bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractBackgroundGermline 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 methodsData 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.ResultsFifty-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.ConclusionOur 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

AbstractDNA 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

AbstractThis 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

Abstract
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

Abstract
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

Abstract
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

AbstractIt 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.
Establishment of a novel axon pruning model of Drosophila motor neuron
Authors: Xu Wanyue , Kong Weiyu , Gao Ziyang , Huang Erqian , Xie Wei , Wang Su , Rui Menglong 
Published: January 2023

ABSTRACT
Developmental neuronal pruning is a process by which neurons selectively remove excessive or unnecessary neurite without causing neuronal death. Importantly, this process is widely used for the refinement of neural circuits in both vertebrates and invertebrates, and may also contribute to the pathogenesis of neuropsychiatric disorders, such as autism and schizophrenia. In the peripheral nervous system (PNS), class IV dendritic arborization (da) sensory neurons of Drosophila, selectively remove the dendrites without losing their somas and axons, while the dendrites and axons of mushroom body (MB) γ neuron in the central nervous system (CNS) are eliminated by localized fragmentation during metamorphosis. Alternatively, dendrite pruning of ddaC neurons is usually investigated via live-cell imaging, while dissection and fixation are currently used for evaluating MB γ neuron axon pruning. Thus, an excellent model system to assess axon specific pruning directly via live-cell imaging remains elusive. Here, we report that the Drosophila motor neuron offers a unique advantage for studying axon pruning. Interestingly, we uncover that long-range projecting axon bundle from soma at ventral nerve cord (VNC), undergoes degeneration rather than retraction during metamorphosis. Strikingly, the pruning process of the motor axon bundle is straightforward to investigate via live imaging and it occurs approximately at 22 h after pupal formation (APF), when axon bundles are completely cleared. Consistently, the classical axon pruning regulators in the Drosophila MB γ neuron, including TGF-β signaling, ecdysone signaling, JNK signaling, and the ubiquitin-proteasome system are also involved in governing motor axon pruning. Finally, our findings establish an unprecedented axon pruning mode that will serve to systematically screen and identify undiscovered axon pruning regulators.
This article has an associated First Person interview with the first author of the paper.