bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of Elastography for Differentiating Malignant and Benign Lymph Nodes During EBUS-TBNA
Authors: Madan Karan , Madan Manu , Iyer Hariharan , Mittal Saurabh , Madan Neha Kawatra , Rathi Vidushi , Tiwari Pavan , Hadda Vijay , Mohan Anant , Pandey Ravindra M. , Guleria Randeep
Published: June 2021

Background:

Ultrasound elastography noninvasively estimates tissue hardness. Studies have evaluated elastography for differentiating malignant from benign lymph nodes during endobronchial ultrasound-guided transbronchial needle aspiration. Several methods of performing elastography are described with variable diagnostic accuracy.

Methods:

The aim of this study was to evaluate endobronchial ultrasound-guided elastography in differentiating malignant from benign mediastinal lymphadenopathy. We performed a systematic search of the PubMed and Embase databases to extract the relevant studies. A diagnostic accuracy meta-analysis was carried out to calculate the pooled sensitivity and specificity [with 95% confidence intervals (CIs)], and positive and negative likelihood ratios of elastography.

Results:

After a systematic search, 20 studies (1600 patients, 2712 nodes) were selected. The pooled sensitivity and specificity of elastography were 0.90 (95% CI, 0.84-0.94) and 0.79 (95% CI, 0.73-0.84), respectively. The summary receiver operating curve demonstrated an area under the curve for elastography of 0.90 (0.88-0.93). The positive and negative likelihood ratios and the diagnostic odds ratio were 4.3 (95% CI, 3.3-5.5), 0.12 (95% CI, 0.07-0.20), and 35 (95% CI, 19-63), respectively. Of the most commonly described methods, the color classification method (type 3 malignant vs. type 1 benign) demonstrated the highest area under the curve of 0.91 (0.88-0.93). There was significant heterogeneity and publication bias. Subgroup analyses indicated no significant difference between the sensitivity and specificity of quantitative and qualitative elastography methods.

Conclusions:

Ultrasound elastography is useful in differentiating malignant and benign lymph nodes during endobronchial ultrasound-guided transbronchial needle aspiration. However, elastography does not replace the requirement of lymph node aspiration.
Primary Intraosseous Squamous Cell Carcinoma of the Mandible Mimicking Inflammation on FDG PET/CT
Authors: Fan Qiuping , Wang Rang , Tian Rong , Su Minggang
Published: June 2021

Primary intraosseous squamous cell carcinoma (SCC) is an uncommon malignant cancer involving the jaw bones. We herein reported the imaging findings of a primary intraosseous SCC of the mandible in a 47-year-old man. He was diagnosed as cancer of unknown primary in the cervical node. FDG PET/CT revealed a focal hypermetabolic lesion around the tooth root of the right lower molar. MRI showed the lesion had hyperintensity on T2-weighted imaging and significant enhancement on T1-weighted imaging fat saturate images. The final diagnosis of primary intraosseous SCC of mandible was confirmed pathologically.
Courtesy Authorship Practices Among First and Senior Authors
Authors: Condron Mary E. , Kibbe Melina R. , Azarow Kenneth S. , Martin Matthew J.
Published: June 2021

Objectives:

A courtesy author is an individual who has not met authorship criteria but is listed as an author. This practice is common and often seen as victimless. Because publications are used for funding and promotion decisions, it is critical to understand biases in this practice.

Methods:

An anonymous survey was conducted from March to October 2020 of first and senior authors of publications from 2014 to 2015 in 8 surgical journals. Authors were surveyed about demographic data, practice setting, and courtesy author practices.

Results:

Three hundred forty-one authors responded (16% response rate). 75% were from academic practice settings. 14% reported adding courtesy authors 5 or more times in the past year. Courtesy authors were more often male (80%, P = 0.023), older (75%), and of higher academic rank (65%) than first/senior authors. All author groups were >75% white. When a reason was reported, 46% added a courtesy author due to avoid retaliation; 64% to avoid awkwardness. 26% expected reciprocal authorship offers. 92% of respondents acknowledge understanding International Committee of Medical Journal Editors authorship criteria. Women were less common among those added from goodwill than those added from fear (P = 0.039.) When courtesy authors were of a lower rank than first/senior authors, they were nearly twice as likely to be female (P = 0.0056) or non-white (P = 0.0184.)

Conclusion:

Courtesy authors were more often male, older, and higher rank than first/senior authors. Fear of career consequences was a major motivator for including courtesy authors. Understanding the motivations and pressures leading to courtesy authorship will help to correct this practice.
Racial and Ethnic Disparities in Breast Cancer Survival
Authors: Goel Neha , Yadegarynia Sina , Lubarsky Maya , Choi Seraphina , Kelly Kristin , Balise Raymond , Kesmodel Susan B. , Kobetz Erin
Published: June 2021

Objective:

To understand the impact of Black race on breast cancer (BC) presentation, treatment, and survival among Hispanics.

Summary of Background Data:

It is well-documented that non-Hispanic Blacks (NHB) present with late-stage disease, are less likely to complete treatment, and have worse survival compared to their non-Hispanic White (NHW) counterparts. However, no data evaluates whether this disparity extends to Hispanic Blacks (HB) and Hispanic Whites (HW). Given our location in Miami, gateway to Latin America and the Caribbean, we have the diversity to evaluate BC outcomes in HB and HW.

Methods:

Retrospective cohort study of stage I-IV BC patients treated at our institution from 2005–2017. Kaplan-Meier survival curves were generated and compared using the log-rank test. Multivariable survival models were computed using Cox proportional hazards regression.

Results:

Race/ethnicity distribution of 5951 patients: 28% NHW, 51% HW, 3% HB, and 18% NHB. HB were more economically disadvantaged, had more aggressive disease, and less treatment compliant compared to HW. 5-year OS by race/ethnicity was: 85% NHW, 84.8% HW, 79.4% HB, and 72.7% NHB (P < 0.001). After adjusting for covariates, NHB was an independent predictor of worse OS [hazard ratio:1.25 (95% confidence interval: 1.01–1.52), P < 0.041)].

Conclusions:

In this first comprehensive analysis of HB and HW, HB have worse OS compared to HW, suggesting that race/ethnicity is a complex variable acting as a proxy for tumor and host biology, as well as individual and neighborhood-level factors impacted by structural racism. This study identifies markers of vulnerability associated with Black race and markers of resiliency associated with Hispanic ethnicity to narrow a persistent BC survival gap.
Early Impairment in the Ventral Visual Pathway Can Predict Conversion to Dementia in Patients With Amyloid-negative Amnestic Mild Cognitive Impairment
Authors: Kim Hyung-Ji , Cheong E-nae , Jo Sungyang , Lee Sunju , Shim Woo-Hyun , Kang Dong-Wha , Kwon Miseon , Kim Jae Seung , Lee Jae-Hong
Published: June 2021

Background:

Around 15% to 20% of patients with clinically probable Alzheimer disease have been found to have no significant Alzheimer pathology on amyloid positron emission tomography. A previous study showed that conversion to dementia from amyloid-negative mild cognitive impairment (MCI) was observed in up to 11% of patients, drawing attention to this condition.

Object:

We gathered the detailed neuropsychological and neuroimaging data of this population to elucidate factors for conversion to dementia from amyloid-negative amnestic MCI.

Methods:

This study was a single-institutional, retrospective cohort study of amyloid-negative MCI patients over age 50 with at least 36 months of follow-up. All subjects underwent detailed neuropsychological testing, 3 tesla brain magnetic resonance imaging), and fluorine-18(18F)-florbetaben amyloid positron emission tomography scans.

Results:

During the follow-up period, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairment in all visual memory tasks. The volumetric analysis revealed that the converter group had significantly reduced total hippocampal volume on the right side, gray matter volume in the right lateral temporal, lingual gyri, and occipital pole.

Conclusion:

Our study showed that reduced gray matter volume related to visual memory processing may predict clinical progression in this amyloid-negative MCI population.
Brain 18F-Florbetapir PET/CT Findings in an Early-onset Alzheimer Disease Patient Carrying Presenilin-1 G378E Mutation
Authors: Cistaro Angelina , Quartuccio Natale , Cassalia Laura , Vai Daniela , Guerra Ugo Paolo , Atzori Cristiana , Rainero Innocenzo , Imperiale Daniele
Published: June 2021

Positron emission tomography (PET) with 18F-Fluorodeoxyglucose (18F-FDG) plays an outstanding role in the diagnostic work-up of dementia. Amyloid PET imaging is a complementary imaging technique for the early detection of Alzheimer disease (AD). β-amyloid precursor protein (APP), Presenilin-1 (PSEN1) and Presenilin-2 (PSEN2) are the 3 main causative genes responsible for autosomal dominant early-onset Alzheimer disease (EOAD). This is the first report of 18F-Florbetapir amyloid imaging findings in a 35-year-old male patient with EOAD carrying the G378E mutation in PSEN1 gene. Brain computed tomography (CT) and magnetic resonance imaging scans showed remarkable cerebral atrophy with dilatation of the cerebrospinal fluid spaces; furthermore, a 18F-Florbetapir PET/CT scan demonstrated also widespread remarkable accumulation of the amyloid tracer in the cerebral cortex, with reduction of the normal contrast between white and gray matter and flattening of the external cortical margins. Furthermore, PET/CT showed intense 18F-florbetapir uptake in the striatum and in the thalamus bilaterally. Our case supports the usefulness of amyloid PET imaging in the diagnostic work-up of EOAD.
Neuromuscular complications of cancer therapy
Authors: Argyriou Andreas A. , Bruna Jordi , Mantovani Elisa , Tamburin Stefano
Published: June 2021

Purpose of review

The neuromuscular complications of cancer therapy include chemotherapy-induced peripheral neurotoxicity (CIPN), immune-related neuromuscular complications to immune checkpoint inhibitors and radiation-induced neuropathy/plexopathy. With a wider focus on CIPN, we will discuss new pathogenetic insights, recent predictive biomarkers and emerging therapies for neuromuscular complications of cancer therapy.

Recent findings

Findings from recent preclinical studies have improved our knowledge on new CIPN pathogenetic pathways, including the activation of senescence-like processes in neurons, axonal degeneration and neuroinflammation. Metabolomics and serum neurofilament light chain levels appear the most promising biomarkers to predict CIPN development and severity. There is some recent evidence of promising pharmacological compounds to prevent or treat CIPN, and new drugs are in early development and testing.

A multimodal assessment, with neurophysiological, imaging and patient-reported outcome measures, coupled with the use of reliable blood or genetic biomarkers, may offer pathogenetic grounds for future preventive and symptomatic strategies for the multidisciplinary treatment of neuromuscular complications of cancer therapy.
Bioinformatics analysis and identification of genes and molecular pathways involved in Parkinson’s disease in patients with mutations in the glucocerebrosidase gene
Authors: Xu Dan-Dan , Li Guo-Qian , Wu Zhi-Sheng , Liu Xiao-Qiang , Yang Xiao-Xia , Wang Jie-Hua
Published: June 2021

Glucocerebrosidase (GBA) mutations occur frequently in Parkinson’s disease (PD) patients. This study aims to identify potential crucial genes and pathways associated with GBA mutations in patients with PD and to further analyze new molecular mechanisms related to the occurrence of gene mutations from the perspective of bioinformatics. Gene expression profiles of datasets GSE53424 and GSE99142 were acquired from the Gene Expression Ominibus database. Differentially expressed genes (DEGs) were detected, using the ‘limma’ package in R, comparing IDI-PD 1 (idiopathic PD patients) and GBA-PD 1 [PD patients with heterozygous GBA mutations (GBA N370S)] group samples. The functions of top modules were assessed using the DAVID, whereas gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Protein–protein interaction networks were assembled with Cytoscape software and separated into subnetworks using the Molecular Complex Detection Algorithm. Data from GSE53424 and GSE99142 were also extracted to verify our findings. There were 283 DEGs identified in PD patients heterozygous for GBA mutations. Module analysis revealed that GBA mutations in PD patients were associated with significant pathways, including Calcium signaling pathway, Rap1 signaling pathway and Cytokine–cytokine receptor interaction. Hub genes of the two modules were corticotropin-releasing hormone (CRH) and Melatonin receptor 1B (MTNR1B). The expression of CRH was downregulated, whereas that of MTNR1B was upregulated in PD patients with GBA mutations. The expression of CRH and MTNR1B has diagnostic value for PD patients with heterozygous GBA mutations. Novel DEGs and pathways identified herein might provide new insights into the underlying molecular mechanisms of heterozygous GBA mutations in PD patients.
Psychosis symptoms associated with Niemann-Pick disease type C
Authors: Ong Leong Tung
Published: June 2021

Niemann-Pick disease type C (NP-C) is a severe neurovisceral lipid storage disease that results in the accumulation of unesterified cholesterol in lysosomes or endosomes. The clinical presentations of NP-C are variable which include visceral symptoms, neurologic symptoms and psychiatric symptoms. Psychosis is the most common psychiatric manifestation of NP-C and is indistinguishable from a typical psychosis presentation of schizophrenia. The common psychotic presentations in NP-C include visual hallucinations, delusions, auditory hallucinations and thought disorders. Psychosis symptoms are more common in adult or adolescent-onset forms compared with pediatric-onset forms. The underlying pathophysiology of psychosis in NP-C is most probably due to dysconnectivity particularly between frontotemporal connectivity and subcortical structures. NP-C sometimes is mistaken for schizophrenia which causes delay in treatment due to lack of awareness and literature review. This review aims to summarize the relevant case reports on psychosis symptoms in NP-C and discuss the genetics and pathophysiology underlying the condition.
Shifts in growth, but not differentiation, foreshadow the formation of exaggerated forms under chicken domestication
Authors: Núñez-León Daniel , Cordero Gerardo A. , Schlindwein Xenia , Jensen Per , Stoeckli Esther , Sánchez-Villagra Marcelo R. , Werneburg Ingmar
Published: June 2021

Domestication provides an outstanding opportunity for biologists to explore the underpinnings of organismal diversification. In domesticated animals, selective breeding for exaggerated traits is expected to override genetic correlations that normally modulate phenotypic variation in nature. Whether this strong directional selection affects the sequence of tightly synchronized events by which organisms arise (ontogeny) is often overlooked. To address this concern, we compared the ontogeny of the red junglefowl (RJF) (Gallus gallus) to four conspecific lineages that underwent selection for traits of economic or ornamental value to humans. Trait differentiation sequences in embryos of these chicken breeds generally resembled the representative ancestral condition in the RJF, thus revealing that early ontogeny remains highly canalized even during evolution under domestication. This key finding substantiates that the genetic cost of domestication does not necessarily compromise early ontogenetic steps that ensure the production of viable offspring. Instead, disproportionate beak and limb growth (allometry) towards the end of ontogeny better explained phenotypes linked to intense selection for industrial-scale production over the last 100 years. Illuminating the spatial and temporal specificity of development is foundational to the enhancement of chicken breeds, as well as to ongoing research on the origins of phenotypic variation in wild avian species.
Climate variability and parent nesting strategies influence gas exchange across avian eggshells
Authors: Attard Marie R. G. , Portugal Steven J.
Published: June 2021

Embryo survival in birds depends on a controlled transfer of water vapour and respiratory gases through the eggshell, and this exchange is critically sensitive to the surrounding physical environment. As birds breed in most terrestrial habitats worldwide, we proposed that variation in eggshell conductance has evolved to optimize embryonic development under different breeding conditions. This is the first study to take a broad-scale macro-ecological view of avian eggshell conductance, encompassing all key avian taxonomic groups, to assess how life history and climate influence the evolution of this trait. Using whole eggs spanning a wide phylogenetic diversity of birds, we determine that body mass, temperature seasonality and whether both parents attend the nest are the main determinants of eggshell conductance. Birds breeding at high latitudes, where seasonal temperature fluctuations are greatest, will benefit from lower eggshell conductance to combat temporary periods of suspended embryo growth and prevent dehydration during prolonged incubation. The nest microclimate is more consistent in species where parents take turns incubating their clutch, resulting in lower eggshell conductance. This study highlights the remarkable functional qualities of eggshells and their importance for embryo survival in extreme climates.
Dissecting heart age using cardiac magnetic resonance videos, electrocardiograms, biobanks, and deep learning
Authors: Goallec Alan Le , Prost Jean-Baptiste , Collin Sasha , Diai Samuel , Vincent Théo , Patel Chirag J.
Published: June 2021

Heart disease is the first cause of death after age 65 and, with the world population aging, its prevalence is expected to starkly increase. We used deep learning to build a heart age predictor on 45,000 heart magnetic resonance videos [MRI] and electrocardiograms [ECG] from the UK Biobank cohort (age range 45-81 years). We predicted age with a root mean squared error [RMSE] of 2.81±0.02 years (R-Squared=85.6±0.2%) and found that accelerated heart aging is heritable at more than 35%. MRI-based anatomical features predicted age better than ECG-based electro-physiological features (RMSE=2.89±0.02 years vs. 6.09±.0.02 years), and heart anatomical and electrical aging are weakly correlated (Pearson correlation=.249±.002). Our attention maps highlighted the aorta, the mitral valve, and the interventricular septum as key anatomical features driving heart age prediction. We identified genetic (e.g titin gene) and non-genetic correlates (e.g smoking) of accelerated heart aging.
A tale of two variants: Spread of SARS-CoV-2 variants Alpha in Geneva, Switzerland, and Beta in South Africa
Authors: Althaus Christian L. , Baggio Stephanie , Reichmuth Martina L. , Hodcroft Emma B. , Riou Julien , Neher Richard A. , Jacquerioz Frédérique , Spechbach Hervé , Salamun Julien , Vetter Pauline , Williamson Carolyn , Hsiao Nei-yuan , Preiser Wolfgang , Davies Mary-Ann , Lessells Richard J. , de Olivera Tulio , Kaiser Laurent , Eckerle Isabella
Published: June 2021

Several SARS-CoV-2 variants of concern (VOC) are spreading rapidly in different regions of the world. The underlying mechanisms behind their transmission advantage remain unclear. We measured viral load in 950 individuals and found that infections with variant Alpha exhibit a higher viral load and longer viral shedding compared to non-VOC. We then used a transmission model to analyze the spread of variant Alpha in Geneva, Switzerland, and variant Beta in South Africa. We estimated that Alpha is either associated with a 37% (95% compatibility interval, CI: 25–63%) increase in transmissibility or a 51% (95% CI: 32–80%) increase of the infectious duration, or a combination of the two mechanisms. Assuming 50% immune evasion for Beta, we estimated a 23% (95% CI: 10–37%) increase in transmissibility or a 38% (95% CI: 15–78%) increase of the infectious duration for this variant. Beta is expected to outgrow Alpha in regions where the level of naturally acquired immunity from previously circulating variants exceeds 20% to 40%. Close monitoring of Alpha and Beta in regions with different levels of immunity will help to anticipate the global spread of these and future variants.
Smartphone Camera Based Assessment of Adiposity: A Multi-Site Validation Study
Authors: Majmudar Maulik D. , Chandra Siddhartha , Kennedy Samantha , Agrawal Amit , Sippel Mark , Ramu Prakash , Chaudhri Apoorv , Criminisi Antonio , Smith Brooke , Heymsfield Steven B. , Stanford Fatima Cody
Published: June 2021

Background

Body composition is a key component of health in both individuals and populations, and excess adiposity is associated with an increased risk of developing chronic diseases. Body mass index (BMI) and other clinical or consumer-facing tools for quantifying body fat (BF) are often inaccurate, cost-prohibitive, or cumbersome to use. The aim of the current study was to evaluate the performance of a novel automated computer vision method, visual body composition (VBC), that uses two-dimensional photographs captured via a conventional smartphone camera to estimate percentage total body fat (%BF).

Methods

134 healthy adults ranging in age (21-76 years), sex (61.2% women), race (60.4% Caucasian; 23.9% Black), and body mass index (BMI, 18.5-51.6 kg/m2) were evaluated at two clinical sites. Each participant had %BF measured with VBC, three consumer and two professional bioimpedance analysis (BIA) systems, as well as air displacement plethysmography (ADP). %BF measured by dual-energy X-ray absorptiometry (DXA) was set as the reference against which all other estimates were compared.

Results

Relative to DXA, VBC had the lowest mean absolute error and standard deviation (2.34%±1.83%) compared to all other evaluated methods (p<0.05 for all comparisons). %BF measured by VBC also had very good concordance with DXA (Lin’s concordance correlation coefficient, CCC: overall 0.94; women 0.92; men 0.90); whereas BMI had very poor concordance (CCC: overall 0.45; women 0.40; men 0.74). Bland-Altman analysis of VBC revealed the tightest limits of agreement (LOA) and absence of significant bias relative to DXA (bias 0.85%, R2=0.01; p=0.41; LOA −4.7% to +6.4%), whereas all other evaluated methods had significant (p<0.01) bias and wider limits of agreement.

Conclusion

In this first validation study of a novel, accessible, and easy-to-use system, VBC body fat estimates were accurate and without significant bias compared to DXA as the reference; VBC performance exceeded those of all other BIA and ADP methods evaluated. The wide availability of smartphones suggests that the VBC method for evaluating %BF can play a major role in quantifying adiposity levels in a wide range of settings.

TRIAL REGISTRATION

Funded by Amazon, Inc., Seattle, WA.
Workflow Intervals andOutcomesof Endovascular Treatment for Acute Large-Vessel Occlusion During On- Versus Off-Hours in China The ANGEL-ACT Registry
Authors: Ding Yunlong , Gao Feng , Ji Yong , Zhai Tingting , Tong Xu , Jia Baixue , Wu Jian , Wu Jiaqi , Zhang Yanrong , Wei Can , Wang Wenjuan , Zhou Jue , Niu Jiali , Miao Zhongrong , Liu Yan
Published: June 2021

Background

Acute ischemic stroke (AIS) leads to a substantial burden of disease among the elderly. There may be a delay in or a poor outcome of endovascular treatment (EVT) among AIS patients with large-vessel occlusion (LVO) during off-hours. By using a prospective, nationwide registry, we compared the workflow intervals and radiological/clinical outcomes between patients with acute LVO treated with EVT presenting during off- and on-hours.

Methods

We analyzed prospectively collected Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke (ANGEL-ACT) data. Patients presenting during off-hours were defined as those presenting to the emergency department from Monday to Friday between the hours of 17:30 and 08:00, on weekends (from 17:30 on Friday to 08:00 on Monday), and on national holidays. We used logistic regression models with adjustment for potential confounders to determine independent associations between the time of presentation and outcomes.

Results

Among 1788 patients, 1079 (60.3%) presented during off-hours. The median onset-to-door time and onset-to-reperfusion time were significantly longer during off-hours than on-hours (165 vs 125 minutes, P=0.002 and 410 vs 392 minutes, P=0.027). However, there were no significant differences between patients presenting during off- and on-hours in any radiological/clinical outcomes (mRS score: 3 vs 3 points, P=0.204; mortality: 15.9% vs 14.3%, P=0.172; successful reperfusion: 88.5% vs 87.2%, P=0.579; sICH: 7.2% vs 8.4%, P=0.492).

Conclusions

Off-hours presentation in the nationwide real-world registry was associated with a delay in the visit and reperfusion time of EVT in patients with AIS. However, this delay did not lead to worse radiological/clinical outcomes.

Registraton

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939.
A Meta-Analysis of Influenza Vaccination Following Correspondence: Considerations for COVID-19
Authors: Murphy Robert P. , Taaffe Carol , Ahern Elayne , McMahon Grace , Muldoon Orla
Published: June 2021

Background

High vaccination rates are needed to protect against influenza and to end the COVID-19 pandemic. Health authorities need to know if supplementing mass communications with direct correspondence to the community would increase uptake.

Objectives

The primary objective is to determine if sending a single written message directly to individuals increases influenza vaccine uptake, and a secondary objective is to identify any identified content shown to increase influenza vaccine uptake.

Methods

PubMed, PsycInfo and Web of Science were searched for English language RCTs testing a single correspondence for members of the community in OECD countries to obtain influenza vaccination. A meta-analysis with inverse-variance, random-effects modelling was used to estimate a mean, weighted risk ratio effect size measure of vaccine uptake. Studies were quality assessed and analysis was undertaken to account for potential publication bias.

Results

Twenty-two randomized controlled trials were included covering 37 interventions. Of the 37 interventions, 32 (86%) report an increase in influenza vaccination rates. A formal meta-analysis shows that sending a single written message increases influenza vaccine uptake by 18% (RR = 1.18, 95%CI [1.13-1.22], Z = 8.56, p < .001) relative to the no contact comparator group. Analysis shows that the intervention is effective across correspondence type, age group, time, and location, and after allowing for risk of publication bias.

Limitations

The review was restricted to English language publications, and the generalizability of results across the OECD may be questioned.

Conclusions and implications

The implication for public health authorities organizing vaccination programs for influenza, and arguably also for COVID-19, is that sending written vaccination correspondence to members of the community is likely to increase uptake.

The review was not registered nor was a protocol prepared due to time sensitivity.
Validate Real-World Data-based Endpoint Measures of Cancer Treatment Outcomes
Authors: Li Qian , Zhang Hansi , Chen Zhaoyi , Guo Yi , George Thomas J , Chen Yong , Wang Fei , Bian Jiang
Published: June 2021

Recently, there is a growing interest in using real-world data (RWD) to generate real-world evidence (RWE) that complements clinical trials. Nevertheless, to quantify the treatment effects, it is important to develop meaningful RWD-based endpoints. In cancer trials, two real-world endpoints are particularly of interest: real-world overall survival (rwOS) and real-world time to next treatment (rwTTNT). In this work, we identified ways to calculate these real-world endpoints with structured EHR data, and validated these endpoints against the gold-standard measurements of these endpoints derived from linked EHR and TR data. In addition, we also examined and reported the data quality issues especially the inconsistency between the EHR and TR data. Using survival model, our result showed that patients (1) without subsequent chemotherapy or (2) with subsequent chemotherapy and longer rwTTNT, would have longer rwOS, showing the validity of using rwTTNT as a real-world surrogate marker for measuring cancer endpoints.
Role of Hemogram-Derived Ratios and Systemic-Immune Inflammation Index in Prediction of COVID-19 Progression in Egyptian Patients
Authors: Taha Sara Ibrahim , Samaan Sara Farid , Baioumy Shereen Atef , Shata Aalaa Kamal , Youssef Mariam Karam
Published: June 2021

Background

Early detection of COVID-19 patients with potentially severe disease is crucial for predicting the disease’s course and prioritizing medical resources, lowering overall disease mortality.

Objectives

To explore the role of hemogram-derived ratios and systemic-immune inflammation index (SII), in addition to C-reactive protein (CRP), in predicting COVID-19 severity and prognosis.

Methods

In this retrospective study, data were collected from the medical records of 425 COVID-19 patients. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and SII, together with the CRP, were investigated and compared.

Results

NLR, PLR, SII, and CRP increased significantly in severe cases and with ICU admission (p ≤ 0.001). But, in non-survivors only NLR and CRP were significantly elevated (p < 0.05). By interpreting area under the receiver operating characteristic curve (ROC-AUC), CRP and NLR were better predictors of disease severity (AUC: 0.7 for both), the need for ICU admission (AUC: 0.763 and 0.727, respectively) and in-hospital mortality (AUC: 0.812 and 0.75, respectively). SII was significantly associated with the risk of severe disease development (odds ratio (OR): 3.143; 95% confidence interval (CI): 1.101-8.976); CRP (OR: 2.902; CI95%: 1.342-6.273) and NLR (OR: 2.662; CI95%, 1.072-6.611) were significantly associated with ICU admission risk; and only CRP was significantly associated with in-hospital mortality risk (OR: 3.988; CI95%: 1.460-10.892).

Conclusions

Values of CRP, SII, and NLR at the time of hospital admission could be independent prognostic biomarkers to predict COVID-19 progression. The integration of CRP, SII, and NLR into prognostic nomograms may lead to improved prediction.
Social Contact Patterns and Implications for Infectious Disease Transmission: A Systematic Review and Meta-Analysis of Contact Surveys
Authors: Mousa Andria , Winskill Peter , Watson Oliver J , Ratmann Oliver , Monod Mélodie , Ajelli Marco , Diallo Aldiouma , Dodd Peter J , Grijalva Carlos G , Kiti Moses Chapa , Krishnan Anand , Kumar Rakesh , Kumar Supriya , Kwok Kin On , Lanata Claudio F , de Waroux Olivier Le Polain , Leung Kathy , Mahikul Wiriya , Melegaro Alessia , Morrow Carl D , Mossong Joël , Neal Eleanor FG , Nokes David J , Pan-ngum Wirichada , Potter Gail E , Russell Fiona M , Saha Siddhartha , Sugimoto Jonathan D , Wei Wan In , Wood Robin R , Wu Joseph T , Zhang Juanjuan , Walker Patrick GT , Whittaker Charles
Published: June 2021

Background

Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings.

Methods

Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings.

Results

Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made.

Conclusions

These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions.

Funding

This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).
Inducing Body-Weight Supported Postural Perturbations during Gait and Balance Exercises to Improve Balance after Stroke – A Pilot Study
Authors: Meyer Amanda , Cutler Erica , Hellstrand Jill , Meise Emily , Rudolf Kaitlyn , Hrdlicka Henry C. , Grevelding Peter , Nankin Matthew
Published: June 2021

Introduction

Impaired balance-regulation after stroke put patients and therapists at risk for injury during rehabilitation. Body-weight-support systems (BWSSs) minimize this risk and allow patients to safely practice balance activities during therapy. Treadmill based balance perturbation systems with BWSSs are known to improve balance in patients with age or disease related impairments. However, these stationary systems are unable accommodate complex exercises requiring more freedom of movement.

Objective

To evaluate the impact of a new balance perturbation module, which is directly integrated to a track-mounted BWSS, has on patient balance after acute stroke.

Design

Unblinded quasi-randomized controlled pilot study.

Setting

Rehabilitation centered long-term acute care hospital.

Participants

Stroke rehabilitation inpatients with an admission Berg Balance Scale (BBS) assessment score ≥21/56.

Interventions

BWSS and BWSS with perturbation (BWSS-P) training was incorporated into the participants’ regular treatment. While both groups conducted the same balance and gait activities during their treatment sessions, the BWSS-P sessions included lateral and anterior/posterior resistive or assistive balance perturbations.

Main outcome measures

BBS and Activities-Specific Balance-Confidence (ABC) assessments were the main outcome measure collected. Institutional BBS data from fiscal-year 2018, prior to installation of the track mounted BWSS, was used as a historical standard-of-care (SOC) baseline.

Results

Improved post-intervention BBS and ABC assessment scores showed all participants benefited from therapy (p≤0.0438). The BBS percent-change of the BWSS-P [mean (SD) n] [66.95% (43.78%) 14] and BWSS control [53.29% (24.13%) 15] were greater than the SOC group [28.31% (17.25%) 30] (p≤0.0178), with no difference between BWSS groups (p=0.6669); ABC percent score-changes were also similar (p≥0.8036).

Conclusions

BWSS groups demonstrated similar BBS and ABC score improvements, indicating balance perturbations are not detrimental to post-acute stroke rehabilitation and are safe to use. This data provides strong rationale for conducting a larger follow-up study to further assess if this new perturbation system provides additional benefit to stroke patient balance during rehabilitation.

Clinical Trial Registration

NCT04919161
A row-generation approach for simultaneous multiple needle trajectory planning in radiofrequency ablation
Authors: Kulkarni-Thaker Shefali , Aleman Dionne , Fenster Aaron
Published: June 2021

Radiofrequency ablation is a thermal therapy for moderately-sized cancerous tumors. A target is killed with high temperatures obtained due to the current passed through one or more electrodes (needles) inserted into it. The needles’ trajectory must be meticulously planned to prevent interference with dense organs like bone or puncturing of critical structures like veins. By approximating the thermal lesion to an ellipse, we predefine several valid needle trajectories and then solve an integer programming model to identify pairwise valid needle positions, that meet clinical criteria, using a variation of the classic set cover model. To improve the models’ tractability and scalability, we use row generation-based decomposition techniques that determines pairwise validity using two different types of cuts. Finally, we analyze target and organ-at-risk (OAR) damage using several thermal damage models. Our method is tested on 12 liver targets: three targets each with four different surgical margins. We show promising results that meet clinical guidelines while obtaining full target coverage.
Natural and cryptic peptides dominate the immunopeptidome of atypical teratoid rhabdoid tumors
Authors: Marcu Ana , Schlosser Andreas , Keupp Anne , Trautwein Nico , Johann Pascal , Wölfl Matthias , Lager Johanna , Monoranu Camelia , Walz Juliane Sarah , Henkel Lisa M. , Krauß Jürgen , Ebinger Martin , Schuhmann Martin , Thomale Ulrich , Pietsch Torsten , Klinker Erdwine , Schlegel Paul G. , Oyen Florian , Reisner Yair , Rammensee Hans-Georg , Eyrich Matthias
Published: June 2021

Abstract

Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive CNS-tumors of infancy and early childhood. Hallmark is the surprisingly simple genome with inactivating mutations or deletions in the SMARCB1 gene as the oncogenic driver. Nevertheless, AT/RTs are infiltrated by immune cells and even clonally expanded T cells. However, it is unclear, which epitopes T-cells might recognize on AT/RT cells. Here, we report a comprehensive MS-based analysis of naturally presented HLA-class-I and class-II ligands on 23 AT/RTs. Comparative HLA ligandome analysis of the HLA-ligandome revealed 55 class-I and 139 class-II tumor-exclusive peptides. No peptide originated from the SMARCB1-region. In addition, 61 HLA-class I tumor-exclusive peptide sequences derived from non-canonically translated proteins. Combination of peptides from natural and cryptic class I and class II origin gave optimal representation of tumor cell compartments. Substantial overlap existed with the cryptic immunopeptidome of glioblastomas but no concordance was found with extracranial tumors. More than 80% of AT/RT-exclusive peptides were able to successfully prime CD8+T-cells, whereas naturally occurring memory responses in AT/RT-patients could only be detected for class-II epitopes. Interestingly, >50% of AT/RT-exclusive class-II ligands were also recognized by T-cells from glioblastoma patients but not from healthy donors. These findings highlight that AT/RTs, potentially paradigmatic for other pediatric tumors with a low mutational load, present a variety of highly immunogenic HLA-class-I and class-II peptides from canonical as well as non-canonical protein sources. Inclusion of such cryptic peptides into therapeutic vaccines would enable an optimized mapping of the tumor cell surface, thereby reducing the likelihood of immune evasion.

One Sentence Summary

The HLA-ligandome of atpyical teratoid-rhabdoid tumors contains immunogenic, tumor-exclusive peptides derived from natural and cryptic source proteins.
Decreased tissue stiffness in glioblastoma by MR Elastography is associated with increased cerebral blood flow
Authors: Svensson Siri Fløgstad , Fuster-Garcia Elies , Latysheva Anna , Fraser-Green Jorunn , Nordhøy Wibeke , Darwish Omar Isam , Hovden Ivar Thokle , Holm Sverre , Vik-Mo Einar O. , Sinkus Ralph , Emblem Kyrre Eeg
Published: June 2021

PURPOSE

Understanding how mechanical properties relate to functional changes in glioblastomas may help explain different treatment response between patients. The aim of this study was to map differences in biomechanical and functional properties between tumor and healthy tissue, to assess any relationship between them and to study their spatial distribution.

METHODS

Ten patients with glioblastoma and 17 healthy subjects were scanned using MR Elastography, perfusion and diffusion MRI. Stiffness and viscosity measurements G′ and G′′, cerebral blood flow (CBF), apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in patients’ contrast-enhancing tumor, necrosis, edema, and gray and white matter, and in gray and white matter for healthy subjects. A regression analysis was used to predict CBF as a function of ADC, FA, G′ and G′′.

RESULTS

Median G′ and G′′ in contrast-enhancing tumor were 13% and 37% lower than in normal-appearing white matter (P<0.01), and 8% and 6% lower in necrosis than in contrast-enhancing tumor, respectively (P<0.05). Tumors showed both inter-patient and intra-patient heterogeneity. Measurements approached values in normal-appearing tissue when moving outward from the tumor core, but abnormal tissue properties were still present in regions of normal-appearing tissue. Using both a linear and a random-forest model, prediction of CBF was improved by adding MRE measurements to the model (P<0.01).

CONCLUSIONS

The inclusion of MRE measurements in statistical models helped predict perfusion, with stiffer tissue associated with lower perfusion values.
Xpert MTB/RIF Ultra is highly sensitive for the diagnosis of tuberculosis lymphadenitis in an HIV-endemic setting
Authors: Minnies Stephanie , Reeve Byron W.P. , Rockman Loren , Nyawo Georgina , Naidoo Charissa C. , Kitchin Natasha , Rautenbach Cornelia , Wright Colleen A. , Whitelaw Andrew , Schubert Pawel , Warren Robin M. , Theron Grant
Published: June 2021

Background

Tuberculosis lymphadenitis (TBL) is the most common extrapulmonary TB (EPTB) manifestation. Xpert MTB/RIF Ultra (Ultra) is a World Health Organization-endorsed diagnostic test, but performance data for TBL, including on non-invasive specimens, are limited.

Methods

Fine needle aspiration biopsies (FNABs) from outpatients (≥18 years) with presumptive TBL (n=135) underwent: 1) routine Xpert (later Ultra once programmatically available), 2) a MGIT960 culture (if Xpert- or Ultra-negative, or rifampicin-resistant), and 3) study Ultra. Concentrated paired urine underwent Ultra. Primary analyses used a microbiological reference standard (MRS).

Results

In a head-to-head comparison (n=92) of FNAB study Ultra and Xpert, Ultra had increased sensitivity [91% (95% confidence interval 79, 98) vs. 72% (57, 84); p=0.016] and decreased specificity [76% (61, 87) vs. 93% (82, 99); p=0.020], and detected patients not on treatment. HIV nor alternative reference standards affected sensitivity and specificity. In patients with both routine and study Ultras, the latter detected more cases [+20% (0, 42); p=0.034] and, further indicative of potential laboratory-based room-for-improvement, false-negative study Ultras had more PCR inhibition than true-positives. Study Ultra “false-positives” had less mycobacterial DNA than “true-positives” [trace-positive proportions 59% (13/22) vs. 12% (5/51); p<0.001]. Exclusion or recategorization of “traces” removed potential benefits offered over Xpert. Urine Ultra had low sensitivity [18% (7, 35)].

Conclusions

Ultra on FNABs is highly sensitive and detects more TBL than Xpert. Patients with FNAB Ultra-positive “trace” results, most of whom will be culture-negative, may require additional clinical investigation. Urine Ultra could reduce the number of patients needing invasive sampling.
Retention in care and viral suppression after same-day ART initiation: One-year outcomes of the SLATE I and II individually randomized clinical trials in South Africa
Authors: Maskew Mhairi , Brennan Alana T , Fox Matthew P , Vezi Lungisile , Venter Willem DF , Rosen Sydney
Published: June 2021

Introduction

Same-day initiation (SDI) of antiretroviral therapy (ART) for HIV consistently increases ART uptake, but concerns remain about higher attrition from care after initiation. We analysed twelve-month retention in the SLATE SDI trials.

Methods

SLATE I and SLATE II were individually randomized trials at public outpatient clinics in Johannesburg that enrolled patients not yet on ART and administered the SLATE I or II algorithm, which included a symptom self-report, medical history, brief physical examination, and readiness questionnaire, to assess eligibility for SDI. ART uptake and early retention have been reported. Using routine clinic records, we conducted a pooled analysis of retention in care and HIV viral suppression 14 months after study enrolment.

Results and discussion

We enrolled 1,193 study participants (standard arms, n=599, 50%; intervention arms, n=594, 50%) and analysed by originally assigned groups. By 14 months after study enrolment (equivalent to 12-month retention in care), 50% of intervention arm patients and 46% of standard arm patients remained in care at the initiating site (crude risk difference 4% (95% confidence interval −1% to 10%; crude relative risk 1.10 (0.97-1.23), with similar viral suppression between arms. Observed attrition from care at site by 14 months was high in both study arms, but we found no evidence that the offer of SDI led to greater overall attrition or lower rates of viral suppression one year after starting ART and may have led to small improvements. Same-day initiation may have shifted some attrition from before to after dispensing of the first dose of medication.

Conclusions

An offer of same-day initiation of ART, following a carefully designed protocol to identify patients who are eligible and ready to start treatment, is not inherently associated with an overall increase in patient attrition from care.

Trial registration

Clinicaltrials.govNCT02891135, registered September 1, 2016. First participant enrolled March 6, 2017 in South Africa.Clinicaltrials.govNCT03315013, registered October 19, 2017. First participant enrolled 14 March 2018.