bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality control recommendations for RNASeq using FFPE samples based on pre-sequencing lab metrics and post-sequencing bioinformatics metrics
Authors: Liu Yuanhang , Bhagwate Aditya , Winham Stacey J. , Stephens Melissa T. , Harker Brent W. , McDonough Samantha J. , Stallings-Mann Melody L. , Heinzen Ethan P. , Vierkant Robert A. , Hoskin Tanya L. , Frost Marlene H. , Carter Jodi M. , Pfrender Michael E. , Littlepage Laurie , Radisky Derek C. , Cunningham Julie M. , Degnim Amy C. , Wang Chen
Published: September 2022

Background

Formalin-fixed, paraffin-embedded (FFPE) tissues have many advantages for identification of risk biomarkers, including wide availability and potential for extended follow-up endpoints. However, RNA derived from archival FFPE samples has limited quality. Here we identified parameters that determine which FFPE samples have the potential for successful RNA extraction, library preparation, and generation of usable RNAseq data.

Methods

We optimized library preparation protocols designed for use with FFPE samples using seven FFPE and Fresh Frozen replicate pairs, and tested optimized protocols using a study set of 130 FFPE biopsies from women with benign breast disease. Metrics from RNA extraction and preparation procedures were collected and compared with bioinformatics sequencing summary statistics. Finally, a decision tree model was built to learn the relationship between pre-sequencing lab metrics and qc pass/fail status as determined by bioinformatics metrics.

Results

Samples that failed bioinformatics qc tended to have low median sample-wise correlation within the cohort (Spearman correlation < 0.75), low number of reads mapped to gene regions (< 25 million), or low number of detectable genes (11,400 # of detected genes with TPM > 4). The median RNA concentration and pre-capture library Qubit values for qc failed samples were 18.9 ng/ul and 2.08 ng/ul respectively, which were significantly lower than those of qc pass samples (40.8 ng/ul and 5.82 ng/ul). We built a decision tree model based on input RNA concentration, input library qubit values, and achieved an F score of 0.848 in predicting QC status (pass/fail) of FFPE samples.

Conclusions

We provide a bioinformatics quality control recommendation for FFPE samples from breast tissue by evaluating bioinformatic and sample metrics. Our results suggest a minimum concentration of 25 ng/ul FFPE-extracted RNA for library preparation and 1.7 ng/ul pre-capture library output to achieve adequate RNA-seq data for downstream bioinformatics analysis.
Effect of dapagliflozin on the prognosis of patients with acute myocardial infarction undergoing percutaneous coronary intervention
Authors: Zhu Yi , Zhang Jia-li , Yan Xue-jiao , Sun Ling , Ji Yuan , Wang Fang-fang
Published: September 2022

Background and aims

The effect of dapagliflozin (DAPA) on the prognosis of patients with acute myocardial infarction (AMI) is unclear. The present study was conducted to evaluate the association between DAPA administration and adverse events in patients with AMI undergoing percutaneous coronary intervention (PCI).

Methods

This single-center retrospective analysis study included a total of 786 patients with AMI from January 2019 to August 2021 who were or were not administered DAPA at discharge. The primary endpoint was the composite of major adverse cardiovascular events (MACE), including overall deaths, heart failure, nonfatal MI, nonfatal stroke, and unplanned repeat revascularization (URR). Differences in the triglyceride glucose (TyG) index and the atherogenic index of plasma (AIP) both during hospitalization and 12 months after discharge (if achievable) were also compared.

Results

During a median follow-up of 23 months, 130 patients had MACE (118 in the DAPA-free group and 12 in the DAPA group). Kaplan–Meier survival analyses revealed that the cumulative incidence of MACE (log-rank test, p = 0.009), heart failure (p = 0.003), nonfatal MI (p = 0.005), and URR (p = 0.031) was higher in the DAPA-free group. In addition, the multivariate Cox analysis showed that DAPA was significantly associated with the reduced risk of MACE (hazard ratio = 0.170, 95% confidence interval = 0.078–0.373, p < 0.001). Considering each specific adverse event, the DAPA-free group was associated with heart failure, nonfatal MI, and URR in multivariate Cox regression analyses. Stratification analyses suggested that DAPA has a strong protective effect in patients with AMI of advanced age with concomitant diabetes or those who are not on angiotensin receptor enkephalinase inhibitors. Furthermore, the TyG index and AIP of the patients 12 months after DAPA administration at discharge were significantly lower than those during hospitalization.

Conclusions

DAPA is an independent protective factor against MACE and may provide incremental prognostic information in patients with AMI undergoing PCI.
Dietary and drinking water intake of essential trace elements in a typical Kashin-Beck disease endemic area of Tibet, China
Authors: Zha Xinjie , An Jialu , Gao Xue , Tian Yuan
Published: September 2022

Background

Essential trace elements (ETEs), such as copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), zinc (Zn), are very important elements for human health.

Methods

In this study, 89 drinking water samples and 85 highland barleys were collected from 48 villages in 11 townships, and the average daily dose (ADD) of ETEs were calculated, in addition, health effects of ETEs to rural residents in Luolong County, a typical Kashin-Beck disease (KBD) endemic area in Tibet, were assessed.

Results

The mean concentrations of Cu, Fe, Mn, Mo, Se, Zn in drinking water were 0.278 ± 0.264 μg·kg−1, 0.766 ± 0.312 μg·kg−1, 0.411 ± 0.526 μg·kg−1, 0.119 ± 0.223 μg·kg−1, 0.155 ± 0.180 μg·kg−1, and 0.804 ± 1.112 μg·kg−1, respectively; and mean concentrations of Cu, Fe, Mn, Mo, Se and Zn in highland barley were 3.550 ± 0.680 mg·kg−1, 81.17 ± 38.14 mg·kg−1, 14.03 ± 1.42 mg·kg−1, 0.350 ± 0.200 mg·kg−1, 0.0028 ± 0.0056 mg·kg−1, and 23.58 ± 3.10 mg·kg−1, respectively. The ADD of Cu in the study area was appropriate; the ADD of Fe and Mn in each township were higher than the maximum oral reference dose recommended by the National Health Commission of China, indicating that Fe and Mn had non-carcinogenic health risks; the ADD of Mo and Zn in 36.36% and 54.55% of the townships exceeded the maximum oral reference dose; and 72.73% of the townships had insufficient ADD of Se. The ADD of Mo, Cu and Se in different townships was significantly correlated with the prevalence of KBD.

Conclusions

Therefore, in order to prevent and control the prevalence of KBD and ensure the health of local residents, it is necessary to reduce the intake of high concentrations of Fe, Mn and Zn in diet, as well as increase the intake of Mo, Cu, especially Se.

Graphical abstract
Alcohol-dependent downregulation of apolipoprotein H exacerbates fatty liver and gut microbiota dysbiosis in mice
Authors: Liu Yaming , Wu Zhe , Zhang Yong , Chen Binbin , Yu Shuqi , Li Wanyun , Ren Jianlin
Published: September 2022

Background

Alcohol-related liver disease (ALD) is a major chronic liver ailment caused by alcohol overconsumption and abuse. Apolipoprotein H (APOH) participates in lipid metabolism and might have a potential regulatory role in ALD. Therefore, this study aimed to explore the effects of ApoH on alcohol-induced liver injury and gut microbiota dysbiosis.

Methods

ApoH−/− mice were generated and the synergic alcoholic steatohepatitis mouse model was constructed, which were used to assess liver function and pathological changes.

Results

ApoH−/− mice clearly exhibited spontaneous steatohepatitis. Severe hepatic steatosis was observed in alcohol-fed WT and ApoH−/− mice, in which ApoH expression was reduced post alcohol consumption. Moreover, RNA-seq and KEGG pathway analyses indicated that differential expression genes enriched in lipid metabolism and oxidation–reduction process between in alcohol-fed ApoH−/− mice and pair-fed control mice. Finally, gut microbiota diversity and composition were assessed by 16S rRNA Illumina next-generation sequencing. Alpha diversity of enterobacteria was lower in ApoH−/− mice with ethanol feeding than in ethanol-fed WT mice and all control-fed mice (P < 0.05). Moreover, KEGG enrichment analysis, using PICRUSt software, revealed that metabolic functions were activated in the gut microorganisms of ApoH−/− mice with ethanol feeding (P < 0.05).

Conclusions

Alcohol-downregulated ApoH expression, leading to the progress of fatty liver disease and gut microbiota dysbiosis.
The clinicopathological and prognostic factors of hepatocellular carcinoma: a 10-year tertiary center experience in Egypt
Authors: Sweed Dina , Sweed Enas , Moaz Inas , Mosbeh Asmaa , Fayed Yahya , Elhamed Sara Mohamed Abd , Sweed Eman , Macshut Mahmoud , Abdelsattar Shimaa , Kilany Shimaa , Saied Sara A. , Badr Reda , Abdallah Mahmoud S. , Ehsan Nermine
Published: September 2022

Background

Hepatocellular carcinoma (HCC) remains a major health problem despite the emergence of several preventive and therapeutic modalities. HCC has heterogeneous and wide morpho-molecular patterns, resulting in unique clinical and prognostic criteria. Therefore, we aimed to study the clinical and pathological criteria of HCC to update the morpho-molecular classifications and provide a guide to the diagnosis of this disease.

Methods

Five hundred thirty pathologically analyzed HCC cases were included in this study. The clinical and survival data of these cases were collected.

Results

Hepatitis C virus is still the dominant cause of HCC in Egypt. Post-direct-acting antiviral agent HCC showed an aggressive course compared to interferon-related HCC. Old age, male gender, elevated alpha-fetoprotein level, tumor size, and background liver were important prognostic parameters. Special HCC variants have characteristic clinical, laboratory, radiological, prognostic, and survival data. Tumor-infiltrating lymphocytes rather than neutrophil-rich HCC have an excellent prognosis.

Conclusions

HCC is a heterogenous tumor with diverse clinical, pathological, and prognostic parameters. Incorporating the clinicopathological profile per specific subtype is essential in the treatment decision of patients with HCC.

Trial registration

This was a retrospective study that included 530 HCC cases eligible for analysis. The cases were obtained from the archives of the Pathology Department, during the period between January 2010 and December 2019. Clinical and survival data were collected from the patients’ medical records after approval by the institutional review board (IRB No. 246/2021) of Liver National Institute, Menoufia University. The research followed the guidelines outlined in the Declaration of Helsinki and registered on ClinicalTrials.gov (NCT05047146).
A systematic review of the economic evaluations of Enzyme Replacement Therapy in Lysosomal Storage Diseases
Authors: Katsigianni Eleni Ioanna , Petrou Panagiotis
Published: September 2022

Objective

The objective of this paper is to assess the economic profile of Enzyme Replacement Therapy (ERT) to symptomatic patients with Pompe, Fabry, Gaucher disease and Lysosomal acid lipase (LAL) deficiency.

Methods

A systematic search was performed to retrieve and critically assess economic evaluations of enzyme replacement therapy. Publications were screened according to predefined criteria and evaluated according to the Quality of Economic Studies. Data were narratively synthesized.

Results

The Incremental Cost-Effectiveness Ratio greatly exceeded willingness to pay thresholds. The cost of the medication dominated the sensitivity analysis. For Infantile-onset Pompe’s disease, the incremental cost-effectiveness ratio (ICER) was estimated at €1.043.868 per Quality-adjusted life year (QALY) based on the dose of alglucosidase 40 mg/kg/ week, and €286.114 per QALY for 20 mg of alglucosidase/kg/2 weeks. For adults patients presenting with Pompe disease the reported was ICER € 1.8 million/ QALY. In the case of Fabry disease, the ICER per QALY amounts to 6.1 million Euros/QALY. Respectively for Gaucher’s disease, the ICER /QALY was estimated at € 884,994 per QALY. Finally, for patients presenting LAL deficiency NCPE perpetuated an ICER of €2,701,000/QALY.

Discussion

ERT comprise a promising treatment modality for orphan diseases; nevertheless, it is interlaced with a substantial economic burden. Moreover, the available data on the cost-effectiveness ratio are scarce. For certain diseases, such as Fabry, a thorough selection of patients could exert a beneficial effect on the reported ICER. Steep price reductions are imperative for these products, in the conventional reimbursement pathway or a new assessment framework should be elaborated, which in principle, should target uncertainty.
The role of DNA demethylation in liver to pancreas transdifferentiation
Authors: Har-Zahav Adi , Lixandru Daniela , Cheishvili David , Matei Ioan Valentin , Florea Ioana Raluca , Aspritoiu Veronica Madalina , Blus-Kadosh Inna , Meivar-Levy Irit , Serban Andreea Madalina , Popescu Irinel , Szyf Moshe , Ferber Sarah , Dima Simona Olimpia
Published: September 2022

Background

Insulin producing cells generated by liver cell transdifferentiation, could serve as an attractive source for regenerative medicine. The present study assesses the relationship between DNA methylation pTFs induced liver to pancreas transdifferentiation.

Results

The transdifferentiation process is associated with DNA demethylation, mainly at gene regulatory sites, and with increased expression of these genes. Active inhibition of DNA methylation promotes the pancreatic transcription factor-induced transdifferentiation process, supporting a causal role for DNA demethylation in this process.

Conclusions

Transdifferentiation is associated with global DNA hypomethylation, and with increased expression of specific demethylated genes. A combination of epigenetic modulators may be used to increase chromatin accessibility of the pancreatic transcription factors, thus promoting the efficiency of the developmental process.
Sex at the interface: the origin and impact of sex differences in the developing human placenta
Authors: Braun Amy E. , Mitchel Olivia R. , Gonzalez Tania L. , Sun Tianyanxin , Flowers Amy E. , Pisarska Margareta D. , Winn Virginia D.
Published: September 2022

The fetal placenta is a source of hormones and immune factors that play a vital role in maintaining pregnancy and facilitating fetal growth. Cells in this extraembryonic compartment match the chromosomal sex of the embryo itself. Sex differences have been observed in common gestational pathologies, highlighting the importance of maternal immune tolerance to the fetal compartment. Over the past decade, several studies examining placentas from term pregnancies have revealed widespread sex differences in hormone signaling, immune signaling, and metabolic functions. Given the rapid and dynamic development of the human placenta, sex differences that exist at term (37–42 weeks gestation) are unlikely to align precisely with those present at earlier stages when the fetal–maternal interface is being formed and the foundations of a healthy or diseased pregnancy are established. While fetal sex as a variable is often left unreported in studies performing transcriptomic profiling of the first-trimester human placenta, four recent studies have specifically examined fetal sex in early human placental development. In this review, we discuss the findings from these publications and consider the evidence for the genetic, hormonal, and immune mechanisms that are theorized to account for sex differences in early human placenta. We also highlight the cellular and molecular processes that are most likely to be impacted by fetal sex and the evolutionary pressures that may have given rise to these differences. With growing recognition of the fetal origins of health and disease, it is important to shed light on sex differences in early prenatal development, as these observations may unlock insight into the foundations of sex-biased pathologies that emerge later in life.
Bioprospecting endophytic fungi for antifeedants and larvicides and their enhancement by gamma irradiation
Authors: Hazaa Magdia A. , Shebl Magdy M. , El-Sayed El-Sayed R. , Mahmoud Samar R. , Khattab Abeer A. , Amer Mahmoud M.
Published: September 2022

The search and discovery of new natural products with antifeedant and larvicidal potentials to mitigate harmful insects are scientific pressing issues in the modern agriculture. In this paper, the antifeedant and larvicidal potentials of 69 fungal isolates were screened against the Egyptian cotton leafworm Spodoptera littoralis. A total of 17 isolates showed the insecticidal potentials with three promising isolates. These strains were Aspergillus sydowii, Lasiodiplodia theobromae, and Aspergillus flavus isolated from Ricinus communis (bark), Terminalia arjuna (Bark), and Psidium guajava (twigs), respectively. The effect of gamma irradiation on the antifeedant and larvicidal activities of the three strains was investigated. Exposure of the fungal spores to 1000 Gy of gamma rays significantly intensified both the antifeedant and larvicidal potentials. To identify compounds responsible for these activities, extracts of the three strains were fractionated by thin layer chromatography. The nature of the separated compounds namely, Penitrem A, 1, 3, 5, 8- tetramethyl- 4, 6-diethyl- 7- [2- (methoxycarbonyl)ethyl] porphyrin (from A. sydowii), Penitrem A, 2, 7, 12, 17-Tetramethyl-3, 5:8, 10:13, 15:18, 20-tetrakis (2,2-dimethylpropano) porphyrin (from A. flavus), N,N-Diethyl-3-nitrobenzamide, and Diisooctyl-phthalate (from L. theobromae) were studied by GC-MS analysis. These findings recommend endophytic fungi as promising sources of novel natural compounds to mitigate harmful insects.
Comparison of semi-supervised deep learning algorithms for audio classification
Authors: Cances Léo , Labbé Etienne , Pellegrini Thomas
Published: September 2022

In this article, we adapted five recent SSL methods to the task of audio classification. The first two methods, namely Deep Co-Training (DCT) and Mean Teacher (MT), involve two collaborative neural networks. The three other algorithms, called MixMatch (MM), ReMixMatch (RMM), and FixMatch (FM), are single-model methods that rely primarily on data augmentation strategies. Using the Wide-ResNet-28-2 architecture in all our experiments, 10% of labeled data and the remaining 90% as unlabeled data for training, we first compare the error rates of the five methods on three standard benchmark audio datasets: Environmental Sound Classification (ESC-10), UrbanSound8K (UBS8K), and Google Speech Commands (GSC). In all but one cases, MM, RMM, and FM outperformed MT and DCT significantly, MM and RMM being the best methods in most experiments. On UBS8K and GSC, MM achieved 18.02% and 3.25% error rate (ER), respectively, outperforming models trained with 100% of the available labeled data, which reached 23.29% and 4.94%, respectively. RMM achieved the best results on ESC-10 (12.00% ER), followed by FM which reached 13.33%. Second, we explored adding the mixup augmentation, used in MM and RMM, to DCT, MT, and FM. In almost all cases, mixup brought consistent gains. For instance, on GSC, FM reached 4.44% and 3.31% ER without and with mixup. Our PyTorch code will be made available upon paper acceptance at https://github.com/Labbeti/SSLH.
CLQLMRS: improving cache locality in MapReduce job scheduling using Q-learning
Authors: Ghazali Rana , Adabi Sahar , Rezaee Ali , Down Douglas G. , Movaghar Ali
Published: September 2022

Scheduling of MapReduce jobs is an integral part of Hadoop and effective job scheduling has a direct impact on Hadoop performance. Data locality is one of the most important factors to be considered in order to improve efficiency, as it affects data transmission through the system. A number of researchers have suggested approaches for improving data locality, but few have considered cache locality. In this paper, we present a state-of-the-art job scheduler, CLQLMRS (Cache Locality with Q-Learning in MapReduce Scheduler) for improving both data locality and cache locality using reinforcement learning. The proposed algorithm is evaluated by various experiments in a heterogeneous environment. Experimental results show significantly decreased execution time compared with FIFO, Delay, and the Adaptive Cache Local scheduler.
Prevalence of adequate postnatal care and associated factors in Rwanda: evidence from the Rwanda demographic health survey 2020
Authors: Kawuki Joseph , Gatasi Ghislaine , Sserwanja Quraish
Published: September 2022

Background

Although quality postnatal care (PNC) is a known significant intervention for curbing maternal and newborn morbidity and mortality, it is underutilized in most developing countries including Rwanda. Thus, it is crucial to identify factors that facilitate or occlude receipt of adequate PNC. This study aimed at assessing the prevalence of adequate PNC content and the associated factors in Rwanda.

Methods

We used weighted data from the Rwanda Demographic and Health Survey (RDHS) of 2020, comprising of 4456 women aged 15–49 years, who were selected using multistage sampling. Adequate PNC was considered if a woman had received all of the five components; having the cord examined, temperature of the baby measured, counselling on newborn danger signs, counselling on breastfeeding and having an observed breastfeeding session. We, then, conducted multivariable logistic regression to explore the associated factors, using SPSS version 25.

Results

Out of the 4456 women, 1974 (44.3, 95% confidence interval (CI): 43.0–45.9) had received all the PNC components. Having no radio exposure (adjusted odds ratio (AOR) =1.41, 95% CI: 1.18–1.68), visited by a fieldworker (AOR = 1.35, 95% CI: 1.16–1.57), no big problem with distance to a health facility (AOR = 1.50, 95% CI:1.24–1.81), and residing in the Southern region (AOR = 1.75, 95% CI: 1.42–2.15) were associated with higher odds of adequate PNC compared to their respective counterparts. However, having no exposure to newspapers/magazines (AOR = 0.74, 95% CI: 0.61–0.89), parity of less than 2 (AOR = 0.67, 95% CI: 0.51–0.86), being a working mother (AOR = 0.73, 95% CI: 0.62–0.85), no big problem with permission to seek healthcare (AOR = 0.54, 95% CI: 0.36–0.82), antenatal care (ANC) frequency of less than 4 times (AOR = 0.79, 95% CI: 0.62–0.85), inadequate ANC quality (AOR = 0.56, 95% CI: 0.46–0.68), and getting ANC in a public facility (AOR = 0.57, 95% CI: 0.38–0.85) were associated with lower odds of adequate PNC.

Conclusions

Less than half of the mothers in Rwanda had received adequate PNC, and this was associated with various factors. The results, thus, suggested context-specific evidence for consideration when rethinking policies to improve adequate PNC, including a need for intensified PNC education and counselling during ANC visits, continued medical education and training of PNC providers, and strengthening of maternal leave policies for working mothers.
Willingness to share information for energy efficiency: exploring differences and drivers across the Nordic countries
Authors: Reyes Joseph Anthony L.
Published: September 2022

Background

There is growing attention and policy debate about the sharing of personal information that the modernization of electricity grids requires. This is particularly important for big data management in smart grids that needs access to data generated and sent through devices such as smart meters. Using the Nordic Countries as a case study, this study investigates the willingness of people to share personal information for energy efficiency. The study builds upon data from the Eurobarometer survey and binary logistic regressions.

Results

Nordic countries exhibit a higher willingness to share personal information compared to the rest of the EU countries. However, despite high levels of concern for climate change and other pro-environmental attitudes found overall among Europeans, the willingness to share personal information is not as prevalent and is still mainly shaped by socio-demographic features such as gender and age. Key predictors also included climate change perception and congruence of citizen engagement with environmentally friendly behaviors. Several contextual and market-specific issues framing these findings are discussed (e.g., trust, energy use).

Conclusions

Even when high levels of pro-environmental attitudes in certain countries are found, let alone the Nordics, this does not mean people are willing to share personal information that would support pro-environmental energy efficiency behaviors and policies.
Cross-sectional study on the association of periodontitis with arterial hypertension in the Hamburg City Health Study
Authors: Könnecke Henrieke , Schnabel Renate B. , Walther Carolin , Lamprecht Ragna , Heydecke Guido , Seedorf Udo , Jagodzinski Annika , Borof Katrin , Zeller Tanja , Beikler Thomas , Smeets Ralf , Gosau Martin , Behrendt Christian-Alexander , Wenzel Ulrich , Börschel Christin S. , Karakas Mahir , Blankenberg Stefan , Aarabi Ghazal
Published: September 2022

Aim

Aim of this study was to investigate the association between periodontitis and arterial hypertension, both of which show correlations with classical cardiovascular risk factors and inflammatory activity.

Materials and methods

A cross-sectional analysis of data from a large population-based health survey (the Hamburg City Health Study, HCHS) including 5934 participants with complete periodontal examination and blood pressure data, of whom 5735 had medical records regarding anti-hypertensive medication, was performed. Probing depths, gingival recessions, bleeding on probing (BOP), dental plaque, and decayed-missing-filled teeth (DMFT) indices were recorded as measures of oral health. Clinical attachment loss (CAL) per tooth was calculated and periodontitis was staged into three groups (no/mild, moderate, severe). Arterial hypertension was diagnosed based on the participants’ medication history and systolic and diastolic blood pressure values. Logistic regression models were constructed accounting for a set of potential confounders (age, sex, smoking, body mass index (BMI), diabetes, educational level, alcohol intake) and high sensitivity-C-reactive protein (hsCRP).

Results

The odds of arterial hypertension increased significantly along with periodontitis severity (OR for severe periodontitis: 2.19; 95% CI 1.85–2.59; p < 0.001; OR for moderate periodontitis: 1.65; 95% CI 1.45–1.87; p < 0.001). Participants with moderate or severe periodontitis also had significantly higher age- and sex-adjusted odds of arterial hypertension, which was slightly weakened when additionally adjusted for BMI, diabetes, smoking, educational level, and alcohol intake (OR for severe PD: 1.28, 95% CI 1.04–1.59, p = 0.02; OR for moderate PD: 1.30, 95% CI 1.11–1.52, p = 0.001). The fraction of participants with undertreated hypertension (untreated and poorly controlled hypertension) was considerably larger in participants with severe periodontitis than in those with no/mild periodontitis (50.1% vs. 37.4% for no/mild periodontitis).

Conclusions

The study shows an association between periodontitis and arterial hypertension that is independent of age, sex, diabetes, BMI, smoking, educational level, and alcohol intake. In addition, undertreatment of hypertension was more common in people with severe periodontitis compared with periodontally more healthy people.
Ethical challenges in mass drug administration for reducing childhood mortality: a qualitative study
Authors: Alasmar Ahmed , Kong Alex C. , So Anthony D. , DeCamp Matthew
Published: September 2022

Background

Mass drug administration (MDA) of medications to entire at-risk communities or populations has shown promise in the control and elimination of global infectious diseases. MDA of the broad-spectrum antibiotic azithromycin has demonstrated the potential to reduce childhood mortality in children at risk of premature death in some global settings. However, MDA of antibiotics raises complex ethical challenges, including weighing near-term benefits against longer-term risks—particularly the development of antimicrobial resistance that could diminish antibiotic effectiveness for current or future generations. The aim of this study was to understand how key actors involved in MDA perceive the ethical challenges of MDA.

Methods

We conducted 35 semi-structured interviews from December 2020–February 2022 with investigators, funders, bioethicists, research ethics committee members, industry representatives, and others from both high-income countries (HICs) and low- and middle-income countries (LMICs). Interview participants were identified via one of seven MDA studies purposively chosen to represent diversity in terms of use of the antibiotic azithromycin; use of a primary mortality endpoint; and whether the study occurred in a high child mortality country. Data were analyzed using constructivist grounded theory methodology.

Results

The most frequently discussed ethical challenges related to meaningful community engagement, how to weigh risks and benefits, and the need to target MDA We developed a concept map of how participants considered ethical issues in MDA for child mortality; it emphasizes MDA’s place alongside other public health interventions, empowerment, and equity. Concerns over an ethical double standard in weighing risks and benefits emerged as a unifying theme, albeit one that participants interpreted in radically different ways. Some thought MDA for reducing child mortality was ethically obligatory; others suggested it was impermissible.

Conclusions

Ethical challenges raised by MDA of antibiotics for childhood mortality—which span socio-cultural issues, the environment, and effects on future generations—require consideration beyond traditional clinical trial review. The appropriate role of MDA also requires attention to concerns over ethical double standards and power dynamics in global health that affect how we view antibiotic use in HICs versus LMICs. Our findings suggest the need to develop additional, comprehensive guidance on managing ethical challenges in MDA.

Graphical Abstract
Phosphorylation of β-catenin at Serine552 correlates with invasion and recurrence of non-functioning pituitary neuroendocrine tumours
Authors: Rai Ashutosh , Yelamanchi Soujanya D. , Radotra Bishan D. , Gupta Sunil K. , Mukherjee Kanchan K. , Tripathi Manjul , Chhabra Rajesh , Ahuja Chirag K. , Kumar Narendra , Pandey Akhilesh , Korbonits Márta , Dutta Pinaki , Gaston-Massuet Carles
Published: September 2022

Non-functioning pituitary tumours (NF-PitNETs) are common intracranial benign neoplasms that can exhibit aggressive behaviour by invading neighbouring structures and, in some cases, have multiple recurrences. Despite resulting in severe co-morbidities, no predictive biomarkers of recurrence have been identified for NF-PitNETs. In this study we have used high-throughput mass spectrometry-based analysis to examine the phosphorylation pattern of different subsets of NF-PitNETs. Based on histopathological, radiological, surgical and clinical features, we have grouped NF-PitNETs into non-invasive, invasive, and recurrent disease groups. Tumour recurrence was determined based on regular clinical and radiological data of patients for a mean follow-up of 10 years (SD ± 5.4 years). Phosphoproteomic analyses identified a unique phosphopeptide enrichment pattern which correlates with disease recurrence. Candidate phosphorylated proteins were validated in a large cohort of NF-PitNET patients by western blot and immunohistochemistry. We identified a cluster of 22 phosphopeptides upregulated in recurrent NF-PitNETs compared to non-invasive and invasive subgroups. We reveal significant phosphorylation of the β-catenin at Ser552 in recurrent and invasive NF-PitNETs, compared to non-invasive/non-recurrent NF-PitNET subgroup. Moreover, β-catenin pSer552 correlates with the recurrence free survival among 200 patients with NF-PitNET. Together, our results suggest that the phosphorylation status of β-catenin at Ser552 could act as potential biomarker of tumour recurrence in NF-PitNETs.
Histopathological effects of methomyl and crude extracts of Jatropha curcas against the terrestrial snail, Monacha obstructa (Gastropoda:Hygromiidae)
Authors: Ibrahim Hesham Ahmed Metwaly , El-Mesalamy Anas Farag , Baghdadi Saudi Abd El-Wahab Sayed , Elhanbaly Ruwaida
Published: September 2022

Background

The negative effect of over-reliance on the use of synthetic pesticides have led to the search for natural alternatives to pest control. This study was designed to evaluate the toxicity effect of the crude plant extracts of Jatropha (Jatropha curcas Linn.) seeds in comparison with methomyl on some histopathological changes of the terrestrial snail species Monacha obstructa (Pfeiffer, 1842). The toxicity effect of methomyl and crude extracts of ethanol and acetone extracts of Jatropha curcas seeds were determined on some histological changes of the land snail, Monacha obstructa at four concentrations using the contact technique under laboratory conditions.

Results

The results revealed that the crude extracts of Jatropha exhibited obvious adequate effects compared with methomyl against M. obstructa land snails. The highest toxicity effects were obtained by methomyl followed by the ethanolic extract of Jatropha and hexane extract of Jatropha. The histopathological effect of LC50 of Jatropha crude extract and methomyl on the digestive gland and foot tissues were examined in the land snails M. obstructa. The treated snails showed several histological changes in the digestive gland and foot compared with the control group snails. The histological examinations of the digestive tubules included destroyed and detached in the outer layer covering digestive tubules. In addition, marked increase in the width most of the digestive tubules lumen. The intertubular connective tissue between the digestive tubules showed great destruction, while the foot of treated snails showed rupture of the epithelium covering the foot and desquamation of the epithelium. We also observed the presence of areas of connective tissue necrosis and destruction of the muscular tissue.

Conclusions

It has been found that extracts of Jatropha seeds have a toxic activity that caused histopathological damage that led to the death of land snails, and thus it can be recommended as a source for the development of molluscicides.

Graphical Abstract
Effects of pyroligneous acid as silage additive on fermentation quality and bacterial community structure of waste sugarcane tops
Authors: Wu Shuo , Wang Cheng , Chen Dandan , Zhou Wei , Chen Xiaoyang , Wang Mingya , Zhang Qing
Published: September 2022

This article intends to improve the recycling of waste sugarcane (Saccharum officinarum) tops and the value-added utilization of pyroligneous acid. Fresh sugarcane tops can be used by ruminants, but they are prone to dehydration and mildew during storage, reducing their feeding value. Pyroligneous acid, a by-product in the process of making biochar, has good antibacterial effects. Adding pyroligneous acid to sugarcane tops for silage fermentation may be an effective way to promote the recycling of sugarcane tops. Thus, the fermentation quality and bacterial community of sugarcane tops ensiled with or without 1–2% pyroligneous acid for 5, 10, 20, or 100 days were investigated. Results showed that pyroligneous acid increased the acetic acid content and reduced ammonia-N concentration, and numbers of coliform bacteria and molds in sugarcane tops silages. On the other hand, the addition of pyroligneous acid decreased the diversity of bacteria in sugarcane-top silage. Pyroligneous acid decreased Firmicutes and Leuconostoc relative abundances while increasing Lactobacillus relative abundances. Fermentation was also limited by the addition of pyroligneous acid, which reduced metabolic activities during ensiling.

Graphical abstract
Kalmag: a high spatio-temporal model of the geomagnetic field
Authors: Baerenzung Julien , Holschneider Matthias , Saynisch-Wagner Jan , Thomas Maik
Published: September 2022

We present the extension of the Kalmag model, proposed as a candidate for IGRF-13, to the twentieth century. The dataset serving its derivation has been complemented by new measurements coming from satellites, ground-based observatories and land, marine and airborne surveys. As its predecessor, this version is derived from a combination of a Kalman filter and a smoothing algorithm, providing mean models and associated uncertainties. These quantities permit a precise estimation of locations where mean solutions can be considered as reliable or not. The temporal resolution of the core field and the secular variation was set to 0.1 year over the 122 years the model is spanning. Nevertheless, it can be shown through ensembles a posteriori sampled, that this resolution can be effectively achieved only by a limited amount of spatial scales and during certain time periods. Unsurprisingly, highest accuracy in both space and time of the core field and the secular variation is achieved during the CHAMP and Swarm era. In this version of Kalmag, a particular effort was made for resolving the small-scale lithospheric field. Under specific statistical assumptions, the latter was modeled up to spherical harmonic degree and order 1000, and signal from both satellite and survey measurements contributed to its development. External and induced fields were jointly estimated with the rest of the model. We show that their large scales could be accurately extracted from direct measurements whenever the latter exhibit a sufficiently high temporal coverage. Temporally resolving these fields down to 3 hours during the CHAMP and Swarm missions, gave us access to the link between induced and magnetospheric fields. In particular, the period dependence of the driving signal on the induced one could be directly observed. The model is available through various physical and statistical quantities on a dedicated website at https://ionocovar.agnld.uni-potsdam.de/Kalmag/.

Graphical abstract
Epilepsy seizure prediction with few-shot learning method
Authors: Nazari Jamal , Motie Nasrabadi Ali , Menhaj Mohammad Bagher , Raiesdana Somayeh
Published: September 2022

Epileptic seizures prediction and timely alarms allow the patient to take effective and preventive actions. In this paper, a convolutional neural network (CNN) is proposed to diagnose the preictal period. Our goal is for those epileptic patients in whom seizures occur late and it is very challenging to record the preictal signal for them. In the previous works, generalized methods were inevitably used for this group of patients which were not very accurate. Our approach to solve this problem is to provide a few-shot learning method. This method, having the previous knowledge, is trained with only a small number of samples, learns new tasks and reduces the efforts to collect more data. Evaluation results for three patients from the CHB–MIT database, for a 10-min seizure prediction horizon (SPH) and a 20-min seizure occurrence period (SOP), averaged sensitivity of 95.70% and a false prediction rate (FPR) of 0.057/h and for the 5-min prediction horizon and the 25-min seizure occurrence period averaged sensitivity of 98.52% and a false prediction rate of (FPR) of 0.045/h. The proposed few-shot learning method, based on previous knowledge gained from the generalizable method, is regulated with a few new patient samples for the patient. Our results show that the accuracy obtained in this method is higher than the generalizable methods.
RNeuMark: A Riemannian EEG Analysis Framework for Neuromarketing
Authors: Georgiadis Kostas , Kalaganis Fotis P. , Oikonomou Vangelis P. , Nikolopoulos Spiros , Laskaris Nikos A. , Kompatsiaris Ioannis
Published: September 2022

Neuromarketing exploits neuroimaging techniques so as to reinforce the predictive power of conventional marketing tools, like questionnaires and focus groups. Electroencephalography (EEG) is the most commonly encountered neuroimaging technique due to its non-invasiveness, low-cost, and its very recent embedding in wearable devices. The transcription of brainwave patterns to consumer attitude is supported by various signal descriptors, while the quest for profitable novel ways is still an open research question. Here, we suggest the use of sample covariance matrices as alternative descriptors, that encapsulate the coordinated neural activity from distinct brain areas, and the adoption of Riemannian geometry for their handling. We first establish the suitability of Riemannian approach for neuromarketing-related problems and then suggest a relevant decoding scheme for predicting consumers’ choices (e.g., willing to buy or not a specific product). Since the decision-making process involves the concurrent interaction of various cognitive processes and consequently of distinct brain rhythms, the proposed decoder takes the form of an ensemble classifier that builds upon a multi-view perspective, with each view dedicated to a specific frequency band. Adopting a standard machine learning procedure, and using a set of trials (training data) in conjunction with the associated behavior labels (“buy”/ “not buy”), we train a battery of classifiers accordingly. Each classifier is designed to operate in the space recovered from the inter-trial distances of SCMs and to cast a rhythm-depended decision that is eventually combined with the predictions of the rest ones. The demonstration and evaluation of the proposed approach are performed in 2 neuromarketing-related datasets of different nature. The first is employed to showcase the potential of the suggested descriptor, while the second to showcase the decoder’s superiority against popular alternatives in the field.
Case report of congenital methemoglobinemia: an uncommon cause of neonatal cyanosis
Authors: Lyle Allison N. J. , Spurr Rebecca , Kirkey Danielle , Albert Catherine M. , Billimoria Zeenia , Perez Jose , Puia-Dumitrescu Mihai
Published: September 2022

Background

Methemoglobinemia can be an acquired or congenital condition. The acquired form occurs from exposure to oxidative agents. Congenital methemoglobinemia is a rare and potentially life-threatening cause of cyanosis in newborns that can be caused by either cytochrome B5reductase or hemoglobin variants known as Hemoglobin M.

Case presentation

A term male infant developed cyanosis and hypoxia shortly after birth after an uncomplicated pregnancy, with oxygen saturations persistently 70–80% despite 1.0 FiO2 and respiratory support of CPAP+ 6 cm H2O. Pre- and post-ductal saturations were equal and remained below 85%. Initial radiographic and echography imaging was normal. Capillary blood gas values were reassuring with normal pH and an elevated pO2. Investigations to rule out hemolysis and end-organ dysfunction were within acceptable range. Given the absence of clear cardiac or pulmonary etiology of persistent cyanosis, hematologic causes such as methemoglobinemia were explored. No family history was available at the time of transfer to our institution. Unconjugated hyperbilirubinemia > 5 mg/dL (442 μmol/L) interfered with laboratory equipment measurement, making accurate methemoglobin levels unattainable despite multiple attempts. Initial treatment with methylene blue or ascorbic acid was considered. However, upon arrival of the presumed biological father, a thorough history revealed an extensive paternal family history of neonatal cyanosis due to a rare mutation resulting in a hemoglobin M variant. Given this new information, hematology recommended supportive care as well as further testing to confirm the diagnosis of congenital methemoglobinopathy. Whole genome sequencing revealed a likely pathogenic variation in hemoglobin. The neonate was discharged home at 2 weeks of age on full oral feeds with 0.25 L/min nasal cannula as respiratory support, with close outpatient follow-up. By 5 weeks of age, he was weaned off respiratory support.

Conclusion

Congenital methemoglobinemia should be considered in the differential diagnosis for newborns with persistent hypoxemia despite normal imaging and laboratory values. Accurate quantification of methemoglobin concentrations is challenging in neonates due to the presence of other substances that absorb light at similar wavelengths, including HbF, bilirubin, and lipids.
Recalling fake news during real news corrections can impair or enhance memory updating: the role of recollection-based retrieval
Authors: Kemp Paige L. , Alexander Timothy R. , Wahlheim Christopher N.
Published: September 2022

Fake news can impair memory leading to societal controversies such as COVID-19 vaccine efficacy. The pernicious influence of fake news is clear when ineffective corrections leave memories outdated. A key theoretical issue is whether people should recall fake news while reading corrections with contradictory details. The familiarity backfire view proposes that recalling fake news increases its familiarity, leading to interference. However, the integrative encoding view proposes that recalling fake news promotes co-activation and binding of contradictory details, leading to facilitation. Two experiments examined if one theory better accounts for memory updating after participants recalled actual fake news details when reading headlines that corrected misinformation. In Phase 1, participants read real and fake news headlines of unclear veracity taken from various internet sources. In Phase 2, participants read real news headlines that reaffirmed real news and corrected fake news from Phase 1. When they detected that Phase 2 real news corrected fake news, they attempted to recall Phase 1 fake news. In Phase 3, participants first recalled real news details. When they remembered that those details were corrections from Phase 2, they attempted to recall fake news from Phase 1. Recalling fake news when noticing corrections in Phase 2 led to better memory for real news in Phase 3 when fake news was recalled again and worse memory for real news in Phase 3 when fake news was not recalled again. Both views explain part of the memory differences associated with recalling fake news during corrections, but only when considering whether people recollected that fake news had been corrected.
Pseudopotential-based discrete unified gas kinetic scheme for modeling multiphase fluid flows
Authors: Yang Zeren , Liu Sha , Zhuo Congshan , Zhong Chengwen
Published: September 2022

To directly incorporate the intermolecular interaction effects into the discrete unified gas-kinetic scheme (DUGKS) for simulations of multiphase fluid flow, we developed a pseudopotential-based DUGKS by coupling the pseudopotential model that mimics the intermolecular interaction into DUGKS. Due to the flux reconstruction procedure, additional terms that break the isotropic requirements of the pseudopotential model will be introduced. To eliminate the influences of nonisotropic terms, the expression of equilibrium distribution functions is reformulated in a moment-based form. With the isotropy-preserving parameter appropriately tuned, the nonisotropic effects can be properly canceled out. The fundamental capabilities are validated by the flat interface test and the quiescent droplet test. It has been proved that the proposed pseudopotential-based DUGKS managed to produce and maintain isotropic interfaces. The isotropy-preserving property of pseudopotential-based DUGKS in transient conditions is further confirmed by the spinodal decomposition. Stability superiority of the pseudopotential-based DUGKS over the lattice Boltzmann method is also demonstrated by predicting the coexistence densities complying with the van der Waals equation of state. By directly incorporating the intermolecular interactions, the pseudopotential-based DUGKS offers a mesoscopic perspective of understanding multiphase behaviors, which could help gain fresh insights into multiphase fluid flow.