bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges and care strategies associated with the admission to nursing homes in Germany: a scoping review
Authors: Skudlik Stefanie , Hirt Julian , Döringer Tobias , Thalhammer Regina , Lüftl Katharina , Prodinger Birgit , Müller Martin
Published: January 2023

Background

The admission to a nursing home is a critical life-event for affected persons as well as their families. Admission related processes are lacking adequate participation of older people and their families. To improve transitions to nursing homes, context- and country-specific knowledge about the current practice is needed. Hence, our aim was to summarize available evidence on challenges and care strategies associated with the admission to nursing homes in Germany.

Methods

We conducted a scoping review and searched eight major international and German-specific electronic databases for journal articles and grey literature published in German or English language since 1995. Further inclusion criteria were focus on challenges or care strategies in the context of nursing home admissions of older persons and comprehensive and replicable information on methods and results. Posters, only-abstract publications and articles dealing with mixed populations including younger adults were excluded. Challenges and care strategies were identified and analysed by structured content analysis using the TRANSCIT model.

Results

Twelve studies of 1,384 records were finally included. Among those, seven were qualitative studies, three quantitative observational studies and two mixed methods studies. As major challenges neglected participation of older people, psychosocial burden among family caregivers, inadequate professional cooperation and a lack of shared decision-making and evidence-based practice were identified. Identified care strategies included strengthening shared decision-making and evidence-based practice, improvement in professional cooperation, introduction of specialized transitional care staff and enabling participation for older people.

Conclusion

Although the process of nursing home admission is considered challenging and tends to neglect the needs of older people, little research is available for the German health care system. The perspective of the older people seems to be underrepresented, as most of the studies focused on caregivers and health professionals. Reported care strategies addressed important challenges, however, these were not developed and evaluated in a comprehensive and systematic way. Future research is needed to examine perspectives of all the involved groups to gain a comprehensive picture of the needs and challenges. Interventions based on existing care strategies should be systematically developed and evaluated to provide the basis of adequate support for older persons and their informal caregivers.
Prolonged anesthesia induces neuroinflammation and complement-mediated microglial synaptic elimination involved in neurocognitive dysfunction and anxiety-like behaviors
Authors: Xu Feng , Han Linlin , Wang Yafeng , Deng Daling , Ding Yuanyuan , Zhao Shuai , Zhang Qingtong , Ma Lulin , Chen Xiangdong
Published: January 2023

Background

Perioperative neurocognitive disorders (PND) with a high incidence frequently occur in elderly surgical patients closely associated with prolonged anesthesia-induced neurotoxicity. The neuromorphopathological underpinnings of anesthesia-induced neurotoxicity have remained elusive.

Methods

Prolonged anesthesia with sevoflurane was used to establish the sevoflurane-induced neurotoxicity (SIN) animal model. Morris water maze, elevated plus maze, and open field test were employed to track SIN rats’ cognitive behavior and anxiety-like behaviors. We investigated the neuropathological basis of SIN through techniques such as transcriptomic, electrophysiology, molecular biology, scanning electron microscope, Golgi staining, TUNEL assay, and morphological analysis. Our work further clarifies the pathological mechanism of SIN by depleting microglia, inhibiting neuroinflammation, and C1q neutralization.

Results

This study shows that prolonged anesthesia triggers activation of the NF-κB inflammatory pathway, neuroinflammation, inhibition of neuronal excitability, cognitive dysfunction, and anxiety-like behaviors. RNA sequencing found that genes of different types of synapses were downregulated after prolonged anesthesia. Microglial migration, activation, and phagocytosis were enhanced. Microglial morphological alterations were also observed. C1qa, the initiator of the complement cascade, and C3 were increased, and C1qa tagging synapses were also elevated. Then, we found that the “Eat Me” complement pathway mediated microglial synaptic engulfment in the hippocampus after prolonged anesthesia. Afterward, synapses were remarkably lost in the hippocampus. Furthermore, dendritic spines were reduced, and their genes were also downregulated. Depleting microglia ameliorated the activation of neuroinflammation and complement and rescued synaptic loss, cognitive dysfunction, and anxiety-like behaviors. When neuroinflammatory inhibition or C1q neutralization occurred, complement was also decreased, and synaptic elimination was interrupted.

Conclusions

These findings illustrated that prolonged anesthesia triggered neuroinflammation and complement-mediated microglial synaptic engulfment that pathologically caused synaptic elimination in SIN. We have demonstrated the neuromorphopathological underpinnings of SIN, which have direct therapeutic relevance for PND patients.
Development of a workflow for the detection of vancomycin-resistant Enterococcus faecium and Enterococcus faecalis from rectal swabs using the spectra VRE medium
Authors: Kling Kendall , Rios Javier , Dirnberger Laura , Polanco Wanda , Fritz Kevin , Malczynski Michael , Zembower Teresa , Qi Chao
Published: January 2023

Background

Spectra™ VRE agar (Remel, Lenexa, KS) is a chromogenic agar that is FDA approved for screening patients for VRE colonization. The package insert recommends confirming isolates with identification and susceptibility testing, but confirming every culture delays time to result. Given the agar’s historic high specificity for E. faecium isolates, we theorized the agar could be utilized as a stand-alone screening to minimize reagents and time.

Aim

Our laboratory sought to develop a workflow to optimize the use of the medium.

Methods

We plated 3,815 rectal swabs to the Spectra VRE agar and compared results to traditional identification and susceptibility testing.

Results

Dark blue or purple colonies on the agar demonstrated a sensitivity of 98% and specificity of 85% for detection of VRE faecium, but light blue colonies were significantly less specific for E. faecalis.

Conclusions

We streamlined our workflow to accept dark blue or purple colonies as VRE faecium and plan to perform additional testing only on light blue colonies. Interestingly, higher quantity of growth increased the accuracy of the agar. In the future, growth quantity may be used to further streamline the workflow once more data is obtained.
Breastfeeding in the first hour of life in Brazilian private hospitals participating in a quality-of-care improvement project
Authors: Alves Rachael de Vasconcelos , de Oliveira Maria Inês Couto , Domingues Rosa Maria Soares Madeira , Pereira Ana Paula Esteves , Leal Maria do Carmo
Published: January 2023

Background

The Baby-Friendly Hospital Initiative’s Step 4 recommends: “support mothers to start breastfeeding as soon as possible after birth”, thus contributing to the reduction of neonatal mortality. The objective of this study is to estimate the prevalence of breastfeeding in the first hour of life in private maternity hospitals participating in the “Adequate Childbirth Project”, a quality-of-care improvement project, and to analyze determinants of this outcome.

Methods

Secondary analysis of data collected by the cross-sectional evaluative “Healthy Birth Study”, conducted in 2017 in 12 maternity hospitals participating in the Adequate Childbirth Project, where 4800 mothers were interviewed, and hospital records were observed. Conditions that prevented breastfeeding at birth, such as maternal HIV-infection and newborns’ severe malformations, were excluded. Multiple logistic regression was performed according to a hierarchical theoretical model.

Results

The prevalence of breastfeeding in the first hour of life was 58% (CI 95% 56.6–59.5%). Lower maternal education (aOR 0.643; CI 95% 0.528–0.782), lower economic status (aOR 0.687; CI 95% 0.504–0.935), cesarean section delivery (ORa 0.649; CI 95% 0.529–0.797), preterm birth (aOR 0.660; CI 95% 0.460–0.948) and non-rooming-in at birth (aOR 0.669; CI 95% 0.559–0.800) were negatively associated with the outcome. Receiving information during prenatal care about the importance of breastfeeding at birth (aOR 2.585; CI 95% 2.102–3.179), being target of the quality-of-care improvement project (aOR 1.273; CI 95% 1.065–1.522), skin-to-skin contact at birth (aOR 2.127; CI 95% 1.791–2.525) and female newborn (aOR 1.194; CI 95% 1.008–1.415) were factors positively associated with the outcome.

Conclusions

The private maternities participating in the Healthy Birth Study showed a good prevalence of breastfeeding in the first hour of life, according to WHO parameters. Prenatal guidance on breastfeeding at birth, being target of the quality-of-care improvement project and skin-to-skin contact at birth contributed to breastfeeding in the first hour of life.
Gut microbiome and stages of diabetes in middle-aged adults: CARDIA microbiome study
Authors: Hu Yi-Han , Meyer Katie , Lulla Anju , Lewis Cora E. , Carnethon Mercedes R. , Schreiner Pamela J. , Sidney Stephen , Shikany James M. , Meirelles Osorio , Launer Lenore J.
Published: January 2023

Background

Animal and human studies suggest the gut microbiome is linked to diabetes but additional data are needed on the associations of the gut microbiome to specific diabetes characteristics. The aim of this study was to examine the associations of gut microbiome composition to insulin resistance [Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)], duration of diabetes, and 4 stages of diabetes [normoglycemia, pre-diabetes, and diabetes with (+) and without (−) medication for diabetes].

Methods

Data are from a sub-sample (n = 605) of Black and White participants from the 30-year follow-up exam of the prospectively followed community-based Coronary Artery Risk Development in Young Adults cohort (2015–2016; aged 48–60 years). Stool samples were collected and sequenced using the 16S ribosomal RNA method. Microbial measures included: α diversity (within-person), β diversity (between-person), and taxonomies. All analyses were adjusted for demographic, clinical, lifestyle factors, and use of relevant medications (full adjustment). Multivariate linear regression models were used to assess the association of diabetes characteristics with α diversity and genera abundance, while the association with β diversity was analyzed using permutational multivariate analysis of variance. Statistical significance was set top-value < 0.05 for α and β diversity analyses and to q-value < 0.1 for genera abundance analyses.

Results

There were 16.7% of participants with pre-diabetes, and 14.4% with diabetes (9% diabetes+) with median (interquartile range) diabetes duration of 5 (5–10) years. In the fully adjusted models, compared to those with no diabetes, longer diabetes duration and the diabetes + group had a lower α diversity. There were significant differences in β diversity across diabetes-related characteristics. A significantly reduced abundance of butyrate-producing genera was associated with higher HOMA-IR (ex.,AnaerostipesandLachnospiraceae_UCG.004), longer diabetes duration (ex.,AgathobacterandRuminococcus), and diabetes + (ex.,FaecalibacteriumandRomboutsia).

Conclusions

Our results suggest that an adverse alteration of gut microbiome composition is related to higher insulin resistance, longer diabetes duration, and is present in those persons with diabetes using medications. These diabetes-related characteristics were also associated with lower levels of certain butyrate-producing bacteria that produce health-promoting short‐chain fatty acids. Understanding the role of gut microbiota in glucose regulation may provide new strategies to reduce the burden of diabetes.
Towards the rate limit of heterologous biotechnological reactions in recombinant cyanobacteria
Authors: Barone Giovanni Davide , Hubáček Michal , Malihan-Yap Lenny , Grimm Hanna C. , Nikkanen Lauri , Pacheco Catarina C. , Tamagnini Paula , Allahverdiyeva Yagut , Kourist Robert
Published: January 2023

Background

Cyanobacteria have emerged as highly efficient organisms for the production of chemicals and biofuels. Yet, the productivity of the cell has been low for commercial application. Cyanobacterial photobiotransformations utilize photosynthetic electrons to form reducing equivalents, such as NADPH-to-fuel biocatalytic reactions. These photobiotransformations are a measure to which extent photosynthetic electrons can be deviated toward heterologous biotechnological processes, such as the production of biofuels. By expressing oxidoreductases, such as YqjM fromBacillus subtilisinSynechocystissp. PCC 6803, a high specific activity was obtained in the reduction of maleimides. Here, we investigated the possibility to accelerate the NAD(P)H-consuming redox reactions by addition of carbohydrates as exogenous carbon sources such as D-Glucose under light and darkness.

Results

A 1.7-fold increase of activity (150 µmol min−1gDCW−1) was observed upon addition of D-Glucose at an OD750 = 2.5 (DCW = 0.6 g L−1) in the biotransformation of 2-methylmaleimide. The stimulating effect of D-Glucose was also observed at higher cell densities in light and dark conditions as well as in the reduction of other substrates. No increase in both effective photosynthetic yields of Photosystem II and Photosystem I was found upon D-Glucose addition. However, we observed higher NAD(P)H fluorescence when D-Glucose was supplemented, suggesting increased glycolytic activity. Moreover, the system was scaled-up (working volume of 200 mL) in an internally illuminated Bubble Column Reactor exhibiting a 2.4-fold increase of specific activity under light-limited conditions.

Conclusions

Results show that under photoautotrophic conditions at a specific activity of 90 µmol min−1 gDCW−1, the ene-reductase YqjM inSynechocystissp. PCC 6803 is not NAD(P)H saturated, which is an indicator that an increase of the rates of heterologous electron consuming processes for catalysis and biofuel production will require funnelling further reducing power from the photosynthetic chain toward heterologous processes.
Afoxolaner (NexGard®) in pet snakes for the treatment and control of Ophionyssus natricis (Mesostigmata: Macronyssidae)
Authors: Mendoza-Roldan Jairo Alfonso , Napoli Ettore , Perles Livia , Marino Matteo , Spadola Filippo , Berny Philippe , España Bernadette , Brianti Emanuele , Beugnet Frederic , Otranto Domenico
Published: January 2023

Background

Ophionyssus natricisis the main species of mite that infests captive reptiles. High infestations may result in the host experiencing general discomfort and deleterious effects, even death. Moreover,O. natricisis an important vector of reptile vector-borne diseases and is considered to be the putative vector of theReptarenavirus,the causal agent of the inclusion body disease. Despite the cosmopolitan distribution ofO. natricisin captive reptiles, treatment options are limited. The aim of the present study was to assess the efficacy of afoxolaner (NexGard®; Boehringer Ingelheim, Ingelheim, Germany) in heavily infested, privately owned snakes, evaluate the prevalence of mites and drug availability in the plasma of treated snakes (pharmacokinetics) and perform a clinical examination of animals.

Methods

The study was conducted in two snake breeding facilities, where many snakes were infested with mites. Each animal was clinically examined and weighed, and mite infestations were assessed on the animals and in their enclosures (environment). Animals were treated with a dose of 2.5 mg afoxolaner per kilogram body weight (2.5 mg/kg) administered orally. All animals were examined pre-treatment (T0) and at various time points post-treatment (T1, 6 h; T2, 24 h; T3, 14 days; T4, 28 days). The collected mites were morphologically identified at the species level and the species identity also confirmed molecularly.

Results

Overall, 81 snakes from the two participating facilities (i.e. 70 from site 1 and 11 from site 2) were screened, and 31 (38.3%) snakes were found to have at least one mite. All mites were identified morphologically and molecularly asO. natricis. Lampropeltiswas the genus of snakes with highest number of infested individuals. Mites were found to be alive on snakes at T1, but at T2 only dead mites were observed, and at T3 and T4 mites were no longer present on the animals or in their environment. No side effects were observed in the treated snakes.

Conclusions

A single oral administration of afoxolaner at 2.5 mg/kg was a safe treatment for snakes and 100% effective for the eradication of naturalO. natricisinfestation without the need to treat the environment of the snake.

Graphical Abstract
Papyrus: a large-scale curated dataset aimed at bioactivity predictions
Authors: Béquignon O. J. M. , Bongers B. J. , Jespers W. , IJzerman A. P. , van der Water B. , van Westen G. J. P.
Published: January 2023

With the ongoing rapid growth of publicly available ligand–protein bioactivity data, there is a trove of valuable data that can be used to train a plethora of machine-learning algorithms. However, not all data is equal in terms of size and quality and a significant portion of researchers’ time is needed to adapt the data to their needs. On top of that, finding the right data for a research question can often be a challenge on its own. To meet these challenges, we have constructed the Papyrus dataset. Papyrus is comprised of around 60 million data points. This dataset contains multiple large publicly available datasets such as ChEMBL and ExCAPE-DB combined with several smaller datasets containing high-quality data. The aggregated data has been standardised and normalised in a manner that is suitable for machine learning. We show how data can be filtered in a variety of ways and also perform some examples of quantitative structure–activity relationship analyses and proteochemometric modelling. Our ambition is that this pruned data collection constitutes a benchmark set that can be used for constructing predictive models, while also providing an accessible data source for research.

Graphical Abstract
XSMILES: interactive visualization for molecules, SMILES and XAI attribution scores
Authors: Heberle Henry , Zhao Linlin , Schmidt Sebastian , Wolf Thomas , Heinrich Julian
Published: January 2023

Background

Explainable artificial intelligence (XAI) methods have shown increasing applicability in chemistry. In this context, visualization techniques can highlight regions of a molecule to reveal their influence over a predicted property. For this purpose, some XAI techniques calculate attribution scores associated with tokens of SMILES strings or with atoms of a molecule. While an association of a score with an atom can be directly visually represented on a molecule diagram, scores computed for SMILES non-atom tokens cannot. For instance, a substring [N+] contains 3 non-atom tokens, i.e., [, $$+$$
+
, and ], and their attributions, depending on the model, are not necessarily revealing an influence of the nitrogen atom over the predicted property; for that reason, it is not possible to represent the scores on a molecule diagram. Moreover, SMILES’s notation is complex, foregrounding the need for techniques to facilitate the analysis of explanations associated with their tokens.

Results

We propose XSMILES, an interactive visualization technique, to explore explainable artificial intelligence attributions scores and support the interpretation of SMILES. Users can input any type of score attributed to atom and non-atom tokens and visualize them on top of a 2D molecule diagram coordinated with a bar chart that represents a SMILES string. We demonstrate how attributions calculated for SMILES strings can be evaluated and better interpreted through interactivity with two use cases.

Conclusions

Data scientists can use XSMILES to understand their models’ behavior and compare multiple modeling approaches. The tool provides a set of parameters to adapt the visualization to users’ needs and it can be integrated into different platforms. We believe XSMILES can support data scientists to develop, improve, and communicate their models by making it easier to identify patterns and compare attributions through interactive exploratory visualization.
Multi-omics analysis of sarcospan overexpression in mdx skeletal muscle reveals compensatory remodeling of cytoskeleton-matrix interactions that promote mechanotransduction pathways
Authors: McCourt Jackie L. , Stearns-Reider Kristen M. , Mamsa Hafsa , Kannan Pranav , Afsharinia Mohammad Hossein , Shu Cynthia , Gibbs Elizabeth M. , Shin Kara M. , Kurmangaliyev Yerbol Z. , Schmitt Lauren R. , Hansen Kirk C. , Crosbie Rachelle H.
Published: January 2023

Background

The dystrophin-glycoprotein complex (DGC) is a critical adhesion complex of the muscle cell membrane, providing a mechanical link between the extracellular matrix (ECM) and the cortical cytoskeleton that stabilizes the sarcolemma during repeated muscle contractions. One integral component of the DGC is the transmembrane protein, sarcospan (SSPN). Overexpression of SSPN in the skeletal muscle of mdx mice (murine model of DMD) restores muscle fiber attachment to the ECM in part through an associated increase in utrophin and integrin adhesion complexes at the cell membrane, protecting the muscle from contraction-induced injury. In this study, we utilized transcriptomic and ECM protein-optimized proteomics data sets from wild-type, mdx, and mdx transgenic (mdxTG) skeletal muscle tissues to identify pathways and proteins driving the compensatory action of SSPN overexpression.

Methods

The tibialis anterior and quadriceps muscles were isolated from wild-type, mdx, and mdxTG mice and subjected to bulk RNA-Seq and global proteomics analysis using methods to enhance capture of ECM proteins. Data sets were further analyzed through the ingenuity pathway analysis (QIAGEN) and integrative gene set enrichment to identify candidate networks, signaling pathways, and upstream regulators.

Results

Through our multi-omics approach, we identified 3 classes of differentially expressed genes and proteins in mdxTG muscle, including those that were (1) unrestored (significantly different from wild type, but not from mdx), (2) restored (significantly different from mdx, but not from wild type), and (3) compensatory (significantly different from both wild type and mdx). We identified signaling pathways that may contribute to the rescue phenotype, most notably cytoskeleton and ECM organization pathways. ECM-optimized proteomics revealed an increased abundance of collagens II, V, and XI, along with β-spectrin in mdxTG samples. Using ingenuity pathway analysis, we identified upstream regulators that are computationally predicted to drive compensatory changes, revealing a possible mechanism of SSPN rescue through a rewiring of cell-ECM bidirectional communication. We found that SSPN overexpression results in upregulation of key signaling molecules associated with regulation of cytoskeleton organization and mechanotransduction, including Yap1, Sox9, Rho, RAC, and Wnt.

Conclusions

Our findings indicate that SSPN overexpression rescues dystrophin deficiency partially through mechanotransduction signaling cascades mediated through components of the ECM and the cortical cytoskeleton.
Economic burden on caregivers or parents with Down syndrome children—a systematic review protocol
Authors: Shetty Jyothi , Shetty Ankitha , Mundkur Suneel C. , Dinesh Tantri Keerthi , Pundir Prachi
Published: January 2023

Background

Financial burden is a common phenomenon, often noticed in the caregivers of children with Down syndrome. It echoes adverse effects on the caregiver’s mental and physical health. The economic burden covers direct healthcare costs, direct non-health-care costs, and indirect costs and is substantial for the family of a person with Down syndrome, as well as for society. Evidence, in this area, is necessary to reduce mental stress and promote financial well-being among caregivers.

Methods

In this review, quantitative studies that assess the economic burden on caregivers of children with Down syndrome will be considered. We will perform a systematic literature search conducted from the year 2000 to 2022 on electronic databases CINAHL, EBSCO, EMBASE, PubMed, Scopus, Web of Science, and EconLit. An additional gray literature search will be carried out. Two researchers will independently conduct the screening and data extraction and assess the risk of bias.

Discussions

The review attempts to methodically analyze the economic burden among caregivers of children with Down syndrome from the societal perspective and individual perspectives. The current study will provide an evidence base to researchers, academicians, and society in identifying need-based learning to caregivers, and the selection of appropriate therapies for children suffering from Down syndrome.

Systematic review registration

PROSPERO CRD42021265312
Mutations of TP53 and genes related to homologous recombination repair in breast cancer with germline BRCA1/2 mutations
Authors: Kim Jinyong , Jeong Kyeonghun , Jun Hyeji , Kim Kwangsoo , Bae Jeong Mo , Song Myung Geun , Yi Hanbaek , Park Songyi , Woo Go-un , Lee Dae-Won , Kim Tae-Yong , Lee Kyung-Hun , Im Seock-Ah
Published: January 2023

Background

Germline mutations of breast cancer susceptibility geneBRCA1andBRCA2(gBRCA1/2) are associated with elevated risk of breast cancer in young women in Asia. BRCA1 and BRCA2 proteins contribute to genomic stability through homologous recombination (HR)-mediated double-strand DNA break repair in cooperation with other HR-related proteins. In this study, we analyzed the targeted sequencing data of Korean breast cancer patients withgBRCA1/2mutations to investigate the alterations in HR-related genes and their clinical implications.

Materials and methods

Data of the breast cancer patients with pathogenicgBRCA1/2mutations and qualified targeted next-generation sequencing, SNUH FiRST cancer panel, were analyzed. Single nucleotide polymorphisms, small insertions, and deletions were analyzed with functional annotations using ANNOVAR. HR-related genes were defined asABL1, ATM, ATR, BARD1, BRCA1, BRCA2, CDKN1A, CDKN2A, CHEK1, CHEK2, FANCA, FANCD2, FANCG, FANCI, FANCL, KDR, MUTYH, PALB2, POLE, POLQ, RAD50, RAD51, RAD51D, RAD54L,andTP53. Mismatch-repair genes wereMLH1, MSH2, andMSH6. Clinical data were analyzed with cox proportional hazard models and survival analyses.

Results

Fifty-five Korean breast cancer patients with knowngBRCA1/2mutations and qualified targeted NGS data were analyzed. Ethnically distinct mutations ingBRCA1/2genes were noted, with higher frequencies of Val1833Ser (14.8%), Glu1210Arg (11.1%), and Tyr130Ter (11.1%) ingBRCA1and Arg2494Ter (25.0%) and Lys467Ter (14.3%) ingBRCA2.Considering subtypes,gBRCA1mutations were associated with triple-negative breast cancers (TNBC), whilegBRCA2mutations were more likely hormone receptor-positive breast cancers. At least one missense mutation of HR-related genes was observed in 44 cases (80.0%). The most frequently co-mutated gene wasTP53(38.1%). In patients withgBRCA1/2mutations, however, genetic variations ofTP53occurred in locations different from the known hotspots of those with sporadic breast cancers. The patients with bothgBRCA1/2andTP53mutations were more likely to have TNBC, high Ki-67 values, and increased genetic mutations, especially of HR-related genes. Survival benefit was observed in theTP53mutants of patients withgBRCA2mutations, compared to those withTP53wild types.

Conclusion

Our study showed genetic heterogeneity of breast cancer patients withgBRCA1andgBRCA2mutations in the Korean populations. Further studies on precision medicine are needed for tailored treatments of patients with genetic diversity among different ethnic groups.
MethylC-analyzer: a comprehensive downstream pipeline for the analysis of genome-wide DNA methylation
Authors: Lu Rita Jui-Hsien , Lin Pei-Yu , Yen Ming-Ren , Wu Bing-Heng , Chen Pao-Yang
Published: January 2023

DNA methylation is a crucial epigenetic modification involved in multiple biological processes and diseases. Current approaches for measuring genome-wide DNA methylation via bisulfite sequencing (BS-seq) include whole-genome bisulfite sequencing (WGBS), reduced representation bisulfite sequencing (RRBS), and enzymatic methyl-seq (EM-seq). The computational analysis tools available for BS-seq data include customized aligners for mapping bisulfite-converted reads and computational pipelines for downstream data analysis. Current post-alignment methylation tools are specialized for the interpretation of CG methylation, which is known to dominate mammalian genomes, however, non-CG methylation (CHG and CHH, where H refers to A, C, or T) is commonly observed in plants and fungi and is closely associated with gene regulation, transposon silencing, and plant development. Thus, we have developed a MethylC-analyzer to analyze and visualize post-alignment WGBS, RRBS, and EM-seq data focusing on CG. The tool is able to also analyze non-CG sites to enhance deciphering genomes of plants and fungi. By processing aligned data and gene location files, MethylC-analyzer generates a genome-wide view of methylation levels and methylation in user-specified genomic regions. The meta-plot, for example, allows the investigation of DNA methylation within specific genomic elements. Moreover, our tool identifies differentially methylated regions (DMRs) and investigates the enrichment of genomic features associated with variable methylation. MethylC-analyzer functionality is not limited to specific genomes, and we demonstrated its performance on both plant and human BS-seq data. MethylC-analyzer is a Python- and R-based program designed to perform comprehensive downstream analyses of methylation data, providing an intuitive analysis platform for scientists unfamiliar with DNA methylation analysis. It is available as either a standalone version for command-line uses or a graphical user interface (GUI) and is publicly accessible at https://github.com/RitataLU/MethylC-analyzer.
Motivating youth to learn STEM through a gender inclusive digital forensic science program
Authors: Casey Eoghan , Jocz Jennifer , Peterson Karen A. , Pfeif Daryl , Soden Cassy
Published: January 2023

This paper describes the design, implementation and research of the Cyber Sleuth Science Lab (CSSL), an innovative educational program and supporting virtual learning environment, that combines pedagogical theory, gender inclusive instruction strategies, scientific principles/practices, gamification methods, computational thinking, and real-world problem solving. This program provides underrepresented youth, especially girls, with digital forensic knowledge, skills and career pathways, challenging them to explore complex social issues related to technology and to become cyber sleuths using real-world digital forensic methods and tools to solve investigative scenarios. Students also learn about related careers while improving their cyber street smarts. The CSSL incorporates additional “outside of the computer” activities to strengthen students’ engagement such as structured in-classroom discussions, mock trials, and in-person interactions with practitioner role models. The CSSL was piloted in various forms to assess the suitability for in-school and out-of-school settings, and the students predominantly represented racial minorities. Research in this project relied on a mixed methods approach for data collection and analysis,
including qualitative and quantitative methods, reinforced using learning analytics generated from the students clicking through the interface and interacting with the system. Analysis of gathered data indicate that the virtual learning environment developed in this project is highly effective for teaching digital forensic knowledge, skills, and abilities that are directly applicable in the workplace. Furthermore, the strategies for gender inclusive STEM instruction implemented in CSSL are effective for engaging girls without being harmful to boys’ engagement. Learning STEM through digital forensic science taps into girls’ motivations to address real-world problems that have direct relevance to their lives, and to protect and serve their community. After participating in the educational program, girls expressed a significantly greater increase in interest, relative to boys, in learning more about careers related to digital forensics and cybersecurity.
RLS-0071, a dual-targeting anti-inflammatory peptide - biomarker findings from a first in human clinical trial
Authors: Goss Jessica , Hair Pamela , Kumar Parvathi , Iacono Giuseppina , Redden Laura , Morelli Gaetano , Krishna Neel , Thienel Ulrich , Cunnion Kenji
Published: January 2023

Background

RLS-0071 is a novel 15 amino acid peptide dual-targeting anti-inflammatory inhibitor of complement and neutrophil effectors. RLS-0071 inhibits classical complement pathway activation at C1 and blocks the enzymatic activity of myeloperoxidase that leads to the generation of hypochlorous acid and induces NETosis. This peptide is being developed for the treatment of neonatal hypoxic ischemic encephalopathy (HIE) and neutrophilic pulmonary diseases.

Methods

This was a first in human clinical trial in healthy volunteers to assess safety and pharmacokinetics of single and multiple ascending doses of RLS-0071.

Results

RLS-0071 single and multiple doses were not associated with any clinically significant changes in safety parameters, laboratory test results or ECG measurements. Adverse events were similar between active drug and placebo groups. The pharmacokinetic profile demonstrated dose proportionality and two-compartment kinetics with rapid tissue distribution. Exploratory biomarker and target engagement assays demonstrated dose dependent classical complement pathway inhibition and myeloperoxidase binding.

Discussion/Conclusion

RLS-0071 was shown to be safe and well-tolerated at all doses tested with rapid tissue distribution and target engagement for both the classical complement pathway and myeloperoxidase. The findings are supportive of further clinical development and evaluation of RLS-0071 in conditions such as HIE and acute pulmonary diseases.

Trial registration

ClinicalTrials.gov Identifier: NCT05298787 March 28, 2022. Retrospectively registered.
Echogenicity and size of substantia nigra on transcranial sonography (TCS) in patients with attention-deficit/hyperactivity disorder and healthy children aged 6–12 years: a comparative study
Authors: Sepehrmanesh Zahra , Asayeshi Alireza , kakhki Reza Daneshvar , Assarian Fatemeh , Rahimi Habibolla , Arani Saeideh Ramezani moghadam
Published: January 2023

Background

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders. Children with ADHD may experience significant functional problems, such as academic concerns at school, poor interpersonal relationships and low self-esteem. Current models of ADHD suggest that it is associated with functional impairments in dopamine and norepinephrine systems. The substantia nigra in the midbrain produces the largest amount of dopamine in the brain. The present study was conducted using TCS to compare the size and echogenicity of substantia nigra between ADHD and healthy children.

Results

This cross-sectional, analytical study was conducted on 68 (34 ADHD and 34 healthy individuals) aged 6–12 years. Based on the results obtained, the hyper-echogenicity of SN in control and ADHD groups were 33.3% and 66.7% (P < 0.001) and hypo-echogenicity of thalamic nuclei were 55.2% and 44.8% (P < 0.05), respectively. Interestingly, the TCS results of healthy children with a positive family history of ADHD were similar to results for patients with the disorder.

Conclusions

The echogenicity of Substantia nigra and thalamus nucleus among children and adolescents with ADHD is significantly higher from that in healthy children.
Key design elements of successful acute ischemic stroke treatment trials
Authors: Yperzeele L. , Shoamanesh A. , Venugopalan Y. V. , Chapman S. , Mazya M. V. , Charalambous M. , Caso V. , Hacke W. , Bath P. M. , Koltsov I.
Published: January 2023

Purpose

We review key design elements of positive randomized controlled trials (RCTs) in acute ischemic stroke (AIS) treatment and summarize their main characteristics.

Method

We searched Medline, Pubmed and Cochrane databases for positive RCTs in AIS treatment. Trials were included if (1) they had a randomized controlled design, with (at least partial) blinding for endpoints, (2) they tested against placebo (or on top of standard therapy in a superiority design) or against approved therapy; (3) the protocol was registered and/or published before trial termination and unblinding (if required at study commencement); (4) the primary endpoint was positive in the intention to treat analysis; and (5) the study findings led to approval of the investigational product and/or high ranked recommendations. A topical approach was used, therefore the findings were summarized as a narrative review.

Findings

Seventeen positive RCTs met the inclusion criteria. The majority of trials included less than 1000 patients (n = 15), had highly selective inclusion criteria (n = 16), used the modified Rankin score as a primary endpoint (n = 15) and had a frequentist design (n = 16). Trials tended to be national (n = 12), investigator-initiated and performed with public funding (n = 11).

Discussion

Smaller but selective trials are useful to identify efficacy in a particular subgroup of stroke patients. It may also be of advantage to limit the number of participating countries and centers to avoid heterogeneity in stroke management and bureaucratic burden.

Conclusion

The key characteristics of positive RCTs in AIS treatment described here may assist in the design of further trials investigating a single intervention with a potentially high effect size.
Implementation and experimental evaluation of dynamic capabilities in wireless body area networks: different setting parameters and environments
Authors: Thippun Pitchakron , Sasiwat Yoschanin , Buranapanichkit Dujdow , Booranawong Apidet , Jindapetch Nattha , Saito Hiroshi
Published: January 2023

It is well known that a wireless body area network (WBAN) is a special proposed wireless sensor network (WSN) that can assist in monitoring physiological signals for the evaluation and planning of patient treatment. One of the most challenging issues for WBANs is communication reliability, with acceptable communication efficiency and packet loss. To obtain such network characteristics, collision-free data transmission in networks of wireless sensor nodes is an interesting research problem. In this paper, the experiments of dynamic capabilities in several WBAN scenarios are focused, where the novelty and major contribution of our tests is that the effects of packet inter-arrival times, packet sizes, and the number of nodes deployed in the network, including human movements, indoor and outdoor environments, and transmitter and receiver positions, are all taken into consideration and evaluated. This is achieved by implementing the WBAN using IEEE 802.15.4 low-power sensor nodes. Experimental results illustrate the significant factors that impact the communication reliability of WBANs as measured by the packet delivery ratio (PDR). The experimental results show that the diverse environment testbed can affect network performance for WBAN data transmission. Our findings also show that the best network reliability needs to be set at more than 15 ms in packet interval time to achieve over 90% PDR for every test scenario. More details of the experimental results related to WBAN reliability obtained from all test cases are also discussed and summarized in the paper. To the best of our knowledge, our findings can be useful for users and researchers to consider the optimal point for WBAN setting and configuration to achieve the communication reliability requirements and also to deploy and develop a more reliable WBAN system.
The impact of trauma and daily hardships on the mental health of unaccompanied refugee minors detained in Libya
Authors: Derluyn Ilse , Orsini Giacomo , Verhaeghe Floor , Elhaj Rihab , Lietaert Ine , Pfeiffer Elisa
Published: January 2023

Background

The high trauma load and prevalence of mental distress in unaccompanied refugee minors (URMs) who resettle in Western (European) countries is well documented. However, the lack of studies investigating the potentially most vulnerable population, URMs who are currently on the move in transit countries such as Libya, is alarming.

Aims

To document the mental health of URMs detained in Libya and the possible associations with trauma, flight and daily hardships.

Method

In total n = 99 (94.9% male; n = 93) URMs participated in this cross-sectional study conducted in four detention centres near the Libyan capital Tripoli. Data were collected via standardised questionnaires in an interview format and analysed using structured equation modelling.

Results

Participants reported high rates of trauma, especially within Libya itself. Reports of daily hardships in detention ranged between 40 and 95% for basic needs and between 27 and 80% for social needs. Higher social needs were associated with increased anxiety symptoms (β = 0.59; P = 0.028) and increased pre-migration (β = 0.10; P = 0.061) and peri-migration trauma (β = 0.16; P = 0.017) with symptoms of depression. Similarly, higher levels of pre-migration trauma were associated with higher post-traumatic stress disorder levels (β = 0.17; P = 0.010).

Conclusions

The rates of daily hardships and traumatic events are higher compared with those recorded for URMs living in asylum centres in Europe. The emotional, social and cognitive development of detained URMs is severely threatened in both the short and long term. This paper outlines some of the most detrimental effects of migration policies on URMs transiting through Libya.
Historic Clinical Trial External Control Arm Provides Actionable GEN-1 Efficacy Estimate Before a Randomized Trial
Authors: Yin Xiang , Davi Ruthanna , Lamont Elizabeth B. , Thaker Premal H. , Bradley William H. , Leath Charles A. , Moore Kathleen M. , Anwer Khursheed , Musso Lauren , Borys Nicholas
Published: January 2023

PURPOSE

To inform continued development of the novel immune agent GEN-1, we compared ovarian cancer patients' end points from a neoadjuvant single-arm phase IB study with those of similar historic clinical trial (HCT) patients who received standard neoadjuvant chemotherapy.

METHODS

Applying OVATION-1 trial (ClinicalTrials.gov identifier: NCT02480374 ) inclusion and exclusion criteria to Medidata HCT data, we identified historical trial patients for comparison. Integrating patient-level Medidata historic trial data (N = 41) from distinct neoadjuvant ovarian phase I-III trials with patient-level OVATION-1 data (N = 18), we selected Medidata patients with similar baseline characteristics as OVATION-1 patients using propensity score methods to create an external control arm (ECA).

RESULTS

Fifteen OVATION-1 patients (15 of 18, 83%) were matched to 15 (37%, 15 of 41) Medidata historical trial control patients. Matching attenuated preexisting differences in attributes between the groups. The median progression-free survival time was not reached by the OVATION-1 group and was 15.8 months (interquartile range, 11.40 months to nonestimable) for the ECA. The hazard of progression was 0.53 (95% CI, 0.16 to 1.73), favoring GEN-1 patients. Compared with ECA patients, OVATION-1 patients had more nausea, fatigue, chills, and infusion-related reactions.

CONCLUSION

Comparing results of a single-arm early-phase trial to those of a rigorously matched HCT ECA yielded insights regarding comparative efficacy prior to a randomized controlled trial. The effect size estimate itself informed both the decision to continue development and the randomized phase II trial (ClinicalTrials.gov identifier: NCT03393884 ) sample size. The work illustrates the potential of HCT data to inform drug development.
Textual Representations of Greek Christianity during the English Reformations
Authors: Stylianou Anastasia
Published: January 2023

Early modern Anglo-Hellenic relations have received little scholarly attention; however, Greek Christianity had a significant influence on the English Reformations. This article analyzes sixteenth-century English textual contacts with, and constructions of, Greek Christianity. It highlights the importance of Greek Christian history (from the patristic era to the fall of Constantinople) to reformers across the confessional spectrum, and investigates the various uses of this history in justifying or criticizing England's break with Rome, focusing upon the government's propaganda tracts of the 1530s, Reginald Pole's De Unitate, and John Foxe's Acts and Monuments. It also examines the Venetian-Greek Nicander Nucius's depiction of the Henrician Reformation in his autobiography, exploring how this unique account was shaped by Nicander's religious beliefs. Eastern Christianity must be incorporated into historical narratives of the English Reformations in order to understand fully the confessional debates, encounters, and identities of the period.
From Rabbis and Millenarians to High Church Orthodoxy: Edward Bernard (1638–1697) Reads the 1646 Amsterdam Vocalized Mishnah
Authors: Roebuck Thomas
Published: January 2023

The vocalized edition of the Mishnah (the ancient compilation of Jewish oral teachings) published in Amsterdam in 1646 has long been an object of fascination to scholars. The story of its creation at the confluence of Jewish publishing and Christian millenarian enthusiasm is well-known. However, it was long believed that seventeenth-century Christian readers ignored the book, a view that has only recently begun to be challenged. This article joins that challenge and introduces a vital new source: a copy in the Bodleian Library that has been heavily annotated by a Christian reader, who the article demonstrates was Edward Bernard (1638 – 1697), Savilian Professor of Astronomy at Oxford University and a passionate student of languages. Discussion of the astonishingly rich annotations reveals that this copy—and therefore this edition more broadly—was a crucial linchpin in the history of Christian study of the Mishnah in the seventeenth century.