bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundDeep-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).ResultsWe 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.ConclusionsThe 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

AbstractBackgroundCompared 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.MethodsWe 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.ResultsThe 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.ConclusionsOur 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractAlzheimer’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.