickle cell disease (SCD).

Methodology

Six focus groups were held at four urban pediatric hematology clinics in the Northeastern region of the United States from November to December 2019. Discussion questions were developed to align with the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) implementation science framework, focusing on the domains of context and recipient and how clinics address adverse social determinants of health (SDoH) in their patient populations. A summative content analytical approach was taken to identify major themes in the data.

Results

We discerned the following themes: (1) families of children with SCD experience numerous unmet basic needs; (2) clinic staff believed they had a role to play in addressing these unmet basic needs; (3) staff felt their ability to address families’ unmet basic needs depended upon caregivers’ capacity to act on staff’s recommendations; and (4) clinic staff’s ability to address these needs was limited by organizational and systemic factors beyond their control.

Conclusions

These findings have important implications for how best to address adverse SDoH for this vulnerable pediatric population so that urban-based pediatric hematology clinics can more equitably support families.
Prognostic values, ceRNA network, and immune regulation function of SDPR in KRAS-mutant lung cancer
Authors: Luo Xiaoqing , Peng Shunli , Ding Sijie , Zeng Qin , Wang Rong , Ma Yueyun , Chen ShiYu , Wang Yanxia , Wang Wei
Published: January 2021

Background

Serum Deprivation Protein Response (SDPR) plays an important role in formation of pulmonary alveoli. However, the functions and values of SDPR in lung cancer remain unknown. We explored prognostic value, expression pattern, and biological function of SDPR in non-small cell lung cancer (NSCLC) and KRAS-mutant lung cancers.

Methods

SDPR expression was evaluated by quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and Western blot on human NSCLC cells, lung adenocarcinoma tissue array, KRAS-mutant transgenic mice, TCGA and GEO datasets. Prognostic values of SDPR were evaluated by Kaplan–Meier and Cox regression analysis. Bioinformatics implications of SDPR including SDPR-combined transcription factors (TFs) and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules, and tumor infiltration models were illustrated.

Results

SDPR expression was downregulated in tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients both in lung cancer and KRAS-mutant subgroups. Meanwhile, ceRNA network was constructed to clarify the regulatory and biological functions of SDPR. Negative correlations were found between SDPR and immune checkpoint molecules (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns.

Conclusions

This study elucidated regulation network of SDPR in KRAS-mutant NSCLC, and it illustrated correlations between low SDPR expression and suppressed immune system, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC.
Exosome-based detection of EGFR T790M in plasma and pleural fluid of prospectively enrolled non-small cell lung cancer patients after first-line tyrosine kinase inhibitor therapy
Authors: Kim Yoonjung , Shin Saeam , Lee Kyung-A
Published: January 2021

Background

The exosomal nucleic acid (exoNA) from the plasma and pleural fluid can potentially provide means to identify genomic changes in non-small cell lung cancer (NSCLC) patients who develop resistance to targeted epidermal growth factor receptor (EGFR) inhibitor therapy.

Methods

We compared the performance of the following tools to detect EGFR mutations in 54 plasma samples and 13 pleural fluid using cfDNA, combined TNA (exoTNA + cfTNA), or total cellular DNA: droplet digital PCR (ddPCR), the Cobas® EGFR Mutation Test v2 (Cobas) and NGS with Oncomine Pan-Cancer Cell-Free Assay.

Results

All three of these platforms demonstrated 100% specificity in the detection of EGFR mutations in the plasma. In the detection of an activating mutation (exon 19 deletion and L858R), Cobas using cfDNA, ddPCR using combined TNA, and NGS using combined TNA showed a sensitivity of 93, 95.3, and 93.8%, respectively. For T790M mutation detection, the Cobas, ddPCR, and NGS showed a sensitivity of 64.7, 88.2, and 93.3%, respectively. Pleural fluid analysis revealed enrichment of the T790M mutant copies in the exosomes. ddPCR using exoTNA showed higher sensitivity than did total cellular DNA from the pleural fluid.

Conclusion

These results demonstrated that combined TNA in the plasma and exoTNA in the pleural fluid can be used to evaluate low-abundant EGFR mutant copies in NSCLC.
Comparisons of simulation results between passive and active fluid structure interaction models for left ventricle in hypertrophic obstructive cardiomyopathy
Authors: Huang Xueying , Deng Long , Zuo Heng , Yang Chun , Song Yunhu , Lesperance Mary , Tang Dalin
Published: January 2021

Background

Patient-specific active fluid–structure interactions (FSI) model is a useful approach to non-invasively investigate the hemodynamics in the heart. However, it takes a lot of effort to obtain the proper external force boundary conditions for active models, which heavily restrained the time-sensitive clinical applications of active computational models.

Methods

The simulation results of 12 passive FSI models based on 6 patients’ pre-operative and post-operative CT images were compared with corresponding active models to investigate the differences in hemodynamics and cardiac mechanics between these models.

Results

In comparing the passive and active models, it was found that there was no significant difference in pressure difference and shear stress on mitral valve leaflet (MVL) at the pre-SAM time point, but a significant difference was found in wall stress on the inner boundary of left ventricle (endocardium). It was also found that pressure difference on the coapted MVL and the shear stress on MVL were significantly decreased after successful surgery in both active and passive models.

Conclusion

Our results suggested that the passive models may provide good approximated hemodynamic results at 5% RR interval, which is crucial for analyzing the initiation of systolic anterior motion (SAM). Comparing to active models, the passive models decrease the complexity of the modeling construction and the difficulty of convergence significantly. These findings suggest that, with proper boundary conditions and sufficient clinical data, the passive computational model may be a good substitution model for the active model to perform hemodynamic analysis of the initiation of SAM.
Inferential challenges when assessing racial/ethnic health disparities in environmental research
Authors: Benmarhnia Tarik , Hajat Anjum , Kaufman Jay S.
Published: January 2021

Numerous epidemiologic studies have documented environmental health disparities according to race/ethnicity (R/E) to inform targeted interventions aimed at reducing these disparities. Yet, the use of R/E under the potential outcomes framework implies numerous underlying assumptions for epidemiologic studies that are often not carefully considered in environmental health research. In this commentary, we describe the current state of thinking about the interpretation of R/E variables in etiologic studies. We then discuss how such variables are commonly used in environmental epidemiology. We observed three main uses for R/E: i) as a confounder, ii) as an effect measure modifier and iii) as the main exposure of interest either through descriptive analysis or under a causal framework. We identified some common methodological concerns in each case and provided some practical solutions. The use of R/E in observational studies requires particular cautions in terms of formal interpretation and this commentary aims at providing a practical resource for future studies assessing racial/ethnic health disparities in environmental research.
Correction to: Coincidence analysis: a new method for causal inference in implementation science
Authors: Whitaker Rebecca Garr , Sperber Nina , Baumgartner Michael , Thiem Alrik , Cragun Deborah , Damschroder Laura , Miech Edward J. , Slade Alecia , Birken Sarah
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
Influence of SCA on clinical outcomes and cervical alignment after laminoplasty in patients with multilevel cervical spondylotic myelopathy
Authors: Wang Zheng , Wang Zhi-Wei , Fan Xi-Wen , Liu Zhen , Sun Jia-Yuan , Ding Wen-Yuan , Yang Da-Long
Published: January 2021

Background

To study the impact of changes in spino-cranial angle (SCA) on sagittal alignment and to investigate the relationship between SCA and Neck Disability Index (NDI) scores after laminoplasty (LP)

Material and methods

In total, 72 patients with multilevel cervical spondylotic myelopathy (MCSM) after laminoplasty (LP) were retrospectively enrolled. Based on the optimal cut-off values of preoperative SCA, patients were classified into low SCA and high SCA groups. Radiographic data were measured, including spino-cranial angle (SCA), T1-slope (T1s), C2–7 lordosis (CA), T1s minus CA (T1sCA), and C2–7 sagittal vertical axis (cSVA). JOA and NDI scores were both applied to assess postoperative and follow-up clinical efficacy. Pearson correlation coefficient and linear regression analysis were respectively calculated between radiographic data and between SCA and NDI.

Results

The preoperative SCA was significantly correlated with T1s (r = − 0.795), CA (r = − 0.857), and cSVA (r = 0.915). A receiver operating characteristic (ROC) curve model predicted a threshold of SCA (value of 85.2°). At the follow-up period, patients with lower SCA had a higher T1s and CA and a lower cSVA, simultaneously accompanied by greater △T1s, △CA, and △cSVA. The linear regression model demonstrated that SCA in the higher group was positively correlated with NDI, and patients with higher SCA had worse NDI scores (pre: p < 0.001; post: p < 0.001; F/U: p = 0.003) and greater changes of NDI (post: p < 0.010; F/U: p = 0.002).

Conclusion

SCA may be a good predictor of evaluating sagittal balance and planning surgery. Changes in sagittal alignment in the low SCA group were affected more easily, and a higher SCA was associated with worse quality of life. Laminoplasty could be a good choice for patients with lower SCA.
FimH as a scaffold for regulated molecular recognition
Authors: Ludwig Shivani Gupta , Kiyohara Casey L. , Carlucci Laura A. , Kisiela Dagmara , Sokurenko Evgeni V. , Thomas Wendy Evelyn
Published: January 2021

Background

Recognition proteins are critical in many biotechnology applications and would be even more useful if their binding could be regulated. The current gold standard for recognition molecules, antibodies, lacks convenient regulation. Alternative scaffolds can be used to build recognition proteins with new functionalities, including regulated recognition molecules. Here we test the use of the bacterial adhesin FimH as a scaffold for regulated molecular recognition. FimH binds to its native small molecule target mannose in a conformation-dependent manner that can be regulated by two types of noncompetitive regulation: allosteric and parasteric.

Results

We demonstrate that conformational regulation of FimH can be maintained even after reengineering the binding site to recognize the non-mannosylated targets nickel or Penta-His antibody, resulting in an up to 7-fold difference in KDbetween the two conformations. Moreover, both the allosteric and parasteric regulatory mechanisms native to FimH can be used to regulate binding to its new target. In one mutant, addition of the native ligand mannose parasterically improves the mutant’s affinity for Penta-His 4-fold, even as their epitopes overlap. In another mutant, the allosteric antibody mab21 reduces the mutant’s affinity for Penta-His 7-fold. The advantage of noncompetitive regulation is further illustrated by the ability of this allosteric regulator to induce 98% detachment of Penta-His, even with modest differences in affinity.

Conclusions

This illustrates the potential of FimH, with its deeply studied conformation-dependent binding, as a scaffold for conformationally regulated binding via multiple mechanisms.
Resequencing of global Tartary buckwheat accessions reveals multiple domestication events and key loci associated with agronomic traits
Authors: Zhang Kaixuan , He Ming , Fan Yu , Zhao Hui , Gao Bin , Yang Keli , Li Faliang , Tang Yu , Gao Qiang , Lin Tao , Quinet Muriel , Janovská Dagmar , Meglič Vladimir , Kwiatkowski Jacek , Romanova Olga , Chrungoo Nikhil , Suzuki Tatsuro , Luthar Zlata , Germ Mateja , Woo Sun-Hee , Georgiev Milen I. , Zhou Meiliang
Published: January 2021

Background

Tartary buckwheat (Fagopyrum tataricum) is a nutritionally balanced and flavonoid-rich crop plant that has been in cultivation for 4000 years and is now grown globally. Despite its nutraceutical and agricultural value, the characterization of its genetics and its domestication history is limited.

Results

Here, we report a comprehensive database of Tartary buckwheat genomic variation based on whole-genome resequencing of 510 germplasms. Our analysis suggests that two independent domestication events occurred in southwestern and northern China, resulting in diverse characteristics of modern Tartary buckwheat varieties. Genome-wide association studies for important agricultural traits identify several candidate genes, includingFtUFGT3andFtAP2YT1that significantly correlate with flavonoid accumulation and grain weight, respectively.

Conclusions

We describe the domestication history of Tartary buckwheat and provide a detailed resource of genomic variation to allow for genomic-assisted breeding in the improvement of elite cultivars.
Trematode diversity reflecting the community structure of Danish freshwater systems: molecular clues
Authors: Duan Yajiao , Al-Jubury Azmi , Kania Per Walter , Buchmann Kurt
Published: January 2021

Background

Digenean trematodes are parasitic platyhelminths that use several hosts in their life cycles and are thereby embedded in various ecosystems affected by local environmental conditions. Their presence in a habitat will reflect the presence of different host species and, as such, they can serve as ecological indicators. Only limited information on the occurrence of trematodes and their link to other trophic levels in the Danish freshwater ecosystems is currently available.Therefore, the main aim of the present study was to increase our knowledge in this field.

Methods

Snails were sampled from 21 freshwater lakes in Denmark, following which shedding procedures were performed, cercariae were recoved and the released parasites were identified using molecular tools (PCR and sequencing).

Results

A total of 5657 snail hosts belonging to ten species were identified, revealing a highly diverse parasite fauna comprising 22 trematode species. The overall trematode prevalence was 12.6%, but large variations occurred between host species. The snail host Lymnaea stagnalis showed the highest prevalence and also exhibited the highest diversity, accounting for 47.6% of the species richness.

Conclusions

This survey contributes updated information on parasite–host relations and compatibility and may assist in describing the ecological structure of the investigated Danish freshwater ecosystems.

Graphical Abstract
Photoacoustic and high-frequency ultrasound imaging of systemic sclerosis patients
Authors: Daoudi Khalid , Kersten Brigit E. , van den Ende Cornelia H. M. , van den Hoogen Frank H. J. , Vonk Madelon C. , de Korte Chris L.
Published: January 2021

Introduction

Systemic sclerosis starts with an early phase characterized by Raynaud’s phenomenon, puffy fingers/hands, autoantibodies, and a scleroderma nailfold microscopic pattern. Alterations in the nailfold microscopic pattern are not evident in all early SSc patients. Photoacoustics (PA) and high-frequency ultrasound (HFUS) could fulfill this need. The former can measure oxygen saturation while the latter can measure skin thickening. We hypothesize that photoacoustics and high-frequency ultrasound can distinguish (early) SSc patients from individuals with primary Raynaud’s phenomenon (PRP) by measuring oxygenation of the fingertip and skin thickening.

Methods

We compared measurements of oxygenation and skin thickness of the third finger between (early) SSc patients and PRP individuals and healthy controls. The spearman rank correlation was used to analyze an association between capillary density and oxygen saturation of the fingers.

Results

Thirty-one adult subjects participated in this study: twelve patients with SSc, 5 patients with early SSc, 5 volunteers with PR, and 9 healthy controls.

We found a significant difference in oxygen saturation between (early) SSc patients (80.8% ± 8.1 and 77.9% ± 10.5) and individuals with PRP (93.9% ± 1.1).

Measurements of skin thickening showed a significant difference in (early) SSc patients compared to individuals with PRP (0.48 ± 0.06 mm and 0.51 ± 0.16 mm vs. 0.27 ± 0.01 mm). There was no significant difference between healthy and PRP individuals in oxygenation or skin thickening.

Conclusion

Photoacoustic and high-frequency ultrasound could help to distinguish between (early) SSc, PRP, and healthy individuals in both oxygenation and skin thickening.
Overall reduced lymphocyte especially T and B subsets closely related to the poor prognosis and the disease severity in severe patients with COVID-19 and diabetes mellitus
Authors: Liu Dafeng , Wang Yong , Zhao Bennan , Lan Lijuan , Liu Yaling , Bao Lei , Chen Hong , Yang Min , Li Qingfeng , Zeng Yilan
Published: January 2021

Background

A dysregulated host immune response is common in patients with COVID-19.

Aim

In this study, we aimed to define the characteristics of lymphocyte subsets and their relationship with disease progression in COVID-19 patients with or without diabetes mellitus (DM).

Methods

The baseline peripheral lymphocyte subsets were compared between 55 healthy controls and 95 patients with confirmed COVID-19, and between severe and non-severe COVID-19 patients with or without DM.

Results

The prevalence of DM in the COVID-19 group was 20%, and patients with severe COVID-19 had a higher prevalence of DM than those with non-severe disease (P = 0.006). Moreover, a significantly poor prognosis and a higher rate of severity were found in those with DM relative to those without DM (P = 0.001, 0.003). Generally, all lymphocytes and subsets of lymphocytes, especially B and T cells, were significant reduced in COVID-19 patients, particularly in those with DM. Patients with severe COVID-19 and DM had the lowest lymphocyte counts compared with those with severe COVID-19 without DM, and those with non-severe COVID-19 with or without DM. Partially decreased lymphocyte subsets, age and DM were closely related to disease progression and prognosis.

Conclusions

These findings provide a reference for clinicians that immunomodulatory treatment may improve disease progression and prognosis of COVID-19 patients, especially those with severe disease with DM.

Trial registration Chinese Clinical Trial Register ChiCTR2000034563
Inversion of Love waves in earthquake ground motion records for two-dimensional S-wave velocity model of deep sedimentary layers
Authors: Kasamatsu Kentaro , Yamanaka Hiroaki , Sakai Shin’ichi
Published: January 2021

We propose a new waveform inversion method to estimate the 2D S-wave velocity structure of deep sedimentary layers using broadband Love waves. As a preprocessing operation in our inversion scheme, we decompose earthquake observation records into velocity waveforms for periods of 1 s each. Then, we include in the inversion only those periods for which the assumption of 2D propagation holds, which we propose to determine through a principal component analysis. A linearized iterative inversion analysis for the selected Love wave segments filtered for periods of 1 s each allows a detailed estimation of the boundary shapes of interfaces over the seismic bedrock with an S-wave velocity of approximately 3 km/s. We demonstrate the effectiveness of the technique with applications to observed seismograms in the Kanto Plain, Japan. The differences between the estimated and existing velocity structure models are remarkable at the basin edges. Our results show remarkable differences from previous existing structural models, particularly near the basin edges while being in good agreement with the surface geology. Since a subsurface structure at a basin edge strongly affects the earthquake ground motions in a basin with the generation of surface waves, our method can provide a detailed model of a complex S-wave velocity structure at an edge part for strong ground motion prediction.