bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing the spatial distribution of multiple malaria diagnostic endpoints in a low-transmission setting in Lao PDR
Authors: Byrne Isabel , Cramer Estee , Nelli Luca , Rerolle Francois , Wu Lindsey , Patterson Catriona , Rosado Jason , Dumont Elin , Tetteh Kevin K. A. , Dantzer Emily , Hongvanthong Bouasy , Fornace Kimberley M. , Stresman Gillian , Lover Andrew , Bennett Adam , Drakeley Chris
Published: August 2022

The epidemiology of malaria changes as prevalence falls in low-transmission settings, with remaining infections becoming more difficult to detect and diagnose. At this stage active surveillance is critical to detect residual hotspots of transmission. However, diagnostic tools used in active surveillance generally only detect concurrent infections, and surveys may benefit from sensitive tools such as serological assays. Serology can be used to interrogate and characterize individuals' previous exposure to malaria over longer durations, providing information essential to the detection of remaining foci of infection. We ran blood samples collected from a 2016 population-based survey in the low-transmission setting of northern Lao PDR on a multiplexed bead assay to characterize historic and recent exposures to Plasmodium falciparum and vivax. Using geostatistical methods and remote-sensing data we assessed the environmental and spatial associations with exposure, and created predictive maps of exposure within the study sites. We additionally linked the active surveillance PCR and serology data with passively collected surveillance data from health facility records. We aimed to highlight the added information which can be gained from serology as a tool in active surveillance surveys in low-transmission settings, and to identify priority areas for national surveillance programmes where malaria risk is higher. We also discuss the issues faced when linking malaria data from multiple sources using multiple diagnostic endpoints.
Adding predictive and diagnostic values of pulmonary ground-glass nodules on lung cancer via novel non-invasive tests
Authors: Ding Yizong , He Chunming , Zhao Xiaojing , Xue Song , Tang Jian
Published: August 2022

Pulmonary ground-glass nodules (GGNs) are highly associated with lung cancer. Extensive studies using thin-section high-resolution CT images have been conducted to analyze characteristics of different types of GGNs in order to evaluate and determine the predictive and diagnostic values of GGNs on lung cancer. Accurate prediction of their malignancy and invasiveness is critical for developing individualized therapies and follow-up strategies for a better clinical outcome. Through reviewing the recent 5-year research on the association between pulmonary GGNs and lung cancer, we focused on the radiologic and pathological characteristics of different types of GGNs, pointed out the risk factors associated with malignancy, discussed recent genetic analysis and biomarker studies (including autoantibodies, cell-free miRNAs, cell-free DNA, and DNA methylation) for developing novel diagnostic tools. Based on current progress in this research area, we summarized a process from screening, diagnosis to follow-up of GGNs.
Characterizing pharmacogenetic programs using the consolidated framework for implementation research: A structured scoping review
Authors: McDermott John H. , Wright Stuart , Sharma Videha , Newman William G. , Payne Katherine , Wilson Paul
Published: August 2022

Several healthcare organizations have developed pre-emptive pharmacogenetic testing programs, where testing is undertaken prior to the prescription of a medicine. This review characterizes the barriers and facilitators which influenced the development of these programs. A bidirectional citation searching strategy identified relevant publications before a standardized data extraction approach was applied. Publications were grouped by program and data synthesis was undertaken using the Consolidated Framework for Implementation Research (CFIR). 104 publications were identified from 40 programs and 4 multi-center initiatives. 26 (66%) of the programs were based in the United States and 95% in high-income countries. The programs were heterogeneous in their design and scale. The Characteristics of the Intervention, Inner Setting, and Process domains were referenced by 92.5, 80, and 77.5% of programs, respectively. A positive institutional culture, leadership engagement, engaging stakeholders, and the use of clinical champions were frequently described as facilitators to implementation. Clinician self-efficacy, lack of stakeholder knowledge, and the cost of the intervention were commonly cited barriers. Despite variation between the programs, there were several similarities in approach which could be categorized via the CFIR. These form a resource for organizations planning the development of pharmacogenetic programs, highlighting key facilitators which can be leveraged to promote successful implementation.
Aurantii Fructus Immaturus enhances natural killer cytolytic activity and anticancer efficacy in vitro and in vivo
Authors: Park Arum , Yang Yunjeong , Lee Yunhee , Jung Haiyoung , Kim Tae-Don , Noh Ji-Yoon , Lee Seungjin , Yoon Suk Ran
Published: August 2022

Aurantii Fructus Immaturus(AFI), extensively used in traditional herbal medicine, is known to have diverse physiological effects against various diseases, including obesity, diabetes, and cardiovascular disease. However, the effects of AFI on the immune system, especially natural killer (NK) cells, remain largely unknown. We aimed to investigate the effect of AFI on NK cell activityin vitroandin vivoand to elucidate the underlying mechanisms. Further, we verified the anticancer efficacy of AFI in a mouse lung metastasis model, underscoring the therapeutic potential of AFI in cancer therapy. Our results revealed that AFI significantly enhanced the cytolytic activity of NK cells in a dose-dependent manner, accompanied by an increase in the expression of NK cell-activating receptors, especially NKp30 and NKp46. AFI treatment also increased the expression of cytolytic granules, including granzyme B and perforin. Furthermore, the expression of CD107a, a degranulation marker, was increased upon treatment with AFI. A signaling study using western blot analysis demonstrated that the phosphorylation of extracellular signal-regulated kinase (ERK) was involved in increasing the NK cell activity following AFI treatment. In thein vivostudy performed in mice, oral administration of AFI markedly enhanced the cytotoxic activity of spleen mononuclear cells against YAC-1 cells, which was accompanied by NKp46 upregulation. In addition, we confirmed that cancer metastasis was inhibited in a mouse cancer metastasis model, established using the mouse melanoma B16F10 cell line, by the administration of AFIin vivo.Collectively, these results indicate that AFI enhances NK cell-mediated cytotoxicityin vitroandin vivo viaactivation of the ERK signaling pathway and suggest that AFI could be a potential supplement for cancer immunotherapy.
ISupport-Brasil: Preliminary results of the usability and acceptability assessment by caregivers of people who have dementia
Authors: Ottaviani Ana Carolina , Monteiro Diana Quirino , Ferreira Campos Camila Rafael , Barham Elizabeth Joan , Oliveira Déborah , da Cruz Keila Cristianne Trindade , Corrêa Larissa , de Souza Orlandi Fabiana , Zazzetta Marisa Silvana , Gratão Aline Cristina Martins , Pavarini Sofia Cristina Iost
Published: August 2022

Objective

To assess usability and acceptability of iSupport-Brasil (iSupport-BR) to virtually support family caregivers of people who have dementia.

Materials and methods

In the first stage, nine caregivers/former caregivers assessed the interface of the platform that hosts iSupport-BR. In the second stage, 10 caregivers assessed acceptability of the platform and answered the System Usability Scale (SUS), which varies from 0 to 100 points. A descriptive analysis of the quantitative data was performed, as well as a thematic analysis on the open questions. All the ethical aspects were respected.

Results

The results of the first stage indicated a user-friendly interface of the system and relevant content of the program, with 55.6 and 77.8% of the participants assigning the maximum grade to these questions, respectively. Of the five possible points, the system’s mean score was 3.7. In Stage 2, 80% of the caregivers rated the program as very useful and 100% would recommend it to other caregivers. Perception of the program’s usability by the SUS scale was excellent (M = 86.5 ± 11.5).

Conclusion

This research allowed elaborating the final version of iSupport-BR, considering usability and acceptability of the platform and the program for computers/notebooks, being a pioneer in evaluating it for use in smartphones. Future research studies will have to assess the effects of iSupport-BR on the caregivers’ mental health.
Continuous glucose monitoring as a close to real life alternative to meal studies – a pilot study with a functional drink containing amino acids and chromium
Authors: Samigullin Azat , Humpert Per M. , Östman Elin
Published: August 2022

This pilot study aimed to evaluate a continuous glucose monitoring (CGM) based approach to study the effects of a functional drink containing specific amino acids and chromium picolinate (FD) and a combination of FD with a juice (FDJ) on postprandial glucose in a close to real life setting. The predefined primary endpoint for this study was the 120-min incremental area under the glucose curve (iAUC0−120min) after meals. It was estimated that using CGM and repeated meals in 6 participants could be sufficient to match the power of the previous study in regards to the quantity of meals. Participants followed a pre-specified meal schedule over 9 days and consumed the drinks three times daily with main meals. Differences between drinks were analyzed by analysis of covariances (ANCOVA) with subject number and activity as random factors and nutrient composition as covariates. In 156 meals available for analysis, a significant 34% reduction of glucose iAUC0−120min was shown for FDJ (p < 0.001). FD did not show a significant effect on its own, but a significant reduction of 17.6% (p = 0.007) was shown in pooled data for FD and FDJ. While the differences between the two functional drinks used were not the primary focus of this study, it was sufficiently powered to detect previously described effects in 60 participants in a cross-over design under laboratory settings. The design presented defines a novel and cost-effective approach using CGM devices and app-based lifestyle tracking for studying nutritional effects on glucose at home in a close to real-life setting.
Neonatal Streptococcus pneumoniae infection induces long-lasting dysbiosis of the gut microbiota in a mouse model
Authors: Li Yuanyuan , Xu Ximing , Guo Ziyao , Li Qinyuan , Wang Yiying , Jian Ding , Zhang Guangli , Tian Xiaoyin , Chen Shiyi , Luo Zhengxiu
Published: August 2022

Early life is a “critical window” for gut microbiota development, antibiotic use during this period exerts a profound effect on gut microbial dysbiosis and asthma. In clinical practice, antibiotics are usually used in patients with bacterial infections, we previously showed that neonatal S. pneumoniae pneumonia promoted adult-onset asthma in mice model, while it remains unclear whether neonatal S. pneumoniae infection have long-term effects on gut microbiota. Neonatal BALB/c mice were inoculated with 5*106 CFU D39 to establish non-lethal S. pneumoniae pneumonia model. At 2, 3, 8 weeks of age, feces in the cecum were prepared for 16S rRNA sequencing, lungs were collected for histopathologic and lung function analysis. S. pneumoniae-infected neonatal mice exhibited histopathologic lesions in their lungs and increased airway hyperresponsiveness, obvious alterations in alpha and beta diversities in the entire gut microbiota, and changes of the community structure during the breastfeeding period, infancy, and adulthood. Furthermore, gut microbial composition was modified after neonatal S. pneumoniae infection, with a decreased relative abundance of Lactobacillus in the breastfeeding period and infancy; in adulthood, the relative abundance of Allobaculum diminished while that of Proteobacteria was augmented. Neonatal S. pneumoniae infection induced a long-term alteration in microbial community composition.
Hormetic effect of 17α-ethynylestradiol on activated sludge microbial community response
Authors: Budeli Phumudzo , Ekwanzala Mutshiene Deogratias , Momba Maggy Ndombo Benteke
Published: August 2022

Synthetic estrogen analogues are among the most potent estrogenic contaminants in effluents from wastewater treatment plants. Although its effects have been well elucidated in the feminization of male fish and interference with the endocrine systems in humans, it has not been fully explored in the activated sludge (AS) microbiome, particularly EE2 (17α-ethynylestradiol). Therefore, in this study, the bacterial community shift in a 6-day laboratory-scale reactor in environmental (0, 5, 10, and 100 ng/L) and predictive elevated concentrations (5, 10, and 100 mg/L) of EE2 was investigated using culture-based and metagenomics approaches. Results showed significant changes (t-test, all p < 0.05) between initial and final physicochemical parameters (pH, DO, and EC). Although environmental concentrations showed a slight decrease in microbial counts (5.6 × 106 to 4.6 × 106 CFU/ml) after a 24-h incubation for the culturable approach, the predictive elevated concentrations (5 to 100 mg/L) revealed a drastic microbial counts reduction (5.6 × 106 to 8 × 102 CFU/ml). The metagenomic data analysis uncovered that bacterial communities in the control sample were dominated by Proteobacteria, followed by Bacteroidetes and Firmicutes. The taxonomic classification after exposure of microbial communities in various concentrations revealed significant differences in community composition between environmental concentration (Shannon indices between 2.58 to 3.68) and predictive elevated concentrations (Shannon indices between 2.24 and 2.84; t-test, all p < 0.05). The EE2 enriched seven OTUs were Novosphingobium, Cloacibacterium, Stenotrophomonas, Enterobacteriaceae_unclassified, Stenotrophomonas, Enterobacteriaceae_unclassified and Rhodobacteraceae_unclassified. These results were supported by a dehydrogenase activity (DHA) test, which demonstrated less (about 40%) DHA in predictive elevated concentrations than in environmental concentrations. Notwithstanding, these findings suggest that EE2 may possess potent hormetic effect as evidenced by promotion of microbiome richness and dehydrogenase activity of AS in lower EE2 doses.
Genetic network analysis of human immunodeficiency virus sexual transmission in rural Southwest China after the expansion of antiretroviral therapy: A population-based study
Authors: Chen Jin , Chen Huanhuan , Li Jianjun , Luo Liuhong , Kang Ruihua , Liang Shujia , Zhu Qiuying , Lu Huaxiang , Zhu Jinhui , Shen Zhiyong , Feng Yi , Liao Lingjie , Xing Hui , Shao Yiming , Ruan Yuhua , Lan Guanghua
Published: August 2022

Background

This study is used to analyze the genetic network of HIV sexual transmission in rural areas of Southwest China after expanding antiretroviral therapy (ART) and to investigate the factors associated with HIV sexual transmission through the genetic network.

Materials and methods

This was a longitudinal genetic network study in Guangxi, China. The baseline survey and follow-up study were conducted among patients with HIV in 2015, and among those newly diagnosed from 2016 to 2018, respectively. A generalized estimating equation model was employed to explore the factors associated with HIV transmission through the genetic linkage between newly diagnosed patients with HIV (2016–2018) and those at baseline (2015–2017), respectively.

Results

Of 3,259 identified HIV patient sequences, 2,714 patients were at baseline, and 545 were newly diagnosed patients with HIV at follow-up. A total of 8,691 baseline objectives were observed by repeated measurement analysis. The prevention efficacy in HIV transmission for treated HIV patients was 33% [adjusted odds ratio (AOR): 0.67, 95% confidence interval (CI): 0.48–0.93]. Stratified analyses indicated the prevention efficacy in HIV transmission for treated HIV patients with a viral load (VL) of <50 copies/ml and those treated for 4 years with a VL of <50 copies/ml to be 41 [AOR: 0.59, 95% CI: 0.43–0.82] and 65% [AOR: 0.35, 95% CI: 0.24–0.50], respectively. No significant reduction in HIV transmission occurred among treated HIV patients with VL missing or treated HIV patients on dropout. Some factors were associated with HIV transmission, including over 50 years old, men, Zhuang and other nationalities, with less than secondary schooling, working as a farmer, and heterosexual transmission.

Conclusion

This study reveals the role of ART in reducing HIV transmission, and those older male farmers with less than secondary schooling are at high risk of HIV infection at a population level. Improvements to ART efficacy for patients with HIV and precision intervention on high-risk individuals during the expansion of ART are urgently required.
The prion-like transmission of tau oligomers via exosomes
Authors: Jackson Noel A. , Guerrero-Muñoz Marcos J. , Castillo-Carranza Diana L.
Published: August 2022

The conversion and transmission of misfolded proteins established the basis for the prion concept. Neurodegenerative diseases are considered “prion-like” disorders that lack infectivity. Among them, tauopathies are characterized by the conversion of native tau protein into an abnormally folded aggregate. During the progression of the disease, misfolded tau polymerizes into oligomers and intracellular neurofibrillary tangles (NFTs). While the toxicity of NFTs is an ongoing debate, the contribution of tau oligomers to early onset neurodegenerative pathogenesis is accepted. Tau oligomers are readily transferred from neuron to neuron propagating through the brain inducing neurodegeneration. Recently, transmission of tau oligomers via exosomes is now proposed. There is still too much to uncover about tau misfolding and propagation. Here we summarize novel findings of tau oligomers transmission and propagation via exosomes.
Characterizing Plasma Biomarkers of Alzheimer's in a Diverse Community-Based Cohort: A Cross-Sectional Study of the HAB-HD Cohort
Authors: Hall James R. , Petersen Melissa , Johnson Leigh , O'Bryant Sid E.
Published: August 2022

Background

Due to their low cost, less invasive nature, and ready availability, plasma biomarkers of Alzheimer's disease have been proposed as one-time screening tools for clinical trials and research. The impact of ethnoracial factors on these biomarkers has received little attention. The current cross-sectional study investigated the levels of Aβ40, Aβ42, total tau (t tau), and neurofilament light (NfL) across diagnoses for each of the three major ethnoracial groups in the United States in a community-based cohort of older adults.

Methods

A total of 1,862 participants (852 Mexican Americans (MAs); 775 non-Hispanic Whites (NHWs), and 235 African Americans (AAs)) drawn from The Health & Aging Brain Study—Health Disparities (HABS-HD) study were included. Diagnoses were assigned using an algorithm (decision tree) verified by consensus review. Plasma samples were assayed using Simoa technology. Levels of each biomarker were compared for the three ethnoracial groups across cognitive diagnoses using ANOVA covarying sex and age.

Results

Significant differences were found across the groups at each level of cognitive impairment. Cognitively unimpaired (CU) AA had significantly lower levels of each of the biomarkers than cognitively unimpaired MA or NHW and NHW had higher levels of Aβ40, and NfL than the other two groups. MA had higher t tau than AA or NHW. Mild cognitive impairment (MCI) group NHW had the highest levels on all the biomarkers and AA had the lowest. NHW and MA have higher levels of Aβ40, Aβ42, and t tau there was no difference between the groups for Aβ42. NHW had significantly higher levels of Aβ40, t tau, and NfL than AA. AA had a higher Aβ42/Aβ40 ratio than either NHW or MA for CU MCI.

Conclusions

The use of plasma biomarkers of cognitive decline is promising given their advantages over other biomarkers such as CSF and imaging but as the current research shows, ethnoracial differences must be considered to enhance accuracy and utility. Developing ethnoracial-specific cut points and establishing normative ranges by assay platform for each of the biomarkers are needed. Longitudinal research to assess changes in biomarkers during a cognitive decline is ongoing.
Thrombin generation as a predictor of outcomes in patients with non-traumatic intracerebral hemorrhage
Authors: Lóczi Linda , Orbán-Kálmándi Rita , Árokszállási Tamás , Fekete István , Fekete Klára , Héja Máté , Tóth Judit , Csiba László , Bagoly Zsuzsa
Published: August 2022

Background

Non-traumatic intracerebral hemorrhage (ICH) accounts for 10–15% of all strokes and leads to a higher rate of mortality as compared to ischemic strokes. We aimed to find out whether the thrombin generation assay (TGA) could predict outcomes in patients with ICH.

Patients and methods

In this prospective, observational study, 87 consecutive patients with ICH and 164 healthy controls were included. Computed tomography (CT), detailed clinical investigation, and laboratory investigations were performed from patients on admission. TGA was performed using stored platelet poor plasma obtained on admission. Lag time, endogen thrombin potential (ETP), peak thrombin, and time to peak parameters were calculated. Short- and long-term outcomes of ICH were defined at 14 days and 3 months post-event according to the NIHSS and the modified Rankin Scale (mRS), respectively.

Results

Peak thrombin was significantly higher in patients as compared to controls (397.2 ± 93.9 vs. 306 ± 85.3 nM, p < 0.0001). Lag time, ETP, and time to peak parameters showed a significant positive correlation with CRP in both groups. In patients with worse long-term functional outcomes, peak thrombin was significantly higher as compared to those with favorable outcomes [mRS 2–6 median: 402.5 (IQR:344.8–473.8) vs. mRS 0–1: 326.4 (294.2–416.1) nM, p = 0.0096]. Based on the statistically optimal threshold of 339.1 nM peak thrombin, the sensitivity and specificity of this parameter to determine mRS 2–6 as an outcome were 80.8 and 64.7%, respectively. In a binary logistic regression model including age, sex, BMI, smoking status, NIHSS on admission, D-dimer, and peak thrombin (>339.1 nM), only NIHSS and the peak thrombin parameters remained in the model as significant, independent predictors of poor outcome. Lag time and time to peak showed a modest, significant negative correlation with intracerebral bleeding volume on admission (r = −0.2603, p = 0.0231 and r = −0.3698, p = 0.0010, respectively). During the follow-up of patients, estimated hemorrhage volumes on day 90 showed significant positive association with the ETP and peak thrombin parameters (r = 0.3838, p = 0.0363 and r = 0.5383, p = 0.0021, respectively).

Conclusion

In patients with ICH, TG was increased as compared to healthy controls, which might be explained by the presence of higher inflammatory parameters in patients. Peak thrombin measured on admission might be a useful tool to predict outcomes in patients with ICH.
Evaluating the relationship between right-to-left shunt and white matter hyperintensities in migraine patients: A systematic review and meta-analysis
Authors: Yeo Joshua Y. P. , Goh Claire X. Y. , Tan Ying Kiat , Sim Bryan T. S. , Chan Beverly L. X. , Syn Nicholas L. , Lim Yinghao , Chan Amanda C. Y. , Sharma Vijay K. , Ong Jonathan J. Y. , Yeo Leonard L. L. , Sia Ching-Hui , Tan Benjamin Y. Q.
Published: August 2022

Introduction

White matter hyperintensities (WMHs) have been observed with greater frequency in patients with migraine and are thought to be associated with impaired cognition and function. The relationship between WMHs and right-to-left shunt (RLS) in migraine patients is unknown. We performed a systematic review to determine if there is an association between RLS and WMHs in patients with migraine.

Methods

A systematic search of the literature was performed in PubMed and Embase using a suitable keyword search strategy from inception up to 16th June 2021. All studies that included patients with migraine and studied RLS and WMHs were included.

Results

A total of 8 non-randomized observational studies comprising 1125 patients with migraine were included; 576 had an RLS, compared to 549 patients with no RLS. The mean age of the study populations ranged from 28.4 to 43 years, while the average duration from migraine diagnosis ranged from 5.1 to 19 years. The proportion of female to male patients was consistently higher in all studies (60.0–94.4%). Amongst migraine patients with RLS, 338 patients (58.7%) had WMHs. In contrast, 256 (46.6%) of migraine patients without RLS had WMHs. RLS was significantly associated with the presence of WMHs in migraine patients (OR: 1.56, 95% CI: 1.05–2.34, p = 0.03).

Conclusion

In migraine patients, RLS was significantly associated with the presence of WMHs. Longitudinal studies are warranted to establish RLS as a risk factor for WMHs in patients with migraine, and to establish the significance of these changes.
Effects of auricular acupuncture stimulation on healthy adults’ upper limb motor-evoked potentials: A randomized, crossover, double-blind study
Authors: Zhang Jin , Huang Wen-Hao , Zheng Ya-Dan , Li Xin , Jiang Hao-Xiang , Su Min-Zhi , Huang Xiao-Yan , Dou Zu-Lin , Tang Zhi-Ming
Published: August 2022

Objective

The aim of this study was to determine whether auricular acupuncture has neuromodulatory effects on the motor cortex of healthy adults.

Methods

Fourteen healthy subjects received a real auricular acupuncture stimulation (SF1) session and a sham acupuncture stimulation session. The interval between the two types of stimulation was more than 24 h. A finger dexterity test (taping score and taping speed by using ipad) was assessed, and motor-evoked potentials (MEP) were assessed before and after each stimulation.

Results

Before the treatment, there were no significant differences in MEP amplitude, tapping score, or tapping speed (P > 0.05) between the real and sham stimulation conditions. After the treatment, the MEP amplitude, tapping score, and tapping speed in the real stimulation condition increased significantly compared to the pre-stimulation measurements and were significantly higher than those in the sham stimulation condition (P < 0.01). In the sham stimulation condition, the MEP amplitude, tapping score, and tapping speed decreased significantly compared to the pre-stimulation measurements (P < 0.05).

Conclusion

Acupuncture of auricular points can modulate the excitability of the motor cortex area of controlling the upper limbs.

Clinical trial registration

[http://www.chictr.org.cn/index.aspx], identifier [ChiCTR2100051608].
A high throughput generative vector autoregression model for stochastic synapses
Authors: Hennen Tyler , Elias Alexander , Nodin Jean-François , Molas Gabriel , Waser Rainer , Wouters Dirk J. , Bedau Daniel
Published: August 2022

By imitating the synaptic connectivity and plasticity of the brain, emerging electronic nanodevices offer new opportunities as the building blocks of neuromorphic systems. One challenge for large-scale simulations of computational architectures based on emerging devices is to accurately capture device response, hysteresis, noise, and the covariance structure in the temporal domain as well as between the different device parameters. We address this challenge with a high throughput generative model for synaptic arrays that is based on a recently available type of electrical measurement data for resistive memory cells. We map this real-world data onto a vector autoregressive stochastic process to accurately reproduce the device parameters and their cross-correlation structure. While closely matching the measured data, our model is still very fast; we provide parallelized implementations for both CPUs and GPUs and demonstrate array sizes above one billion cells and throughputs exceeding one hundred million weight updates per second, above the pixel rate of a 30 frames/s 4K video stream.
Dietary consumption of cruciferous vegetables and bladder cancer risk: A systematic review and meta-analysis
Authors: Yu Pengkui , Yu Lin , Lu Yi
Published: August 2022

Objective

Previous studies on the association of cruciferous vegetables intake with bladder cancer risk have reported inconsistent results. We performed the present meta-analysis to summarize evidence on this association and to quantify the potential dose-response relation based on all available cohort studies.

Methods

A comprehensive literature search of relevant articles up to March 2022 was performed in PubMed and EMBASE. The summary risk estimates with 95% confidence intervals for the highest vs. the lowest intake of cruciferous vegetables were calculated. Dose-response meta-analysis was also performed for studies reporting categorical risk estimates for at least three quantitative levels of cruciferous vegetables intake.

Results

We found that the highest cruciferous vegetables intake was not significantly associated with a lower risk of bladder cancer, compared with the lowest cruciferous vegetables intake category (RR = 0.92, 95% CI 0.80–1.06). Linear dose-response meta-analysis indicated that the pooled RRs for 10 g/day or 1 servings/week increment of cruciferous vegetables intake was not significantly associated with a reduced risk of bladder cancer (P = 0.106 and P = 0.147, respectively). There was no evidence of significant publication bias either with Begg’s test (P = 0.386) or Egger’s test (P = 0.253).

Conclusion

The results of this study did not support the hypothesis that dietary cruciferous vegetables intake was associated with a lower risk of bladder cancer. Further large prospective cohort studies are warranted to confirm our preliminary findings.
Plasma polyunsaturated fatty acid concentrations and sleep apnea risk: A two-sample Mendelian randomization study
Authors: Wang Jiao , Huang Yingyue , Yang Huiling , Lin Zihong , Campos Adrian I. , Rentería Miguel E. , Xu Lin
Published: August 2022

Background

Previous observational studies have found that lower levels of circulating polyunsaturated fatty acids (PUFAs) were associated with a higher risk of sleep apnea (SA). However, the causality of the association remains unclear.

Materials and methods

We used the two-sample Mendelian randomization (MR) study to assess the causal association of omega-3 and omega-6 fatty acids with SA. Single-nucleotide polymorphisms (SNPs) predicting the plasma level of PUFAs at the suggestive genome-wide significance level (p < 5 × 10–6) were selected as instrumental variables (IVs) from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) (n = ∼8,000) Consortium. For outcomes, the summary-level statistics of SA were obtained from the latest genome-wide association study (GWAS), which combined five cohorts with a total number of 25,008 SA cases and 172,050 snoring cases (total = 523,366).

Results

We found no association of α-linolenic acid (ALA) [odds ratio (OR) = 1.09 per% changed, 95% confidence interval (CI) 0.67–1.78], eicosapentaenoic acid (EPA) (OR = 0.94, 95% CI 0.88–1.01), docosapentaenoic acid (DPA) (OR = 0.95, 95% CI 0.88–1.02), and docosahexaenoic acid (DHA) (OR = 0.99, 95% CI 0.96–1.02) with the risk of SA using inverse-variance weighted (IVW) method. Moreover, for omega-6 PUFAs, no association between linoleic acid (LA) (OR = 0.98, 95% CI 0.96–1.01), arachidonic acid (AA) (1.00, 95% CI 0.99–1.01), and adrenic acid (AdrA) (0.93, 95% CI 0.71–1.21) with the risk of SA was found. Similarly, no associations of PUFAs with SA were found in single-locus MR analysis.

Conclusion

In the current study, we first found that there is no genetic evidence to support the causal role of omega-3 and omega-6 PUFAs in the risk of SA. From a public health perspective, our findings refute the notion that consumption of foods rich in PUFAs or the use of PUFAs supplementation can reduce the risk of SA.
Prediction and clinical impact of delayed lymphopenia after chemoradiotherapy in locally advanced non-small cell lung cancer
Authors: Kang Byung-Hee , Li Xue , Son Jaeman , Song Changhoon , Kang Hyun-Cheol , Kim Hak Jae , Wu Hong-Gyun , Lee Joo Ho
Published: August 2022

Introduction

The dosimetric factors of radiotherapy have an acute impact on the host immune system during chemoradiotherapy (CRT) in locally advanced non-small cell lung cancer (NSCLC). However, even after CRT, a substantial number of patients remain immunosuppressed with delayed lymphopenia. Therefore, we aimed to evaluate clinical and dose-volumetric predictors of delayed lymphopenia after CRT in locally advanced NSCLC.

Materials and methods

We retrospectively reviewed 272 patients with locally advanced NSCLC who received definitive CRT from January 2012 to August 2020. Differential blood count data, including serum albumin values, were obtained at baseline, during and at first follow up after CRT. Acute and delayed lymphopenia events were defined as grade III/IV lymphopenia developed during or 4-12 weeks after CRT completion, which accounted for 84% and 10% of cases, respectively. Dose-volume histogram parameters for planned target volume, whole body, heart, lung, great vessels, spleen, esophagus and thoracic vertebral bodies were evaluated.

Results

Multivariate analysis revealed that patients with delayed lymphopenia were associated with inferior overall survival (HR 2.53, P = 0.001) and progression-free survival (HR 1.98, P = 0.006). However, there was no significant survival difference between groups stratified by acute lymphopenia. On multivariable logistic regression models, lung V5, baseline ALC, during-CRT ALC, and albumin nadir were significant predictors for delayed lymphopenia. Furthermore, the nomogram for delayed lymphopenia based on these variables had good discrimination (area under the curve, 0.905).

Conclusions

In this study, we investigated the prognostic significance of delayed lymphopenia and identified clinico-dosimetric parameters to predict delayed lymphopenia.
The evolving role of morphology in endometrial cancer diagnostics: From histopathology and molecular testing towards integrative data analysis by deep learning
Authors: Fremond Sarah , Koelzer Viktor Hendrik , Horeweg Nanda , Bosse Tjalling
Published: August 2022

Endometrial cancer (EC) diagnostics is evolving into a system in which molecular aspects are increasingly important. The traditional histological subtype-driven classification has shifted to a molecular-based classification that stratifies EC into DNA polymerase epsilon mutated (POLEmut), mismatch repair deficient (MMRd), and p53 abnormal (p53abn), and the remaining EC as no specific molecular profile (NSMP). The molecular EC classification has been implemented in the World Health Organization 2020 classification and the 2021 European treatment guidelines, as it serves as a better basis for patient management. As a result, the integration of the molecular class with histopathological variables has become a critical focus of recent EC research. Pathologists have observed and described several morphological characteristics in association with specific genomic alterations, but these appear insufficient to accurately classify patients according to molecular subgroups. This requires pathologists to rely on molecular ancillary tests in routine workup. In this new era, it has become increasingly challenging to assign clinically relevant weights to histological and molecular features on an individual patient basis. Deep learning (DL) technology opens new options for the integrative analysis of multi-modal image and molecular datasets with clinical outcomes. Proof-of-concept studies in other cancers showed promising accuracy in predicting molecular alterations from H&E-stained tumor slide images. This suggests that some morphological characteristics that are associated with molecular alterations could be identified in EC, too, expanding the current understanding of the molecular-driven EC classification. Here in this review, we report the morphological characteristics of the molecular EC classification currently identified in the literature. Given the new challenges in EC diagnostics, this review discusses, therefore, the potential supportive role that DL could have, by providing an outlook on all relevant studies using DL on histopathology images in various cancer types with a focus on EC. Finally, we touch upon how DL might shape the management of future EC patients.
Inter-fraction heart displacement during voluntary deep inspiration breath hold radiation therapy without visual feedback measured by daily CBCT
Authors: Benkhaled Sofian , Gomes da Silveira Cauduro Carolina , Jullian Nicolas , Desmet Antoine , Rodriguez Diana , Jourani Younes , Van Gestel Dirk , De Caluwé Alex
Published: August 2022

Purpose/Objective

Deep Inspiration Breath Hold (DIBH) is now considered as the standard of care for many breast cancer patients. However, there are still uncertainties about the dose given to the heart, and it is unknown if patients may improve voluntary DIBH depth by gaining experience during treatment. In this study, we will examine the interfractional three-dimensional (3D) heart displacement throughout voluntary DIBH (vDIBH) radiotherapy by means of daily cone-beam computed tomography (CBCT).

Material and methods

Two hundred twenty-five unique CBCTs from 15 patients treated in 15 fractions were analyzed. During CBCT, a vDIBH was conducted without any visual feedback. Patients performed their DIBH freely after receiving explanations and training. After daily CBCT matching to the chest wall (CW), surface-guided radiation therapy (SGRT) tracked DIBH depth to ensure that the CW position was the same as the daily acquired CBCT. The CBCTs were retrospectively registered to the DIBH planning-CT to calculate daily changes in heart displacement relative to the CW.

Results

The mean displacement of the heart during DIBH treatment relative to the DIBH planning-CT was as follows: 1.1 mm to the right, interquartile range (IQR) 8.0; 0.5 mm superiorly, IQR 4.8; and 0 mm posteriorly, IQR 6.4. The Spearman correlation coefficients (rs) were -0.15 (p=0.025), 0.04 (p=0.549), and 0.03 (p=0.612) for the X, Y, and Z directions, respectively. The differences in median heart displacement were significant: Friedmann rank sum test p=0.031 and pairwise comparison using the Wilcoxon rank-sum test were p=0.008 for X and Y; p=0.33 for X and Z; and p=0.07 for Y and Z. The total median heart motion was δtot median= 7.26 mm, IQR= 6.86 mm.

Conclusion

During DIBH, clinicians must be aware of the wide range of intra- and inter-individual heart position variations. The inter-individual heterogeneity shown in our study should be investigated further in order to avoid unexpected cardiac overexposure and to develop a more accurate heart dose-volume model.
Degradation strategy of cyclin D1 in cancer cells and the potential clinical application
Authors: Chen Shuyi , Li Ling
Published: August 2022

Cyclin D1 has been reported to be upregulated in several solid and hematologic tumors, promoting cancer progression. Thus, decreasing cyclin D1 by degradation could be a promising target strategy for cancer therapy. This mini review summarizes the roles of cyclin D1 in tumorigenesis and progression and its degradation strategies. Besides, we proposed an exploration of the degradation of cyclin D1 by FBX4, an F box protein belonging to the E3 ligase SKP-CUL-F-box (SCF) complex, which mediates substrate ubiquitination, as well as a postulate about the concrete combination mode of FBX4 and cyclin D1. Furthermore, we proposed a possible photodynamic therapy strategythat is based on the above concrete combination mode for treating superficial cancer.
A novel glycosyltransferase-related lncRNA signature correlates with lung adenocarcinoma prognosis
Authors: Bian Chengyu , Sun Xinti , Huang Jingjing , Zhang Wenhao , Mu Guang , Wei Ke , Chen Liang , Xia Yang , Wang Jun
Published: August 2022

Background

Lung adenocarcinoma (LUAD) is one of the most fatal cancers in the world. Previous studies have shown the increase in glycosylation level, and abnormal expressions of related enzymes are closely related to various cancers. Long non-coding RNAs (lncRNAs) play an important role in the proliferation, metabolism, and migration of cancer cells, but the underlying role of glycosyltransferase (GT)-related lncRNAs in LUAD remains to be elucidated.

Methods

We abstracted 14,056 lncRNAs from The Cancer Genome Atlas (TCGA) dataset and 257 GT-related genes from the Gene Set Enrichment Analysis (GSEA) database. Univariate, LASSO-penalized, and multivariate Cox regression analyses were conducted to construct a GT-related lncRNA prognosis model.

Results

A total of 2,726 GT-related lncRNAs were identified through Pearson’s correlation analysis, and eight of them were utilized to construct a GT-related lncRNA model. The overall survival (OS) of the low-risk group continued to be superior to that of the high-risk group according to the subgroups classified by clinical features. The risk model was proved to have independent prognostic characteristics for LUAD by univariate and multivariate Cox regression analyses. The status of the tumor immune microenvironment and the relevant immunotherapy response was significantly different between the two risk groups. The candidate drugs aimed at LUAD subtype differentiation were identified.

Conclusion

We constructed a risk model comprising eight GT-related lncRNAs which was identified as an independent predictor of prognoses to predict patient survival and guide-related treatments for patients with LUAD.
Efficacy, safety, and feasibility of volumetric modulated arc therapy for synchronous bilateral breast cancer management
Authors: Quesada Stanislas , Fenoglietto Pascal , Gourgou Sophie , Lemanski Claire , Draghici Roxana , Ailleres Norbert , Prunaretty Jessica , Azria David , Bourgier Céline
Published: August 2022

Purpose

Volumetric Modulated Arc Therapy (VMAT) exhibits potent advantages regarding target volume coverage and protection of organs at risk, notably in the context of anatomical constraints. Nevertheless, reports concerning VMAT for the treatment of synchronous bilateral breast cancers (SBBC) have been scarce to date. As such, we conducted this observational study to assess efficacy, safety and feasibility of VMAT in SBBC.

Materials and Methods

From August 2011 to December 2017, 54 consecutive patients with SBBC with or without axillary nodes involvement underwent a treatment protocol containing radiotherapy using VMAT. A total dose (TD) of 52.2Gy in 29 fractions was delivered to breast and internal mammary chain (IMC) nodes Planning Target Volume (PTV) plus, if applicable, a TD of 49.3Gy in 29 fractions to the supra- and infra-clavicular nodes PTV and a TD of 63.22Gy in 29 fractions to tumor boost PTV. Lungs, heart, esophagus, trachea, liver, thyroid and spinal cord were considered as organs at risk. VMAT feasibility and organ at risk sparing were evaluated by treatments planning of the 20 first enrolled patients. Tolerance and patients’ outcome were prospectively monitored by acute/late toxicities records and by the analysis of overall survival (OS), locoregional recurrence-free survival (LRFS) and recurrence-free survival (RFS).

Results

Breast, supraclavicular nodes and boost PTV coverage was adequate with at least 98% of PTV encompassed by more than 95% of the prescribed dose. Less than 90% of IMC PTV was encompassed by 95% of the prescribed dose. Mean lung dose was 12.3Gy (range: 7.7 – 18.7); mean heart dose was 10.7Gy (range: 6.2 – 22.3). Concerning acute toxicities, only 2 patients experienced grade 3 skin toxicity (3.7%) and only 1 patient developed grade 1 pneumonitis. After a median follow-up of 5.3 years, grade 2 fibrosis and/or shrinking was observed in 5 patients (10%), and grade 3 fibrosis in 1 patients (2%). The 5-year LRFS-rate, RFS-rate and OS were 98% [95% CI= 86.12-99.70%], 96% [95% CI= 84.63-98.96%] and 100%, respectively.
The low affinity A2B adenosine receptor enhances migratory and invasive capacity in vitro and angiogenesis in vivo of glioblastoma stem-like cells
Authors: Erices José I. , Niechi Ignacio , Uribe-Ojeda Atenea , Toro María de los Ángeles , García-Romero Noemí , Carrión-Navarro Josefa , Monago-Sánchez Álvaro , Ayuso-Sacido Ángel , Martin Rody San , Quezada-Monrás Claudia
Published: August 2022

Glioblastoma (GBM) is the most common and deadly malignant brain tumor, with a median survival of 15 to 17 months for a patient. GBM contains a cellular subpopulation known as GBM stem-like cells (GSCs) that persist in hypoxic niches and are capable of infiltrating into healthy brain tissue. For this reason, GSCs are considered one of the main culprits for GBM recurrence. A hypoxic microenvironment increases extracellular adenosine levels, activating the low affinity A2B adenosine receptor (A2BAR). Adenosine, through A2BAR, is capable of modulating invasiveness. However, its role in the invasion/migration of hypoxic-GSCs is still unknown. This study aims to understand the importance of A2BAR in modulating the migratory/invasive capacity of GSCs under hypoxia. Data analysis from The Cancer Genome Atlas (TCGA) program correlates A2BAR expression with high-grade glioma and hypoxic necrotic areas. U87MG and primary culture-derived GSCs under hypoxic conditions (0.5% O2) increased A2BAR mRNA and protein levels. As expected, the migratory and invasive capacity of GSCs increased under hypoxia, which was counteracted by blocking A2BAR, through the downregulation of MMP9 activity and epithelial–mesenchymal transition marker expression. Finally, in a xenograft mouse model, we demonstrate that treatment with MRS1754 did not affect the tumor volume but could decrease blood vessel formation and VEGF expression. Our results suggest that extracellular adenosine, through the activation of A2BAR, enhances the migratory and invasive capacity of GSCs in vitro under hypoxic conditions. Targeting A2BAR can be an effective therapy for GBM recurrence.
Pro-tumorigenic role of type 2 diabetes-induced cellular senescence in colorectal cancer
Authors: Melia Francesco , Udomjarumanee Palita , Zinovkin Dmitry , Arghiani Nahid , Pranjol Md Zahidul Islam
Published: August 2022

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. The disease still remains incurable and highly lethal in the advanced stage, representing a global health concern. Therefore, it is essential to understand the causes and risk factors leading to its development. Because age-related cellular senescence and type 2 diabetes (T2D) have been recognised as risk factors for CRC development, the recent finding that type 2 diabetic patients present an elevated circulating volume of senescent cells raises the question whether type 2 diabetes facilitates the process of CRC tumorigenesis by inducing premature cell senescence. In this review, we will discuss the mechanisms according to which T2D induces cellular senescence and the role of type 2 diabetes-induced cellular senescence in the pathogenesis and progression of colorectal cancer. Lastly, we will explore the current therapeutic approaches and challenges in targeting senescence.