bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological stress in safer cycling in older age (SiFAr-stress): effect of a multicomponent exercise intervention—a study protocol for a randomized controlled trial
Authors: Britting Sabine , Kob Robert , Sieber Cornel Christian , Rohleder Nicolas , Freiberger Ellen , Becker Linda
Published: August 2021

Background

SiFAr-Stress investigates the impact of cycling on stress levels in older adults. Uncertainty due to change to motorized bicycle or fear of falling can be perceived as stressors for cyclists. Stress activates different physiological signal cascades and stimulates the hypothalamic-pituitary-adrenal (HPA) axis, which leads to the release of the stress hormone cortisol and further effects such as the development of low-grade inflammation. Both can—in the long term—be associated with negative health outcomes. The aim of the study SiFAr-Stress is to analyze inflammatory processes as well as the activity of stress systems before and after a cycling intervention for older adults.

Methods

In this study, community-dwelling older adults aged 65 years and older will be randomly assigned to either a cycling or a control intervention in a parallel-group design. Objective HPA axis–related measures (saliva cortisol and hair cortisol) will be assessed before, after, and 6–9 months after the cycling and control intervention (T0, T1, and T2). Furthermore, changes in cortisol reactivity in response to the cycling intervention will be investigated at the second and seventh training lessons. Furthermore, secondary outcomes (fear of falling, perceived stress, salivary alpha amylase, and C-reactive protein) will be assessed at T0, T1, and T2.

Discussion

The study will be the first, in which stress- and health-related bio-physiological outcomes will be assessed in the context of a multicomponent exercise intervention, addressing cycling in older adults. It will enable us to better understand the underlying patho-physiological and psychological mechanisms and will help to improve interventions for this target group.

Trial registration

ClinicalTrials.govNCT04362514. Prospectively registered on 27 April 2020
Effective recruitment strategies in an exercise trial for patients with fibromyalgia
Authors: Park Michelle , Bannuru Raveendhara R. , Price Lori Lyn , Harvey William F. , Driban Jeffrey B. , Wang Chenchen
Published: August 2021

Background

Recruitment of fibromyalgia populations into long-term clinical trials involving exercise interventions is a challenge. We evaluated the cost and randomization yields of various recruitment methods used for a fibromyalgia trial in an urban setting. We also investigated differences in participant characteristics and exercise intervention adherence based on recruitment source.

Methods

We recruited individuals with fibromyalgia in the greater Boston area to a randomized controlled trial (RCT) using six recruitment strategies: newspaper advertisements, web advertisements, flyers, clinic referrals, direct mailing to patients in a clinic database, and word of mouth. We used the American College of Rheumatology 1990 and 2010 diagnostic criteria to screen and enroll participants. During an initial phone call to an interested participant, the study staff asked how they heard about the study. In this study, we compared the cost and yield of the six recruitment strategies as well as baseline characteristics, adherence, and attendance rates of participants across strategies.

Results

Our recruitment resulted in 651 prescreens, 272 screening visits, and 226 randomized participants. Advertisements in a local commuter newspaper were most effective, providing 113 of 226 randomizations, albeit high cost ($212 per randomized participant). Low-cost recruitment strategies included clinical referrals and web advertisements, but they only provided 32 and 16 randomizations. Community-based strategies including advertisement and flyers recruited a more racially diverse participant sample than clinic referrals and mailing or calling patients. There was no evidence of difference in adherence among participants recruited from various strategies.

Conclusions

Newspaper advertisement was the most effective and most expensive method per randomized participant for recruiting large numbers of individuals with fibromyalgia in an urban setting. Community-based strategies recruited a more racially diverse cohort than clinic-based strategies.

Trial registration

ClinicalTrials.govNCT01420640. Registered on 19 August 2011.
Internet-based stress recovery intervention FOREST for healthcare staff amid COVID-19 pandemic: study protocol for a randomized controlled trial
Authors: Jovarauskaite Lina , Dumarkaite Austeja , Truskauskaite-Kuneviciene Inga , Jovaisiene Ieva , Andersson Gerhard , Kazlauskas Evaldas
Published: August 2021

Background

The demand for care during the COVID-19 pandemic has affected the mental health of healthcare workers (HCWs), thus increasing the need for psychosocial support services. Internet-based interventions have previously been found to reduce occupational stress. The study aims to test the effects of an Internet-based stress recovery intervention—FOREST—among HCWs.

Methods

A randomized controlled trial (RCT) parallel group design with three measurement points will be conducted to assess the efficacy of an Internet-based stress recovery intervention FOREST for nurses. The FOREST intervention is a 6-week Internet-based CBT and mindfulness-based program which comprises of six modules: (1) Introduction, (2) Detachment (relaxation and sleep), (3) Distancing, (4) Mastery (challenge), (5) Control, and (6) Keeping the change alive. We will compare the intervention against a waiting list group at pre-test, post-test, and follow-up. Stress recovery, PTSD, complex PTSD, moral injury, the level of stress, depression, anxiety, and psychological well-being will be measured.

Discussion

The study will contribute to the development of mental healthcare programs for the HCWs. Based on the outcomes of the study, the FOREST intervention can be further developed or offered to healthcare staff as a tool to cope with occupational stress.

Trial registration

ClinicalTrials.gov NCT04817995. Registered on 30 March 2021
Postoperative 20% albumin vs standard care and acute kidney injury after high-risk cardiac surgery (ALBICS): study protocol for a randomised trial
Authors: Balachandran Mayurathan , Banneheke Piyusha , Pakavakis Adrian , Al-Bassam Wisam , Sarode Vineet , Rowland Michael , Shehabi Yahya
Published: August 2021

Background

Acute kidney injury (AKI) is a common complication of cardiac surgery. Factors such as cardiopulmonary bypass, aortic cross-clamping and surgical stress may precipitate renal hypoperfusion and ischaemia, inflammation and oxidative stress are associated with development of AKI. Albumin’s pharmacological properties and widespread availability have the potential to mitigate these factors. However, the effect of albumin on cardiac surgery-associated AKI is unknown.

Objective

To evaluate the impact of postoperative 20% albumin infusion on kidney function after high-risk cardiac surgery.

Methods

We designed an open-label, multicentre, randomised controlled trial—the ALBICS study (ALBumin Infusion and acute kidney injury following Cardiac Surgery). A total of 590 patients undergoing high-risk cardiac surgery (combined procedure or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) will be enrolled into the study and randomly allocated to receive a postoperative 20% albumin infusion or standard care in a 1:1 ratio, stratified by centre and baseline renal function. The study fluid will be administered upon arrival in intensive care for 15 h. Patients will be followed up until 28 days after surgery or until discharge from the hospital. The primary outcome is the proportion of patients who develop AKI in both groups. Secondary outcomes to be measured are proportions of AKI stage II and III, 28-day mortality, mechanical ventilation time and length of stay in intensive care and hospital.

Conclusion

This trial aims to determine if a postoperative infusion of concentrated albumin reduces the risk of AKI following high-risk cardiac surgery.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12619001355167. Registered on 03 October 2019—retrospectively registered.https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378383.
Comparative analysis of the transcriptional responses of five Leishmania species to trivalent antimony
Authors: Medina Julián , Cruz-Saavedra Lissa , Patiño Luz Helena , Muñoz Marina , Ramírez Juan David
Published: August 2021

Background

Leishmaniasis is a neglected tropical disease caused by several species of Leishmania. The resistance phenotype of these parasites depends on the characteristics of each species, which contributes to increased therapeutic failures. Understanding the mechanism used by the parasite to survive under treatment pressure in order to identify potential common and specific therapeutic targets is essential for the control of leishmaniasis. The aim of this study was to investigate the expression profiles and potential shared and specific resistance markers of the main Leishmania species of medical importance [subgenus L. (Leishmania): L. donovani, L. infantum and L. amazonensis; subgenus L. (Viannia): L. panamensis and L. braziliensis)] resistant and sensitive to trivalent stibogluconate (SbIII).

Methods

We conducted comparative analysis of the transcriptomic profiles (only coding sequences) of lines with experimentally induced resistance to SbIII from biological replicates of five Leishmania species available in the databases of four articles based on ortholog attribution. Simultaneously, we carried out functional analysis of ontology and reconstruction of metabolic pathways of the resulting differentially expressed genes (DEGs).

Results

Resistant lines for each species had differential responses in metabolic processes, compound binding, and membrane components concerning their sensitive counterpart. One hundred and thirty-nine metabolic pathways were found, with the three main pathways comprising cysteine and methionine metabolism, glycolysis, and the ribosome. Differentially expressed orthologous genes assigned to species-specific responses predominated, with 899 self-genes. No differentially expressed genes were found in common among the five species. Two common upregulated orthologous genes were found among four species (L. donovani, L. braziliensis, L. amazonensis, and L. panamensis) related to an RNA-binding protein and the NAD(P)H cytochrome-B5-oxidoreductase complex, associated with transcriptional control and de novo synthesis of linoleic acid, critical mechanisms in resistance to antimonials.

Conclusion

Herein, we identified potential species-specific genes related to resistance to SbIII. Therefore, we suggest that future studies consider a treatment scheme that is species-specific. Despite the limitations of our study, this is the first approach toward unraveling the pan-genus genetic mechanisms of resistance in leishmaniasis.

Graphical Abstract
Burden of malaria in children under five and caregivers’ health-seeking behaviour for malaria-related symptoms in artisanal mining communities in Ghana
Authors: Dao Francois , Djonor Sampson Kafui , Ayin Christian Teye-Muno , Adu George Asumah , Sarfo Bismark , Nortey Pricillia , Akuffo Kwadwo Owusu , Danso-Appiah Anthony
Published: August 2021

Background

Artisanal mining creates enabling breeding ground for the vector of malaria parasites. There is paucity of data on the effects of artisanal mining on malaria. This study assessed burden of malaria and caregivers’ health-seeking behaviour for children under five in artisanal mining communities in East Akim District in Ghana.

Methods

A cross-sectional study involving caregivers and their children under five was conducted in three artisanal mining communities in the East Akim District in Ghana. Caregivers were interviewed using a structured questionnaire. Finger prick blood samples were collected and analysed for haemoglobin concentration using a rapid diagnostic test, and thick and thin blood smears were analysed to confirm the presence of malaria parasites.

Results

Of the 372 children under 5 years included in the study, 197 (53.1%) were male, with a mean age (± SD) of 23.0 ± 12.7 months. The proportion of children with malaria (Plasmodium falciparum and P. malariae) was 98.1% and 1.9%, respectively, whilst the proportion with anaemia (Hb < 11.0 g/dl) was 39.5% (n = 147). Almost all caregivers were female (98.9%), and 28.6% (n = 106) did not have access to any malaria control information. Caregivers associated malaria infection with mosquito bites (68.3%, n = 254) and poor sanitation (21.2%, n = 79). Malaria in children under five was significantly associated with anaemia (OR 11.07, 95% CI 6.59–18.68, n = 111/160, 69.4%; P < 0.0001), residing close to stagnant water (≤ 25 m) from an artisanal mining site (AOR 2.91, 95% CI 1.47–5.76, P = 0.002) and caregiver age younger than 30 years (OR 0.44, 95% CI 0.208–0.917, n = 162, 43.55%, P = 0.001).

Conclusions

There is a high burden of malaria and anaemia among children under five in artisanal mining communities of the East Akim District, and far higher than in non-artisanal mining sites. Interventions are needed to effectively regulate mining activities in these communities, and strengthen malaria control and health education campaigns to curtail the high malaria burden and improve health-seeking behaviour.

Graphical abstract
Characterizing parasitic nematode faunas in faeces and soil using DNA metabarcoding
Authors: Davey Marie Louise , Utaaker Kjersti Selstad , Fossøy Frode
Published: August 2021

Background

Gastrointestinal parasitic nematodes can impact fecundity, development, behaviour, and survival in wild vertebrate populations. Conventional monitoring of gastrointestinal parasitic nematodes in wild populations involves morphological identification of eggs, larvae, and adults from faeces or intestinal samples. Adult worms are typically required for species-level identification, meaning intestinal material from dead animals is needed to characterize the nematode community with high taxonomic resolution. DNA metabarcoding of environmental samples is increasingly used for time- and cost-effective, high-throughput biodiversity monitoring of small-bodied organisms, including parasite communities. Here, we evaluate the potential of DNA metabarcoding of faeces and soil samples for non-invasive monitoring of gastrointestinal parasitic nematode communities in a wild ruminant population.

Methods

Faeces and intestines were collected from a population of wild reindeer, and soil was collected both from areas showing signs of animal congregation, as well as areas with no signs of animal activity. Gastrointestinal parasitic nematode faunas were characterized using traditional morphological methods that involve flotation and sedimentation steps to concentrate nematode biomass, as well as using DNA metabarcoding. DNA metabarcoding was conducted on bulk samples, in addition to samples having undergone sedimentation and flotation treatments.

Results

DNA metabarcoding and morphological approaches were largely congruent, recovering similar nematode faunas from all samples. However, metabarcoding provided higher-resolution taxonomic data than morphological identification in both faeces and soil samples. Although concentration of nematode biomass by sedimentation or flotation prior to DNA metabarcoding reduced non-target amplification and increased the diversity of sequence variants recovered from each sample, the pretreatments did not improve species detection rates in soil and faeces samples.

Conclusions

DNA metabarcoding of bulk faeces samples is a non-invasive, time- and cost-effective method for assessing parasitic nematode populations that provides data with comparable taxonomic resolution to morphological methods that depend on parasitological investigations of dead animals. The successful detection of parasitic gastrointestinal nematodes from soils demonstrates the utility of this approach for mapping distribution and occurrences of the free-living stages of gastrointestinal parasitic nematodes.

Graphical abstract
Lower objectively and subjectively assessed numeracy are both associated with poorer self-rated health
Authors: Benda Natalie C. , Yang Zihan , Li Haojia , Zhang Tianran , Ancker Jessica S.
Published: August 2021

Objective

To compare an objective with a subjective numeracy assessment for association with self-reported health status, where numeracy refers to “the degree to which individuals have the capacity to access, process, interpret, communicate, and act on numerical, quantitative, graphical, biostatistical, and probabilistic health information needed to make effective health decisions”

Results

We completed a secondary analysis of two population-based surveys, the Empire State Poll (n = 763) and the Program for the International Assessment of Adult Competencies (PIAAC; n = 2609). The first survey assessed numeracy with a 3-item subjective instrument. The second assessed numeracy with more than 20 math problems. Both used the same measure for self-reported health status. Lower numeracy, whether subjectively or objectively assessed, was associated with worse self-reported health, even after controlling for education and other sociodemographic confounders. The odds ratios for the association were very similar (0.91 and 0.90 respectively). A lengthy objective numeracy assessment and a brief self-report assessment had similar associations with health status. A brief self-report measure of numeracy has similar properties to a lengthy objective assessment and is likely to be more feasible to use to screen patients in practice.
Identifying causal models between genetically regulated methylation patterns and gene expression in healthy colon tissue
Authors: Díez-Villanueva Anna , Jordà Mireia , Carreras-Torres Robert , Alonso Henar , Cordero David , Guinó Elisabet , Sanjuan Xavier , Santos Cristina , Salazar Ramón , Sanz-Pamplona Rebeca , Moreno Victor
Published: August 2021

Background

DNA methylation is involved in the regulation of gene expression and phenotypic variation, but the inter-relationship between genetic variation, DNA methylation and gene expression remains poorly understood. Here we combine the analysis of genetic variants related to methylation markers (methylation quantitative trait loci: mQTLs) and gene expression (expression quantitative trait loci: eQTLs) with methylation markers related to gene expression (expression quantitative trait methylation: eQTMs), to provide novel insights into the genetic/epigenetic architecture of colocalizing molecular markers.

Results

Normal mucosa from 100 patients with colon cancer and 50 healthy donors included in the Colonomics project have been analyzed. Linear models have been used to find mQTLs and eQTMs within 1 Mb of the target gene. From 32,446 eQTLs previously detected, we found a total of 6850 SNPs, 114 CpGs and 52 genes interrelated, generating 13,987 significant combinations of co-occurring associations (meQTLs) after Bonferromi correction. Non-redundant meQTLs were 54, enriched in genes involved in metabolism of glucose and xenobiotics and immune system. SNPs in meQTLs were enriched in regulatory elements (enhancers and promoters) compared to random SNPs within 1 Mb of genes. Three colorectal cancer GWAS SNPs were related to methylation changes, and four SNPs were related to chemerin levels. Bayesian networks have been used to identify putative causal relationships among associated SNPs, CpG and gene expression triads. We identified that most of these combinations showed the canonical pathway of methylation markers causes gene expression variation (60.1%) or non-causal relationship between methylation and gene expression (33.9%); however, in up to 6% of these combinations, gene expression was causing variation in methylation markers.

Conclusions

In this study we provided a characterization of the regulation between genetic variants and inter-dependent methylation markers and gene expression in a set of 150 healthy colon tissue samples. This is an important finding for the understanding of molecular susceptibility on colon-related complex diseases.
DNA methylome profiling reveals epigenetic regulation of lipoprotein-associated phospholipase A2 in human vulnerable atherosclerotic plaque
Authors: Li Jingjin , Zhang Xiaoping , Yang Mengxi , Yang Hang , Xu Ning , Fan Xueqiang , Liu Gang , Jiang Xintong , Fan Jiasai , Zhang Lifang , Zhang Hu , Zhou Ying , Li Rui , Gao Si , Jin Jiangli , Jin Zening , Zheng Jingang , Tu Qiang , Ren Jingyi
Published: August 2021

Background

Atherosclerotic plaque vulnerability is a key feature of atheroprogression and precipitating acute cardiovascular events. Although the pivotal role of epigenetic regulation in atherosclerotic plaque destabilization is being recognized, the DNA methylation profile and its potential role in driving the progression and destabilization of atherosclerotic cardiovascular disease remains largely unknown. We conducted a genome-wide analysis to identify differentially methylated genes in vulnerable and non-vulnerable atherosclerotic lesions to understand more about pathogenesis.

Results

We compared genome-wide DNA methylation profiling between carotid artery plaques of patients with clinically symptomatic (recent stroke or transient ischemic attack) and asymptomatic disease (no recent stroke) using Infinium Methylation BeadChip arrays, which revealed 90,368 differentially methylated sites (FDR < 0.05, |delta beta|> 0.03) corresponding to 14,657 annotated genes. Among these genomic sites, 30% were located at the promoter regions and 14% in the CpG islands, according to genomic loci and genomic proximity to the CpG islands, respectively. Moreover, 67% displayed hypomethylation in symptomatic plaques, and the differentially hypomethylated genes were found to be involved in various aspects of inflammation. Subsequently, we focus on CpG islands and revealed 14,596 differentially methylated sites (|delta beta|> 0.1) located at the promoter regions of 7048 genes. Integrated analysis of methylation and gene expression profiles identified that 107 genes were hypomethylated in symptomatic plaques and showed elevated expression levels in both advanced plaques and ruptured plaques. The imprinted gene PLA2G7, which encodes lipoprotein-associated phospholipase A2 (Lp-PLA2), was one of the top hypomethylated genes with an increased expression upon inflammation. Further, the hypomethylated CpG site at the promoter region of PLA2G7 was identified as cg11874627, demethylation of which led to increased binding of Sp3 and expression of Lp-PLA2 through bisulfate sequencing, chromatin immunoprecipitation assay and enzyme-linked immunosorbent assay. These effects were further enhanced by deacetylase.

Conclusion

Extensive DNA methylation modifications serve as a new and critical layer of biological regulation that contributes to atheroprogression and destabilization via inflammatory processes. Revelation of this hitherto unknown epigenetic regulatory mechanism could rejuvenate the prospects of Lp-PLA2 as a therapeutic target to stabilize the atherosclerotic plaque and reduce clinical sequelae.
A preliminary study of synthetic magnetic resonance imaging in rectal cancer: imaging quality and preoperative assessment
Authors: Zhao Li , Liang Meng , Wu Pu-yeh , Yang Yang , Zhang Hongmei , Zhao Xinming
Published: August 2021

Purpose

To compare the imaging quality, T stage and extramural venous invasion (EMVI) evaluation between the conventional and synthetic T2-weighted imaging (T2WI), and to investigate the role of quantitative values obtained from synthetic magnetic resonance imaging (MRI) for assessing nodal staging in rectal cancer (RC).

Methods

Ninety-four patients with pathologically proven RC who underwent rectal MRI examinations including synthetic MRI were retrospectively recruited. The image quality of conventional and synthetic T2WI was compared regarding signal-to-noise ratio (SNR), contrast-to-noise (CNR), sharpness of the lesion edge, lesion conspicuity, absence of motion artifacts, and overall image quality. The accuracy of T stage and EMVI evaluation on conventional and synthetic T2WI were compared using the Mc-Nemar test. The quantitative T1, T2, and PD values were used to predict the nodal staging of MRI-evaluated node-negative RC.

Results

There were no statistically significant differences between conventional and synthetic T2WI in SNR, CNR, overall image quality, lesion conspicuity, and absence of motion artifacts (p = 0.058–0.978). There were no significant differences in the diagnostic accuracy of T stage and EMVI between conventional and synthetic T2WI from two observers (p = 0.375 and 0.625 for T stage; p = 0.625 and 0.219 for EMVI). The T2 value showed good diagnostic performance for predicting the nodal staging of RC with the area under the receiver operating characteristic, sensitivity, specificity, and accuracy of 0.854, 90.0%, 71.4%, and 80.3%, respectively.

Conclusions

Synthetic MRI may facilitate preoperative staging and EMVI evaluation of RC by providing synthetic T2WI and quantitative maps in one acquisition.
Preselection of robust radiomic features does not improve outcome modelling in non-small cell lung cancer based on clinical routine FDG-PET imaging
Authors: Oliveira Carol , Amstutz Florian , Vuong Diem , Bogowicz Marta , Hüllner Martin , Foerster Robert , Basler Lucas , Schröder Christina , Eboulet Eric I. , Pless Miklos , Thierstein Sandra , Peters Solange , Hillinger Sven , Tanadini-Lang Stephanie , Guckenberger Matthias
Published: August 2021

Background

Radiomics is a promising tool for identifying imaging-based biomarkers. Radiomics-based models are often trained on single-institution datasets; however, multi-centre imaging datasets are preferred for external generalizability owing to the influence of inter-institutional scanning differences and acquisition settings. The study aim was to determine the value of preselection of robust radiomic features in routine clinical positron emission tomography (PET) images to predict clinical outcomes in locally advanced non-small cell lung cancer (NSCLC).

Methods

A total of 1404 primary tumour radiomic features were extracted from pre-treatment [18F]fluorodeoxyglucose (FDG)-PET scans of stage IIIA/N2 or IIIB NSCLC patients using a training cohort (n = 79; prospective Swiss multi-centre randomized phase III trial SAKK 16/00; 16 centres) and an internal validation cohort (n = 31; single centre). Robustness studies investigating delineation variation, attenuation correction and motion were performed (intraclass correlation coefficient threshold > 0.9). Two 12-/24-month event-free survival (EFS) and overall survival (OS) logistic regression models were trained using standardized imaging: (1) with robust features alone and (2) with all available features. Models were then validated using fivefold cross-validation, and validation on a separate single-centre dataset. Model performance was assessed using area under the receiver operating characteristic curve (AUC).

Results

Robustness studies identified 179 stable features (13%), with 25% stable features for 3D versus 4D acquisition, 31% for attenuation correction and 78% for delineation. Univariable analysis found no significant robust features predicting 12-/24-month EFS and 12-month OS (p value > 0.076). Prognostic models without robust preselection performed well for 12-month EFS in training (AUC = 0.73) and validation (AUC = 0.74). Patient stratification into two risk groups based on 12-month EFS was significant for training (p value = 0.02) and validation cohorts (p value = 0.03).

Conclusions

A PET-based radiomics model using a standardized, multi-centre dataset to predict EFS in locally advanced NSCLC was successfully established and validated with good performance. Prediction models with robust feature preselection were unsuccessful, indicating the need for a standardized imaging protocol.
PSMA-ligand uptake can serve as a novel biomarker in primary prostate cancer to predict outcome after radical prostatectomy
Authors: Wang Hui , Amiel Thomas , Würnschimmel Christoph , Langbein Thomas , Steiger Katja , Rauscher Isabel , Horn Thomas , Maurer Tobias , Weber Wolfgang , Wester Hans-Juergen , Knorr Karina , Eiber Matthias
Published: August 2021

Background

The prostate-specific membrane antigen (PSMA) is a relevant target in prostate cancer, and immunohistochemistry studies showed associations with outcome. PSMA-ligand positron emission tomography (PET) is increasingly used for primary prostate cancer staging, and the molecular imaging TNM classification (miTNM) standardizes its reporting. We aimed to investigate the potential of PET-imaging to serve as a noninvasive imaging biomarker to predict disease outcome in primary prostate cancer after radical prostatectomy (RP).

Methods

In this retrospective analysis, 186 primary prostate cancer patients treated with RP who had undergone a 68Ga-PSMA-11 PET up to three months prior to the surgery were included. Maximum standardized uptake value (SUVmax), SUVmean, tumor volume (TV) and total lesion (TL) were collected from PET-imaging. Moreover, clinicopathological information, including age, serum prostate-specific antigen (PSA) level, and pathological characteristics, was assessed for disease outcome prediction. A stage group system for PET-imaging findings based on the miTNM framework was developed.

Results

At a median follow-up after RP of 38 months (interquartile range (IQR) 22–53), biochemical recurrence (BCR) was observed in 58 patients during the follow-up period. A significant association between a positive surgical margin and miN status (miN1 vs. miN0, odds ratio (OR): 5.428, p = 0.004) was detected. miT status (miT ≥ 3a vs. miT < 3, OR: 2.696, p = 0.003) was identified as an independent predictor for Gleason score (GS) ≥ 8. Multivariate Cox regression analysis indicated that PSA level (hazard ratio (HR): 1.024, p = 0.014), advanced GS (GS ≥ 8 vs. GS < 8, HR: 3.253, p < 0.001) and miT status (miT ≥ 3a vs. miT < 3, HR: 1.941, p = 0.035) were independent predictors for BCR. For stage I disease as determined by PET-imaging, a shorter BCR-free survival was observed in the patients with higher SUVmax (IA vs. IB stage, log-rank, p = 0.022).

Conclusion

Preoperative miTNM classification from 68Ga-PSMA-11 PET correlates with postoperative GS, surgical margin status and time to BCR. The association between miTNM staging and outcome proposes 68Ga-PSMA-11 PET as a novel non-invasive imaging biomarker and potentially serves for ancillary pre-treatment stratification.
Investigation of spleen CXCR4 expression by [68Ga]Pentixafor PET in a cohort of 145 solid cancer patients
Authors: Lewis Richard , Habringer Stefan , Kircher Malte , Hefter Maike , Peuker Caroline Anna , Werner Rudolf , Ademaj-Kospiri Valëza , Gäble Alexander , Weber Wolfgang , Wester Hans-Jürgen , Buck Andreas , Herhaus Peter , Lapa Constantin , Keller Ulrich
Published: August 2021

Background

The chemokine receptor CXCR4 is frequently overexpressed and associated with adverse prognosis in most hematopoietic malignancies and solid cancers. Recently, CXCR4 molecular imaging using the CXCR4-specific positron emission tomography (PET) tracer Pentixafor ([68Ga]Pentixafor) has become a well-established method to non-invasively measure CXCR4 expression in vivo. In previous Pentixafor imaging studies, highly variable CXCR4 tracer uptake to the spleen was observed.

Results

We investigated the hypothesis that enhanced spleen [68Ga]Pentixafor uptake and thus CXCR4 expression in patients with solid tumors would indicate an activated spleen state and/or an association with clinical and prognostic features and survival parameters. In this retrospective study, [68Ga]Pentixafor-PET images and patient records of 145 solid tumor patients representing 27 cancer entities were investigated for an association of spleen [68Ga]Pentixafor uptake and clinical characteristics and outcome. Based on this assessment, we did not observe differences in clinical outcomes, measured by progression-free survival, overall survival and remission status neither within the entire cohort nor within subgroups of adrenal cancer, desmoplastic small round cell tumor, neuroendocrine tumors, non-small cell lung cancer, small cell lung cancer and pancreatic adenocarcinoma patients. No tumor entity showed especially high levels of spleen [68Ga]Pentixafor uptake compared to others or a control cohort. However, when investigating laboratory parameters, there was a positive correlation of high spleen [68Ga]Pentixafor uptake with leukocyte and/or platelet counts in neuroendocrine tumors, non-small cell lung cancer and small cell lung cancer.

Conclusion

Spleen [68Ga]Pentixafor uptake was not associated with stage of disease and clinical outcomes in solid tumor patients. We identified positively associated platelet and/or leukocyte counts with spleen [68Ga]Pentixafor uptake in neuroendocrine tumors, non-small cell lung cancer and small cell lung cancer, suggesting that splenic CXCR4 expression could possibly play a role in systemic immunity/inflammation in some types of solid tumors or a subgroup of patients within solid tumor entities.
[18F]FDG-PET/CT in prone compared to supine position for optimal axillary staging and treatment in clinically node-positive breast cancer patients with neoadjuvant systemic therapy
Authors: van Loevezijn Ariane A. , Stokkel Marcel P. M. , Donswijk Maarten L. , van Werkhoven Erik D. , van der Noordaa Marieke E. M. , van Duijnhoven Frederieke H. , Vrancken Peeters Marie-Jeanne T. F. D.
Published: August 2021

Purpose

Axillary staging before neoadjuvant systemic therapy in clinically node-positive breast cancer patients with tailored axillary treatment according to the Marking Axillary lymph nodes with radioactive iodine seeds (MARI)-protocol, a protocol developed at the Netherlands Cancer Institute, is performed with [18F] fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT). We aimed to assess the value of FDG-PET/CT in prone compared to standard supine position for axillary staging.

Methods

We selected patients with FDG-PET/CT in supine and prone position who underwent the MARI-protocol. One hour after administration of 3.5 MBq/kg, [18F]FDG-PET was performed with a low-dose prone position CT-thorax followed by a supine whole-body scan. Scans were separately reviewed by two nuclear medicine physicians and categorized by number of FDG-positive axillary lymph nodes (ALNs; cALN<4 or cALN≥4). Main outcome was axillary up- or downstaging.

Results

Of 153 patients included, 24 (16%) patients were up- or downstaged at evaluation of prone images: One observer upstaged 14 patients, downstaged 3  patients and reported a higher number of ALNs (3.6 vs. 3.2, p < 0.001), while staging (4 up- and 5 downstaged) and number of ALNs (2.8 vs. 2.8) did not differ for the other. Observers agreed on up- or downstaging in only 1 (1%) patient. Irrespective of supine or prone position scanning, observers agreed on axillary staging in 124 (81%) patients and disagreed in 5 (3%). Interobserver agreement was lower with prone assessments (86%, K = 0.67) than supine (92%, K = 0.80).

Conclusions

Axillary staging with FDG-PET/CT in prone compared to supine position did not result in concordant up- or downstaging. Therefore, FDG-PET/CT in supine position only can be considered sufficient for axillary staging.
On some new midpoint inequalities for the functions of two variables via quantum calculus
Authors: You Xuexiao , Ali Muhammad Aamir , Erden Samet , Budak Hüseyin , Chu Yu-Ming
Published: August 2021

In this paper, first we obtain a new identity for quantum integrals, the result is then used to prove midpoint type inequalities for differentiable coordinated convex mappings. The outcomes provided in this article are an extension of the comparable consequences in the literature on the midpoint inequalities for differentiable coordinated convex mappings.
Modeling, analysis and numerical solution to malaria fractional model with temporary immunity and relapse
Authors: ul Rehman Attiq , Singh Ram , Abdeljawad Thabet , Okyere Eric , Guran Liliana
Published: August 2021

The present paper deals with a fractional-order mathematical epidemic model of malaria transmission accompanied by temporary immunity and relapse. The model is revised by using Caputo fractional operator for the index of memory. We also recommend the utilization of temporary immunity and the possibility of relapse. The theory of locally bounded and Lipschitz is employed to inspect the existence and uniqueness of the solution of the malaria model. It is shown that temporary immunity has a great effect on the dynamical transmission of host and vector populations. The stability analysis of these equilibrium points for fractional-order derivative α and basic reproduction number $\mathcal{R}_{0}$

R
0

is discussed. The model will exhibit a Hopf-type bifurcation. The two control variables are introduced in this model to decrease the number of populations. Mandatory conditions for the control problem are produced. Two types of numerical method via Laplace Adomian decomposition and Runge–Kutta of fourth order for simulating the proposed model with fractional-order derivative are presented. To validate the mathematical results, numerical simulations, sensitivity analysis, convergence analysis, and other important studies are given. The paper is finished with some conclusions and discussion.
Refinements of some fractional integral inequalities for refined $(\alpha ,h-m)$-convex function
Authors: Jung Chahn Yong , Farid Ghulam , Yasmeen Hafsa , Lv Yu-Pei , Pečarić Josip
Published: August 2021

This article investigates new inequalities for generalized Riemann–Liouville fractional integrals via the refined $(\alpha ,h-m)$
(
α
,
h
−
m
)
-convex function. The established results give refinements of fractional integral inequalities for $(h-m)$
(
h
−
m
)
-convex, $(\alpha ,m)$
(
α
,
m
)
-convex, $(s,m)$
(
s
,
m
)
-convex, and related functions. Also, the k-fractional versions of given inequalities by using a parameter substitution are provided.
Severity: a QoS-aware approach to cloud application elasticity
Authors: Tsagkaropoulos Andreas , Verginadis Yiannis , Papageorgiou Nikos , Paraskevopoulos Fotis , Apostolou Dimitris , Mentzas Gregoris
Published: August 2021

While a multitude of cloud vendors exist today offering flexible application hosting services, the application adaptation capabilities provided in terms of autoscaling are rather limited. In most cases, a static adaptation action is used having a fixed scaling response. In the cases that a dynamic adaptation action is provided, this is based on a single scaling variable. We propose Severity, a novel algorithmic approach aiding the adaptation of cloud applications. Based on the input of the DevOps, our approach detects situations, calculates their Severity and proposes adaptations which can lead to better application performance. Severity can be calculated for any number of application QoS attributes and any type of such attributes, whether bounded or unbounded. Evaluation with four distinct workload types and a variety of monitoring attributes shows that QoS for particular application categories is improved. The feasibility of our approach is demonstrated with a prototype implementation of an application adaptation manager, for which the source code is provided.
Breast self-examination practice among women in Africa: a systematic review and Meta-analysis
Authors: Seifu Wubareg , Mekonen Liyew
Published: August 2021

Background

In resource limited countries breast self-examination has been recommended as the most appropriate method for early detection of breast cancer. Available studies conducted on breast self-examination practice in Africa currently are inconsistent and inclusive evidences. On top of that the available studies are unrepresentative by regions with small sample size. Therefore, this systematic review and meta-analysis were conducted to summarize and pool the results of individual studies to produce content level estimates of breast self-examination practice in Africa.

Methods

A systematic review and meta-analysis were done among studies conducted in Africa using Preferred Item for Systematic Review and Meta-analysis (PRISRMA) guideline. Studies were identified from PubMed, Google Scholar, HINARI, EMBASE, CINAHL, Cochrane, African Journals Online and reference lists of identified prevalence studies. Unpublished sources were also searched to retrieve relevant articles. Critical appraisal of studies was done through Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI). The meta-analysis was conducted using STATA 13 software. Heterogeneity was assessed using I2statistics while publication was assessed through funnel plot. Forest plot were used to present the pooled prevalence with a 95% confidence interval (CI) using the random effect model.

Results

In this meta-analysis 56 studies were included with a total of 19, 228 study participants. From the included studies 25(44.64%) were from West Africa, 22(39.29%) East Africa, 5(8.93%) North Africa, 3(5.36%) Central Africa and 1(1.79%) South Africa. The overall pooled prevalence of ever and regular breast self-examination practice in Africa was found to be 44.0% (95% CI: 36.63, 51.50) and 17.9% (95% CI: 13.36, 22.94) respectively. In the subgroup analysis there was significant variations between sub regions with the highest practice in West Africa, 58.87% (95 CI%: 48.06, 69.27) and the lowest in South Africa, 5.33% (95 CI%: 2.73, 10.17).

Conclusion

This systematic review and meta-analysis revealed that breast self-examination practice among women in Africa was low. Therefore, intensive behavioral change communication and interventions that emphasize different domains should be given by stakeholders.

PROSPERO registration number

CRD42020119373.
Prevotella copri increases fat accumulation in pigs fed with formula diets
Authors: Chen Congying , Fang Shaoming , Wei Hong , He Maozhang , Fu Hao , Xiong Xinwei , Zhou Yunyan , Wu Jinyuan , Gao Jun , Yang Hui , Huang Lusheng
Published: August 2021

Background

Excessive fat accumulation of pigs is undesirable, as it severely affects economic returns in the modern pig industry. Studies in humans and mice have examined the role of the gut microbiome in host energy metabolism. Commercial Duroc pigs are often fed formula diets with high energy and protein contents. Whether and how the gut microbiome under this type of diet regulates swine fat accumulation is largely unknown.

Results

In the present study, we systematically investigated the correlation of gut microbiome with pig lean meat percentage (LMP) in 698 commercial Duroc pigs and found that Prevotella copri was significantly associated with fat accumulation of pigs. Fat pigs had significantly higher abundance of P. copri in the gut. High abundance of P. copri was correlated with increased concentrations of serum metabolites associated with obesity, e.g., lipopolysaccharides, branched chain amino acids, aromatic amino acids, and the metabolites of arachidonic acid. Host intestinal barrier permeability and chronic inflammation response were increased. A gavage experiment using germ-free mice confirmed that the P. copri isolated from experimental pigs was a causal species increasing host fat accumulation and altering serum metabolites. Colon, adipose tissue, and muscle transcriptomes in P. copri-gavaged mice indicated that P. copri colonization activated host chronic inflammatory responses through the TLR4 and mTOR signaling pathways and significantly upregulated the expression of the genes related to lipogenesis and fat accumulation, but attenuated the genes associated with lipolysis, lipid transport, and muscle growth.

Conclusions

Taken together, the results proposed that P. copri in the gut microbial communities of pigs fed with commercial formula diets activates host chronic inflammatory responses by the metabolites through the TLR4 and mTOR signaling pathways, and increases host fat deposition significantly. The results provide fundamental knowledge for reducing fat accumulation in pigs through regulating the gut microbial composition.
Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein
Authors: Liu Jiluo , Chen Xi , Liu Yan , Lin Jiansheng , Shen Jiaying , Zhang Hongwei , Yin Jianhua , Pu Rui , Ding Yibo , Cao Guangwen
Published: August 2021

Background

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is pandemic. However, the origins and global transmission pattern of SARS-CoV-2 remain largely unknown. We aimed to characterize the origination and transmission of SARS-CoV-2 based on evolutionary dynamics.

Methods

Using the full-length sequences of SARS-CoV-2 with intact geographic, demographic, and temporal information worldwide from the GISAID database during 26 December 2019 and 30 November 2020, we constructed the transmission tree to depict the evolutionary process by the R package “outbreaker”. The affinity of the mutated receptor-binding region of the spike protein to angiotensin-converting enzyme 2 (ACE2) was predicted using mCSM-PPI2 software. Viral infectivity and antigenicity were tested in ACE2-transfected HEK293T cells by pseudovirus transfection and neutralizing antibody test.

Results

From 26 December 2019 to 8 March 2020, early stage of the COVID-19 pandemic, SARS-CoV-2 strains identified worldwide were mainly composed of three clusters: the Europe-based cluster including two USA-based sub-clusters; the Asia-based cluster including isolates in China, Japan, the USA, Singapore, Australia, Malaysia, and Italy; and the USA-based cluster. The SARS-CoV-2 strains identified in the USA formed four independent clades while those identified in China formed one clade. After 8 March 2020, the clusters of SARS-CoV-2 strains tended to be independent and became “pure” in each of the major countries. Twenty-two of 60 mutations in the receptor-binding domain of the spike protein were predicted to increase the binding affinity of SARS-CoV-2 to ACE2. Of all predicted mutants, the number of E484K was the largest one with 86 585 sequences, followed by S477N with 55 442 sequences worldwide. In more than ten countries, the frequencies of the isolates with E484K and S477N increased significantly. V367F and N354D mutations increased the infectivity of SARS-CoV-2 pseudoviruses (P < 0.001). SARS-CoV-2 with V367F was more sensitive to the S1-targeting neutralizing antibody than the wild-type counterpart (P < 0.001).

Conclusions

SARS-CoV-2 strains might have originated in several countries simultaneously under certain evolutionary pressure. Travel restrictions might cause location-specific SARS-CoV-2 clustering. The SARS-CoV-2 evolution appears to facilitate its transmission via altering the affinity to ACE2 or immune evasion.

Graphic Abstract