bluuebunny/crossref_metadata_2025 huggingface dataset:
Fruit scent as an honest signal for fruit quality
Authors: Nevo Omer , Valenta Kim , Helman Annabella , Ganzhorn Jörg U. , Ayasse Manfred
Published: November 2022

Background

Fleshy fruits evolved to be attractive to seed dispersers through various signals such as color and scent. Signals can evolve through different trajectories and have various degrees of reliability. The strongest substrate on which reliable signals can evolve is when there is an inherent link between signal and reward, rendering cheating costly or impossible. It was recently proposed that aliphatic esters in fruit scent may be predictive of sugar content due to their synthesis from products of sugar fermentation. We test this hypothesis on a case study of wild fig species (Ficus tiliifolia) from Madagascar, which relies on seed dispersal by lemurs.

Results

We found a strong positive correlation between signal (esters) and reward (sugar). We also found that non-esters, including direct fermentation products, in fruit scent do not indicate sugar levels, which implies that this relationship is not simply a product of fruit maturation wherein more mature fruits emit more scent and contain more sugar.

Conclusions

While based on a single taxon, these results strongly support the hypothesis that a biochemical link between ester synthesis and sugar may render the ester fraction of fruit scent an honest signal for fruit quality, with consequences for animal sensory and feeding ecology, and the evolution of plants in the context of seed dispersal.
Evolution of the connectivity and indispensability of a transferable gene: the simplicity hypothesis
Authors: Jones C. T. , Susko E. , Bielawski J. P.
Published: November 2022

Background

The number of interactions between a transferable gene or its protein product and genes or gene products native to its microbial host is referred to as connectivity. Such interactions impact the tendency of the gene to be retained by evolution following horizontal gene transfer (HGT) into a microbial population. The complexity hypothesis posits that the protein product of a transferable gene with lower connectivity is more likely to function in a way that is beneficial to a new microbial host compared to the protein product of a transferable gene with higher connectivity. A gene with lower connectivity is consequently more likely to be fixed in any microbial population it enters by HGT. The more recently proposed simplicity hypothesis posits that the connectivity of a transferable gene might increase over time within any single microbial population due to gene-host coevolution, but that differential rates of colonization of microbial populations by HGT in accordance with differences in connectivity might act to counter this and even reduce connectivity over time, comprising an evolutionary trade-off.

Results

We present a theoretical model that can be used to predict the conditions under which gene-host coevolution might increase or decrease the connectivity of a transferable gene over time. We show that the opportunity to enter new microbial populations by HGT can cause the connectivity of a transferable gene to evolve toward lower values, particularly in an environment that is unstable with respect to the function of the gene’s protein product. We also show that a lack of such opportunity in a stable environment can cause the connectivity of a transferable gene to evolve toward higher values.

Conclusion

Our theoretical model suggests that the connectivity of a transferable gene can change over time toward higher values corresponding to a more sessile state of lower transferability or lower values corresponding to a more itinerant state of higher transferability, depending on the ecological milieu in which the gene exists. We note, however, that a better understanding of gene-host coevolutionary dynamics in natural microbial systems is required before any further conclusions about the veracity of the simplicity hypothesis can be drawn.
Evaluating a theory-based intervention for improving eHealth literacy in older adults: a single group, pretest–posttest design
Authors: Chang Sun Ju , Lee Kyoung-eun , Yang Eunjin , Ryu Hyunju
Published: November 2022

Background

The Internet is considered an important channel for providing health information to older adults. We developed an intervention to improve eHealth literacy in older adults according to the information-motivation-behavioral skills (IMB) theory and Intervention Mapping. This study aimed to analyze the effect of a developed intervention on information, motivation, behavioral skills, and behaviors related to eHealth information in older adults.

Methods

Forty-six older adults over the age of 65 were recruited from two senior welfare centers in a city in South Korea. We divided the participants into four groups and conducted one intervention per group from March to December 2019. One intervention consisted of 5 sessions and was performed once a week (2 h/1 time) for 5 weeks, culminating in a total lecture time of 10 h. One lecture instructor and two assistant instructors supported the participants in the computer practices.

Results

Participants’ computer/web knowledge, perceived ease of use, perceived enjoyment, and attitude toward eHealth information showed statistically significant increases. The eHealth literacy efficacy score, searching performance score, and understanding score were also significantly increased. However, there was no significant difference in perceived usefulness.

Conclusion

The application of the current theory-based methodology can improve the quality of research in eHealth literacy. Additionally, various interventions should be developed and continuously applied to improve eHealth literacy among older adults.
Use of proton pump inhibitors and macrolide antibiotics and risk of acute kidney injury: a self-controlled case series study
Authors: Ikuta Keiko , Nakagawa Shunsaku , Yamawaki Chinami , Itohara Kotaro , Hira Daiki , Imai Satoshi , Yonezawa Atsushi , Nakagawa Takayuki , Sakuragi Minoru , Sato Noriaki , Uchino Eiichiro , Yanagita Motoko , Terada Tomohiro
Published: November 2022

Background

Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal disorders such as peptic ulcer disease and dyspepsia. However, several studies have suggested that PPI use increases the risk of acute kidney injury (AKI). PPIs are often concomitantly used with antibiotics, such as macrolides and penicillins for Helicobacter pylori eradication. Although macrolide antibiotics are considered to have relatively low nephrotoxicity, they are well known to increase the risk of AKI due to drug-drug interactions. In this study, we aimed to investigate the association between PPI use and the development of AKI. We also evaluated the effect of concomitant use of PPIs and macrolide antibiotics on the risk of AKI.

Methods

This self-controlled case series study was conducted using electronic medical records at Kyoto University Hospital. We identified patients who were prescribed at least one PPI and macrolide antibiotic between January 2014 and December 2019 and underwent blood examinations at least once a year. An adjusted incident rate ratio (aIRR) of AKI with PPI use or concomitant use macrolide antibiotics with PPIs was estimated using a conditional Poisson regression model controlled for the estimated glomerular filtration rate at the beginning of observation and use of potentially nephrotoxic antibiotics.

Results

Of the 3,685 individuals who received PPIs and macrolide antibiotics, 766 patients with episodes of stage 1 or higher AKI were identified. Any stage of AKI was associated with PPI use (aIRR, 1.80 (95% confidence interval (CI) 1.60 to 2.04)). Stage 2 or higher AKI was observed in 279 cases, with an estimated aIRR of 2.01 (95% CI 1.57 to 2.58, for PPI use). For the period of concomitant use of macrolide antibiotics with PPIs compared with the period of PPIs alone, an aIRR of stage 1 or higher AKI was estimated as 0.82 (95% CI 0.60 to 1.13).

Conclusions

Our findings added epidemiological information for the association between PPI use and an increased risk of stage 1 or higher AKI. However, we did not detect an association between the concomitant use of macrolide antibiotics and an increased risk of AKI in PPI users.
Obese mammary tumour-bearing mice are highly sensitive to doxorubicin-induced hepatotoxicity
Authors: Sedeman Megan , Christowitz Claudia , de Jager Louis , Engelbrecht Anna-Mart
Published: November 2022

Background

Breast cancer is a major health burden for women, worldwide. Lifestyle-related risk factors, such as obesity and being overweight, have reached epidemic proportions and contributes to the development of breast cancer. Doxorubicin (DXR) is a chemotherapeutic drug commonly used to treat breast cancer, and although effective, may cause toxicity to other organs. The mechanisms and effects of DXR on hepatic tissue, and the contributing role of obesity, in breast cancer patients are poorly understood. The aim of this study was therefore to investigate the effects of DXR on hepatic tissue in an obese tumour-bearing mouse model.

Methods

A diet-induced obesity (DIO) mouse model was established, where seventy-four three-week-old female C57BL6 mice were divided into two main groups, namely the high fat diet (containing 60% kcal fat) and standard diet (containing 10% kcal fat) groups. After eight weeks on their respective diets, the DIO phenotype was established, and the mice were further divided into tumour and non-tumour groups. Mice were subcutaneously inoculated with E0771 triple negative breast cancer cells in the fourth mammary gland and received three doses of 4 mg/kg DXR (cumulative dosage of 12 mg/kg) or vehicle treatments via intraperitoneal injection. The expression levels of markers involved in apoptosis and alanine aminotransferase (ALT) were compared by means of western blotting. To assess the pathology and morphology of hepatic tissue, haematoxylin and eosin staining was performed. The presence of fibrosis and lipid accumulation in hepatic tissues were assessed with Masson’s trichrome and Oil Red O staining, respectively.

Results

Microscopic examination of liver tissues showed significant changes in the high fat diet tumour-bearing mice treated with DXR, consisting of macrovesicular steatosis, hepatocyte ballooning and lobular inflammation, compared to the standard diet tumour-bearing mice treated with DXR and the control group (standard diet mice). These changes are the hallmarks of non-alcoholic fatty liver disease, associated with obesity.

Conclusion

The histopathological findings indicated that DXR caused significant hepatic parenchymal injury in the obese tumour-bearing mice. Hepatotoxicity is aggravated in obesity as an underlying co-morbidity. It has been shown that obesity is associated with poor clinical outcomes in patients receiving neo-adjuvant chemotherapy treatment regimens.
Profiles of social constraints and associated factors among breast cancer patients: a latent profile analysis
Authors: Cui ChunYing , Wang Lie , Wang XiaoXi
Published: November 2022

Background

The present study aimed to identify profiles of social constraints among Chinese breast cancer patients and to explore the variables associated with these patterns.

Methods

The study recruited 133 Chinese breast cancer patients in Liaoning Province, China, between June 2021 and February 2022. The questionnaire package included the Social Constraints Scale (SCS), the Multidimensional Scale of Perceived Social Support (MSPSS), the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), and the Social Impact Scale (SIS). The methods of statistical analysis used included latent profile analysis (LPA) and multinomial logistic regression.

Results

Three latent patterns of social constraints were found: class 1-the low social constraints group (51.9%), class 2-the moderate social constraints group (35.3%), and class 3-the high social constraints group (12.8%). Patients with high social support were more likely to report a low level of social constraint, while patients with a greater fear of progression were more likely to report a moderate or high level of social constraints. Significant differences existed among the latent classes identified by reference to social constraint in terms of education.

Conclusion

These results suggest that breast cancer patients’ perceptions of social constraints vary and exhibit individual differences. Health care providers should take into account patients’ fear of progression as well as their social support when developing interventions for patients with a high level of social constraints.
Stress and work-related mental illness among working adults with ADHD: a qualitative study
Authors: Oscarsson Martin , Nelson Martina , Rozental Alexander , Ginsberg Ylva , Carlbring Per , Jönsson Fredrik
Published: November 2022

Background

Though many adults with ADHD underperform professionally, are more stressed, and have more days of sickness absence compared to adults without ADHD, few studies have explored the experience of working as an adult with ADHD. This study explores the general experience of working with ADHD, including stress and work-related mental illness.

Methods

Semi-structured telephone interviews were conducted with 20 working adults with ADHD. Interview topics included how the ADHD diagnosis and/or symptoms of ADHD may have affected participants on the job, how work may have affected participants’ well-being, and the need for support and accommodation. Qualitative content analysis was used to explore verbatim transcripts from the interviews.

Results

The analysis yielded three themes that describe some of the challenges of working with ADHD: Working and living with ADHD, Needs, and Special abilities, with a total of eight subcategories. Subcategories were Specific challenges; Relationships and cooperation; Negative consequences; Planning, prioritization, organization, and structure; Support, interventions, accommodations, and aids; Openness, understanding, and acceptance; Strategies; Strengths and qualities.

Conclusion

Further knowledge about the challenges of working with ADHD is needed in workplaces; where organizational support is lacking, much in terms of accommodations and aids is up to the employee, and the disclosure of diagnoses may be associated with great dilemma.
Appealing dish names to nudge diners to more sustainable food choices: a quasi-experimental study
Authors: Gavrieli Anna , Attwood Sophie , Wise Jonathan , Putnam-Farr Eleanor , Stillman Paul , Giambastiani Scott , Upritchard Jane , Hanson Chavanne , Bakker Michiel
Published: November 2022

Background

Promoting plant-rich diets, i.e., diets with significantly reduced amounts of animal products, including vegan and vegetarian, is a promising strategy to help address the dual environmental and health crises that we currently face. Appealing dish names could boost interest in plant-rich dishes by attracting diners’ attention to them. In this study, a systematic approach to naming plant-rich dishes with appealing descriptors was tested with a quasi-experimental design in four workplace, self-service, buffet-style cafeterias in Chicago, Sydney, São Paulo and Singapore.

Methods

Three different plant-rich dishes were tested at each site. Appealing names were generated systematically through a workshop and emphasized the dish ingredients, origin, flavor and/or the eating experience. Each test dish appeared once in a four-week menu cycle where menu options changed on a daily basis. The cycle was then repeated four times (six times in Chicago) with the total number of showings for each dish to be four (six in Chicago). The dish names alternated between basic and appealing across dish repetitions. For each dish, the food taken per plate was estimated by weighing the overall food taken and dividing it by the plate count in the cafeteria. Data was analysed as percentage change from baseline (i.e., the first showing of each dish that always had a basic name) with linear mixed effects analysis using the lme4 package in R.

Results

Overall, appealing dish names significantly increased the amount of food taken per plate by 43.9% relative to baseline compared to basic dish names (54.5% vs. 10.6% increase for appealing vs. basic names, respectively, p = .002). This increase corresponded to a 7% increase in actual grams of food taken per plate. Secondary analysis showed that the effect was site-specific to English-speaking countries only and that there was no substitution effect between plant-rich and meat dishes.

Conclusions

The study tested an approach to creating appealing dish names in a systematic way and indicates that, in some settings, appealing dish titles are a relatively easy, scalable, cost-effective strategy that the food services sector can adopt to shift food choices towards more plant-rich, sustainable ones.
Epidemiology of sepsis in Beijing from 2012 to 2018: analysis of hospital homepage databases derived from the Beijing Public Health System
Authors: Guo Dong-chen , Zhuang Hai-zhou , Lin Jin , Zhi De-yuan , Duan Mei-li
Published: November 2022

Background

We aimed to evaluate the epidemiology of sepsis in secondary and tertiary hospitals in Beijing, China between 2012 and 2018 using information derived from the Beijing Public Health System.

Methods

The Beijing Public Health System accessed hospital homepage databases and identify patients who diagnosed sepsis or associated condition according to the International Classification of Diseases, 10th Edition, Clinical Modification codes. There are 125 hospitals involved in this study, including 61 secondary hospitals, accounting for 49.2%, and 63 tertiary hospitals, accounting for 50.8%. Patients were stratified by age as minors (0–17 years old), adults (18–64 years old), seniors (65–84 years old), and the elderly (≥ 85 years old). Patient’s demographic information, treatments, outcomes, and all-cause hospitalization cost were evaluated.

Results

This study involved 8,597 patients. Patients treated in tertiary hospitals or received blood transfusion decreased with age, while patients who were male, received ventilation, or took Traditional Chinese Medicine, and in-hospital mortality and hospitalization cost, increased with age. There were 2,729 (31.7%) deaths in this study. A slight increase in in-hospital mortality occurred from 2012 to 2018. Median hospitalization cost for all patients was ¥29,453 (15,011, 65,237). Hospitalization cost showed no significant change from 2012 to 2016, but increased in 2017 and 2018.

Conclusion

Sepsis is associated with high mortality and cost. From 2012 to 2018, in-hospital mortality and hospitalization cost of sepsis in Beijing increased significantly with age, and slightly by year.
Assessing the relationship between knowledge and the actual use of contraceptives among childbearing women in South-South Nigeria: evidence from the 2018 Nigeria demographic and health survey
Authors: Ukoji Vitalis U. , Anele Princewill O. , Imo Chukwuechefulam K.
Published: November 2022

Background

Nigeria has one of the world's highest fertility rates, which is detrimental to its public health and socioeconomic growth. Despite several efforts by the country and other development partners to reduce high fertility by increasing contraceptive use, the contraceptive prevalence rate among childbearing women remains low, particularly in the South-South compared to other Southern regions. This study, therefore, assessed the relationship between knowledge of and actual use of contraception among women in South-South Nigeria.

Methods

The study employed a cross-sectional analysis of a nationally representative weighted sub-sample of 4,553 South-South childbearing women extracted from the 2018 National Demographic and Health Survey dataset. The dataset was weighted and examined for missing values that were excluded during the analyses at univariate, bivariate, and multivariate levels. The analyses involved a baseline descriptive analysis, a chi-square test, and logistic regression models using Stata software. The results of the explanatory variables were presented as odds ratios (OR) and 95% confidence intervals (CI).

Results

Eighty-two per cent of the respondents knew at least one form of contraception, while approximately 82% never used any contraceptive method. The likelihood of using any contraceptive method increased among those who knew about contraceptives (aOR: 1.40; CI: 0.93–2.11). Also, contraceptive use was significantly higher among women and their partners who had post-primary education (aOR: 1.34; CI: 1.25–2.43 and aOR: 1.74; CI: 1.25–2.43, respectively). Furthermore, the prevalence of contraceptive use among women significantly increased with an increase in the household wealth index. Similar results were recorded among women who had five or more living children, who were residents of Rivers State, were married or lived with their partners, were aged 35 years or older, and were currently working.

Conclusions

Contraceptive knowledge was high but did not translate into actual practice among childbearing women in South-South Nigeria. The use of any contraception was highly influenced by contraceptive knowledge, education, age, marital status, place of residence, and household wealth index, among others. Therefore, some policy issues relating to contraceptive knowledge and actual adoption must be addressed to improve the low rate of contraceptive use in Nigeria.
Investigating the residual effect of silver nanoparticles gel as an intra-canal medicament on dental pulp stromal cells
Authors: Mahmoud Ahmed , Moussa Sybel , El Backly Rania , El-Gendy Reem
Published: November 2022

Background

The aim of this study was to evaluate the indirect effects of residual silver nanoparticles (AgNPs) gel on human dental pulp stromal cells (DPSCs).

Methods

Ninety-five dentin discs (4x4x1 mm) were prepared from freshly extracted human single-rooted teeth following institutional ethical approval and informed consent. Samples were cleaned, autoclaved, and treated with: 1.5%NaOCl, Saline and 17% EDTA then randomly assigned to 5 groups that received 50 μl of one of the following treatments: 0.01%AgNPs, 0.015%AgNPs, 0.02%AgNPs, Calcium hydroxide (Ca (OH)2) or no treatment for 1 week. Discs were washed with Saline and 17%EDTA then seeded with DPSCs and incubated for 3 and 7 days. At 24 hours unattached cells were collected and counted. At each time point cytotoxicity (LDH assay), cell viability (live/dead staining and confocal microscopy) and cell proliferation (WST1 assay) were assessed. All experiments were repeated a minimum of 3 times using DPSCs isolated from 3 different donors for each time point assessed (n = 9/group). Statistical analysis was done using One-Way ANOVA followed by Tukey’s test and Kruskal Wallis followed by post-hoc comparisons with significance set at p ≤ 0.05.

Results

After 24 hours, the percentage of DPSCs attachment ranged between 92.66% ±4.54 and 95.08% ±1.44 with no significant difference between groups (P = 0.126). Cell viability was ≥92% at 24 hours for all groups. However this percentage dropped to less than 60% at 3 days then started to rise again at 7 days. There was no significant difference in cytotoxicity between different groups at all time points except for 0.01%AgNPs group which had the highest cytotoxicity. DPSCs proliferation increased significantly from 3 to 7 days in all groups except for Ca (OH)2 which showed lower proliferation rates at both 3 (45.89%) and 7 days (79.25%).

Conclusion

Dentin discs treated for 7 days with concentrations of AgNPs gel (0.01–0.02%) allowed more than 90% DPSCs cell attachment after 24 hours. The cytotoxicity and proliferation of DPSCs in response to AgNPs gel were comparable to those with calcium hydroxide. This suggests that AgNPs gel may represent a promising future candidate for clinical use in regenerative endodontics. However, its effects may be concentration-dependent warranting further investigation.
Synthetic Micrographs of Bacteria (SyMBac) allows accurate segmentation of bacterial cells using deep neural networks
Authors: Hardo Georgeos , Noka Maximilian , Bakshi Somenath
Published: November 2022

Background

Deep-learning–based image segmentation models are required for accurate processing of high-throughput timelapse imaging data of bacterial cells. However, the performance of any such model strictly depends on the quality and quantity of training data, which is difficult to generate for bacterial cell images. Here, we present a novel method of bacterial image segmentation using machine learning models trained with Synthetic Micrographs of Bacteria (SyMBac).

Results

We have developed SyMBac, a tool that allows for rapid, automatic creation of arbitrary amounts of training data, combining detailed models of cell growth, physical interactions, and microscope optics to create synthetic images which closely resemble real micrographs, and is capable of training accurate image segmentation models. The major advantages of our approach are as follows: (1) synthetic training data can be generated virtually instantly and on demand; (2) these synthetic images are accompanied by perfect ground truth positions of cells, meaning no data curation is required; (3) different biological conditions, imaging platforms, and imaging modalities can be rapidly simulated, meaning any change in one’s experimental setup no longer requires the laborious process of manually generating new training data for each change. Deep-learning models trained with SyMBac data are capable of analysing data from various imaging platforms and are robust to drastic changes in cell size and morphology. Our benchmarking results demonstrate that models trained on SyMBac data generate more accurate cell identifications and precise cell masks than those trained on human-annotated data, because the model learns the true position of the cell irrespective of imaging artefacts. We illustrate the approach by analysing the growth and size regulation of bacterial cells during entry and exit from dormancy, which revealed novel insights about the physiological dynamics of cells under various growth conditions.

Conclusions

The SyMBac approach will help to adapt and improve the performance of deep-learning–based image segmentation models for accurate processing of high-throughput timelapse image data.
A genome-wide association study identifies a novel association between SDC3 and apparent treatment-resistant hypertension
Authors: Xiao Xiao , Li Rui , Wu Cunjin , Yan Yupeng , Yuan Mengmeng , Cui Bing , Zhang Yu , Zhang Channa , Zhang Xiaoxia , Zhang Weili , Hui Rutai , Wang Yibo
Published: November 2022

Background

Compared with patients who require fewer antihypertensive agents, those with apparent treatment-resistant hypertension (aTRH) are at increased risk for cardiovascular and all-cause mortality, independent of blood pressure control. However, the etiopathogenesis of aTRH is still poorly elucidated.

Methods

We performed a genome-wide association study (GWAS) in first cohort including 586 aTRHs and 871 healthy controls. Next, expression quantitative trait locus (eQTL) analysis was used to identify genes that are regulated by single nucleotide polymorphisms (SNPs) derived from the GWAS. Then, we verified the genes obtained from the eQTL analysis in the validation cohort including 65 aTRHs, 96 hypertensives, and 100 healthy controls through gene expression profiling analysis and real-time quantitative polymerase chain reaction (RT-qPCR) assay.

Results

The GWAS in first cohort revealed four suggestive loci (1p35, 4q13.2-21.1, 5q22-23.2, and 15q11.1-q12) represented by 23 SNPs. The 23 significant SNPs were in or nearLAPTM5,SDC3,UGT2A1,FTMT, andNIPA1.eQTL analysis uncovered 14 SNPs in 1p35 locus all had same regulation directions forSDC3andLAPTM5. The disease susceptible alleles of SNPs in 1p35 locus were associated with lower gene expression forSDC3and higher gene expression forLAPTM5.The disease susceptible alleles of SNPs in 4q13.2-21.1 were associated with higher gene expression forUGT2B4. GTEx database did not show any statistically significant eQTLs between the SNPs in 5q22-23.2 and 15q11.1-q12 loci and their influenced genes. Then, gene expression profiling analysis in the validation cohort confirmed lower expression ofSDC3in aTRH but no significant differences onLAPTM5andUGT2B4, when compared with controls and hypertensives, respectively. RT-qPCR assay further verified the lower expression ofSDC3in aTRH.

Conclusions

Our study identified a novel association ofSDC3with aTRH, which contributes to the elucidation of its etiopathogenesis and provides a promising therapeutic target.
Specific lncRNA signatures discriminate childhood acute leukaemias: a pilot study
Authors: Buono Lorena , Iside Concetta , De Matteo Antonia , Stellato Pio , Beneduce Giuliana , de Vera d’Aragona Roberta Penta , Parasole Rosanna , Salvatore Marco , Smaldone Giovanni , Mirabelli Peppino
Published: November 2022

Background

Long non-coding RNAs are RNAs longer than 200 bps that do not encode any proteins and are able to alter gene expression by acting on different steps of regulation, including DNA methylation and chromatin structure. They represent a class of biomarkers of crescent interest in the hematologic and oncologic fields. Recent studies showed that the expression levels of specific lncRNAs correlate with the prognosis of paediatric patients with Acute Lymphoblastic Leukaemia.

Methods

We used NGS approaches to analyse the transcriptome of 9 childhood B-ALL patients and 6 childhood T-ALL patients, in comparison with B and T healthy lymphocytes from cord blood. We validate our findings both ex vivo, in a different cohort of 10 B-ALL and 10 T-ALL patients, and in silico using public datasets.

Results

We characterised the lncRNA landscape for B-ALL, T-ALL, healthy B, and T cell progenitors. From the characterised signature, we selected candidate lncRNAs able to discriminate not only B-ALL and T-ALL from healthy subjects but also between the two types of leukaemia, and subsequently validated their potential as a diagnostic tool in an additional cohort of paediatric patients. We confirmed our finding with open access transcriptomic data, comparing ALL lncRNAs with AML lncRNA landscape as well. Finally, expression correlation analyses of T-ALL selected lncRNA biomarkers suggested a possible role in lymphocyte activation and the β-catenin signalling pathway for AC247036.1 and involvement in hedgehog signalling for HHIP-AS1.

Conclusions

Our work identified a lncRNA signature discriminating paediatric B-ALL and T-ALL from healthy subjects, between them and from AML. This study provides the keystone to future clinical studies determining the theragnostic value of the characterised long non coding transcriptome panorama in a clinical setting for childhood patient management.
Global–local multi-stage temporal convolutional network for cataract surgery phase recognition
Authors: Fang Lixin , Mou Lei , Gu Yuanyuan , Hu Yan , Chen Bang , Chen Xu , Wang Yang , Liu Jiang , Zhao Yitian
Published: November 2022

Background

Surgical video phase recognition is an essential technique in computer-assisted surgical systems for monitoring surgical procedures, which can assist surgeons in standardizing procedures and enhancing postsurgical assessment and indexing. However, the high similarity between the phases and temporal variations of cataract videos still poses the greatest challenge for video phase recognition.

Methods

In this paper, we introduce a global–local multi-stage temporal convolutional network (GL-MSTCN) to explore the subtle differences between high similarity surgical phases and mitigate the temporal variations of surgical videos. The presented work consists of a triple-stream network (i.e., pupil stream, instrument stream, and video frame stream) and a multi-stage temporal convolutional network. The triple-stream network first detects the pupil and surgical instruments regions in the frame separately and then obtains the fine-grained semantic features of the video frames. The proposed multi-stage temporal convolutional network improves the surgical phase recognition performance by capturing longer time series features through dilated convolutional layers with varying receptive fields.

Results

Our method is thoroughly validated on the CSVideo dataset with 32 cataract surgery videos and the public Cataract101 dataset with 101 cataract surgery videos, outperforming state-of-the-art approaches with 95.8% and 96.5% accuracy, respectively.

Conclusions

The experimental results show that the use of global and local feature information can effectively enhance the model to explore fine-grained features and mitigate temporal and spatial variations, thus improving the surgical phase recognition performance of the proposed GL-MSTCN.
Determinants of delayed onset of lactogenesis II among women who delivered via Cesarean section at a tertiary hospital in China: a prospective cohort study
Authors: Lian Weining , Ding Juan , Xiong Tiantian , Liuding Jiandi , Nie LinTao
Published: November 2022

Background

Cesarean birth is associated with a higher prevalence of delayed onset of lactogenesis II (DOLII) than vaginal birth. DOLII refers to the delayed initiation of copious milk production beyond 72 h after birth. This study aimed to determine the prevalence of, and factors associated with, DOLII among women who delivered via Cesarean section in China.

Methods

This prospective longitudinal cohort study recruited 468 women who delivered via Cesarean section at a tertiary hospital in China from 9 October 2021 to 17 May 2022. Face-to-face interviews were conducted during their delivery hospital stay to obtain information about demographic, medical, and breastfeeding factors. We assessed the onset of lactogenesis on postpartum day four, based on the maternal perception of changes in breast fullness. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for postpartum depression. Women with DOLII were interviewed via telephone or WeChat daily for one week postpartum to determine the timing of the onset of lactogenesis II. Univariate and multivariable logistic regression analyses were used to identify the determinants of DOLII.

Results

DOLII was experienced by 156 of 468 participants (33.3%). After adjusting for potential confounders, the odds of DOLII were 95% higher in primiparous women than multiparous women (adjusted odds ratio [aOR] 1.95; 95% confidence interval [CI] 1.29, 2.98), 75% higher in women with a serum albumin concentration < 35 g / L than women with normal serum albumin concentrations (aOR 1.78; 95% CI 1.09, 2.99), increased by 2.03-fold in women with an EPDS score ≥ 10 than women with an EPDS score < 10 (aOR 2.03; 95% CI 1.35, 3.07), and decreased in women with a higher number of breastfeeding sessions in the first 48 h postpartum (aOR 0.88; 95% CI 0.83, 0.93).

Conclusions

One-third of women with Cesarean section delivery experienced DOLII. DOLII was more likely in women who were primiparous, had a serum albumin concentration < 35 g / L, had a lower frequency of breastfeeding sessions, and had an EPDS score ≥ 10. Women with these risk factors who deliver via Cesarean section may need early breastfeeding support to ensure successful lactation.
Recurrent co-domestication of PIF/Harbinger transposable element proteins in insects
Authors: Markova Dragomira N. , Ruma Fatema B. , Casola Claudio , Mirsalehi Ayda , Betrán Esther
Published: November 2022

Background

Transposable elements (TEs) are selfish DNA sequences capable of moving and amplifying at the expense of host cells. Despite this, an increasing number of studies have revealed that TE proteins are important contributors to the emergence of novel host proteins through molecular domestication. We previously described seven transposase-derived domesticated genes from the PIF/Harbinger DNA family of TEs in Drosophila and a co-domestication. All PIF TEs known in plants and animals distinguish themselves from other DNA transposons by the presence of two genes. We hypothesize that there should often be co-domestications of the two genes from the same TE because the transposase (gene 1) has been described to be translocated to the nucleus by the MADF protein (gene 2). To provide support for this model of new gene origination, we investigated available insect species genomes for additional evidence of PIF TE domestication events and explored the co-domestication of the MADF protein from the same TE insertion.

Results

After the extensive insect species genomes exploration of hits to PIF transposases and analyses of their context and evolution, we present evidence of at least six independent PIF transposable elements proteins domestication events in insects: two co-domestications of both transposase and MADF proteins in Anopheles (Diptera), one transposase-only domestication event and one co-domestication in butterflies and moths (Lepidoptera), and two transposases-only domestication events in cockroaches (Blattodea). The predicted nuclear localization signals for many of those proteins and dicistronic transcription in some instances support the functional associations of co-domesticated transposase and MADF proteins.

Conclusions

Our results add to a co-domestication that we previously described in fruit fly genomes and support that new gene origination through domestication of a PIF transposase is frequently accompanied by the co-domestication of a cognate MADF protein in insects, potentially for regulatory functions. We propose a detailed model that predicts that PIF TE protein co-domestication should often occur from the same PIF TE insertion.
Are peanut oral food challenges still useful? An evaluation of children with suspected peanut allergy, sensitization to Ara h 2 and controlled asthma
Authors: Ojaniemi Iida , Salmivesi Susanna , Tikkakoski Antti , Karjalainen Jussi , Lehtimäki Lauri , Schultz Rüdiger
Published: November 2022

Background

Sensitization to Ara h 2 has been proposed as a promising biological marker for the severity of peanut allergy and may reduce the need for oral food challenges. This study aimed to evaluate whether peanut oral food challenge is still a useful diagnostic tool for children with suspected peanut allergy and an elevated level of Ara h 2-specific IgE. Additionally, we assessed whether well-controlled asthma is an additional risk for severe reactions.

Methods

A retrospective analysis of 107 children with sensitization to Ara h 2-specific IgE (> 0.35 kU/l) undergoing open peanut challenges during 2012–2018 in the Tampere University Hospital Allergy Centre, Finland.

Results

Of the 107 challenges, 82 (77%) were positive. Serum levels of Ara h 2 -sIgE were higher in subjects with a positive challenge than in those who remained negative (median 32.9 (IQR 6.7–99.8) vs. 2.1 (IQR 1.0–4.9) kU/l), p < 0.001) but were not significantly different between subjects with and without anaphylaxis. No correlation was observed between the serum level of Ara h 2-sIgE and reaction severity grading. Well-controlled asthma did not affect the challenge outcome.

Conclusions

Elevated levels of Ara h 2-specific IgE are associated with a positive outcome in peanut challenges but not a reliable predictor of reaction severity. Additionally, well-controlled asthma is not a risk factor for severe reactions in peanut challenges in children with sensitization to Ara h 2.
Advice for lay callers with low-risk poison exposures by a regional poison control center: the impact on health care expenditures
Authors: Thal Franziska , Reinhold Thomas
Published: November 2022

Background

Since establishing the first poison control centers (PCCs), there is a still ongoing debate regarding their relevance and financing. The present study aims to analyze whether a regional PCC can reduce the economic burden associated with utilization of health care structures due to low-risk poison exposures on the German health care system.

Methods

A decision-tree based cost–benefit analysis comparing a situation utilizing PCC consultation versus a hypothetical situation without PCC consultation for low-risk poison exposures from the German health care system's perspective was conducted. The model inputs were obtained by a representative telephone survey of lay callers supplemented by empirical PCC and literature data. A probabilistic and deterministic sensitivity analysis with varying input variables was performed to prove the robustness of the findings.

Results

In the underlying telephone survey, data of 378 lay callers could be considered and included in the decision tree model. As a result, the mean costs for handling one low-risk poison exposure case were €41.99 utilizing PCC consultation compared to €145.92 without PCC consultation, indicating a cost–benefit ratio of 3.48 for the existence of the PCC. The sensitivity analysis proved that the outcome of the decision analysis does not change significantly with varying inputs.

Conclusion

The existence of PCCs relieve the burden on other health care providers and reduce health care costs to a relevant extent. Therefore, PCCs should be considered as an important supporting structure of the German health care system.
Implementation of a decentralized hepatitis C care pathway for people who use drugs in Dutch addiction care. Study protocol for the Hepatitis C: chain of addiction care (CAC) project
Authors: Von den Hoff Daan W. , Berden Floor A. C. , Drenth Joost P. H. , Schellekens Arnt F. A. ,   HepNed, NISPA
Published: November 2022

Background

People who use drugs (PWUD) are at high risk for hepatitis C virus (HCV) infection and its complications. Given the high prevalence rate of HCV in PWUD, the World Health Organization (WHO) emphasizes PWUD as a target population for HCV elimination. The introduction of pangenotypic direct acting antivirals (DAAs) greatly simplifies HCV treatment, which encourages integration of HCV treatment in primary care. Facilitating low threshold HCV care for PWUD by implementing decentralized models is crucial for HCV elimination.

Aims

With this study we aim to (1) eliminate 90% of identified HCV infections in Dutch addiction care, using a decentralized PWUD-HCV care model, and (2) identify facilitators and barriers for successful implementation of the model using interviews.

Methods

We will perform a multicenter mixed-method study on HCV treatment in addiction care. In a prospective observational study we will examine HCV-related outcomes in PWUD receiving HCV treatment as part of addiction care. The primary outcome is viral elimination, defined as percentage of identified HCV positive patients cured with DAAs. In parallel, we will perform a qualitative study to explore facilitators and barriers for implementation of fully decentralized HCV-PWUD care. We will interview addiction care professionals and board members about their experience with HCV-care as part of addiction care.

Discussion

This study will show effectiveness of integration of HCV care within addiction care, and provide insight in facilitators and barriers to implement integrated HCV-addiction care. The results will provide recommendations for implementation and maintenance of the decentralized HCV pathway, which can facilitate scaling-up to contribute to reaching WHO HCV elimination goals.

Trial registration NCT05401136.
Safety of linezolid in patients with decreased renal function and trough monitoring: a systematic review and meta-analysis
Authors: Liu Xiaoxi , Aoki Mari , Osa Sumika , Ito Chihiro , Saiki Reika , Nagai Tomoya , Enoki Yuki , Taguchi Kazuaki , Matsumoto Kazuaki
Published: November 2022

Background

Linezolid causes hematological toxicity, mostly thrombocytopenia, which leads to treatment discontinuation and failure. Recent studies revealed that during linezolid therapy, the incidence of treatment-related hematological toxicity is significantly higher in patients with decreased renal function (DRF) than in those with normal renal function. Linezolid monitoring is necessary due to the high frequency of hematological toxicity in patients with DRF and the relationship between blood concentration and safety. We performed a systematic review and meta-analysis to evaluate the safety correlation between DRF and trough monitoring.

Methods

Articles published before June 24, 2022, on MEDLINE, Web of Sciences, Cochrane Register of Controlled Trials, and ClinicalTrials.gov were systematically analyzed. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel method and the variable effects model.

Results

The incidence of hematological toxicity was significantly higher in patients with DRF than in those without DRF (OR = 2.37; p < 0.001). Subgroup analysis, performed according to hematotoxicity classification, including thrombocytopenia, anemia, and pancytopenia, revealed a significantly higher incidence of thrombocytopenia (OR = 2.45; p < 0.001) and anemia (OR = 2.31; p = 0.006) in patients with DRF than in those without; pancytopenia (OR = 1.41; p = 0.80) incidences were not significantly higher. Based on a systematic review, linezolid trough concentrations > 6–7 μg/mL may be associated with an increased incidence of thrombocytopenia. However, no confidential threshold values for the development of thrombocytopenia were found in the area under the concentration curve values for children or adults.

Conclusion

We observed a high frequency of hematological toxicity during linezolid therapy in patients with DRF. To ensure safety, linezolid trough concentrations should be ≤6–7 μg/mL.
Methylation differences in Alzheimer’s disease neuropathologic change in the aged human brain
Authors: Lang Anna-Lena , Eulalio Tiffany , Fox Eddie , Yakabi Koya , Bukhari Syed A. , Kawas Claudia H. , Corrada Maria M. , Montgomery Stephen B. , Heppner Frank L. , Capper David , Nachun Daniel , Montine Thomas J.
Published: November 2022

Alzheimer’s disease (AD) is the most common cause of dementia with advancing age as its strongest risk factor. AD neuropathologic change (ADNC) is known to be associated with numerous DNA methylation changes in the human brain, but the oldest old (> 90 years) have so far been underrepresented in epigenetic studies of ADNC. Our study participants were individuals aged over 90 years (n = 47) from The 90+ Study. We analyzed DNA methylation from bulk samples in eight precisely dissected regions of the human brain: middle frontal gyrus, cingulate gyrus, entorhinal cortex, dentate gyrus, CA1, substantia nigra, locus coeruleus and cerebellar cortex. We deconvolved our bulk data into cell-type-specific (CTS) signals using computational methods. CTS methylation differences were analyzed across different levels of ADNC. The highest amount of ADNC related methylation differences was found in the dentate gyrus, a region that has so far been underrepresented in large scale multi-omic studies. In neurons of the dentate gyrus, DNA methylation significantly differed with increased burden of amyloid beta (Aβ) plaques at 5897 promoter regions of protein-coding genes. Amongst these, higher Aβ plaque burden was associated with promoter hypomethylation of the Presenilin enhancer 2 (PEN-2) gene, one of the rate limiting genes in the formation of gamma-secretase, a multicomponent complex that is responsible in part for the endoproteolytic cleavage of amyloid precursor protein into Aβ peptides. In addition to novel ADNC related DNA methylation changes, we present the most detailed array-based methylation survey of the old aged human brain to date. Our open-sourced dataset can serve as a brain region reference panel for future studies and help advance research in aging and neurodegenerative diseases.