bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the Utility of EZC Pak, a 5-Day Combination Echinacea-Zinc-Vitamin C Dose Pack with or without Vitamin D, in the Management of Outpatient Upper Respiratory Infections
Authors: Radhakrishnan Aditya , Spencer Stephanie , Yanamala Naveena , Malepati Sarath 
Published: October 2022

AbstractBackgroundGrowing antibiotic resistance is among the most serious threats to healthcare systems and public health globally with antibiotic misuse considered a leading driver of this problem. One of the largest areas of antibiotic misuse is in outpatient upper respiratory infections (URIs), the most common infection in humans. The purpose of this research is to evaluate the efficacy of EZC Pak, a combination Echinacea-Zinc-Vitamin C dose pack with or without Vitamin D, on the duration of illness and symptom severity of non-specific URIs as an alternative to antibiotics when none are deemed clinically necessary. A secondary analysis was carried out on patient satisfaction with using EZC Pak.MethodsA total of 360 patients across the United States were enrolled and randomized in a double-blind manner across two intervention groups, EZC Pak, EZC Pak+Vitamin D, and one placebo group. The study was conducted virtually utilizing a smartphone-based app to screen, enroll and capture study data of the participants. Once a study participant reported the first symptoms of a URI, they were advised to take the intervention as directed and complete the daily symptom survey score until their symptoms resolved.ResultsThe average EZC Pak participant recovered 1.39 days faster than placebo (p= 0.017) than the average placebo participant. The average EZC Pak participant reported a 17.43% lower symptom severity score versus placebo (p= 0.029). EZC Pak users reported 2.9 times higher patient satisfaction versus users of the placebo (p= 0.012). The addition of Vitamin D during this acute phase of illness neither benefited nor harmed illness duration or symptom severity.ConclusionsThe findings support the potential use of EZC Pak as a viable alternative to patient request for antibiotics when none are deemed clinically necessary at the time of initial clinical presentation. The decision to replete vitamin D in the acute phase of URI is an individualized decision left to the patient and their clinician. EZC Pak may play a critical role in improving outpatient URI management and antibiotic stewardship. (ClinicalTrials.govnumber,NCT04943575.)
A panel of four miRNAs (miR-190b, miR-584-5p, miR-452-5p, and miR-1306-5p) is capable of classifying luminal and non-luminal breast cancers
Authors: Farahmand Faranak , Rahmani Saied , Bayat Hadi , Salimi Adel , Ghanbari Sogol , Shafaroudi Afsaneh Malekzadeh , Sharifi-Zarchi Ali , Vasei Mohammad , Mowla Seyed-Javad 
Published: October 2022

AbstractBACKGROUNDIdentifying the molecular subtypes of breast cancer (BC) plays a crucial role in enhancing the efficacy of therapy. MiRNAs (miRs) with differential expressions in different subtypes of breast tumors can be considered as non-invasive biomarkers for diagnosing BC subtypes.OBJECTIVEWe aimed to investigate the efficacy of miR-190b, miR-584-5p, miR-452-5p, and miR-1306-5p as novel potent diagnostic biomarkers in discriminating patients with luminal (ER+) and non-luminal (ER–) BCs.METHODSA group of miRs significantly associated with estrogen cell receptors (ER) in breast tumors were identified using feature selection methods analysis on miR-Seq datasets retrieved from TCGA and GSE68085. Four abovementioned miRs were selected as novel potential biomarkers, and their relative expression levels were assessed within adjacent non-tumor, ER+ and ER– tumor tissues by quantitative RT-PCR. Their impact on diagnosis was also evaluated by ROC curve analysis.RESULTSIn ER+ BCs compared to ER– BCs, the expression of miR-190b was remarkably increased, while the expression of miR-584-5p, miR-452-5p, and miR-1306-5p were significantly decreased. This group could discriminate ER+ and ER– BCs at an AUC of 0.973.CONCLUSIONSAccording to our findings, these four miRs are promising biomarkers in discriminating BC subtypes. The candidate miRs in parallel with histologic diagnosis methods can be applied for identifying patients who are most likely responding to specific therapies based on ER status.
Improving case detection through TB contact risk stratification by Xpert MTB/RIF Ultra and spatial parameters. Evaluation of an innovative ACF strategy in Mozambique
Authors: Saavedra Belén , Nguenha Dinis , de la Torre-Pérez Laura , Mambuque Edson , Tembe Gustavo , Oliveras Laura , Rudd Matthew , Philimone Paulo , Jose Benedita , Garcia Juan Ignacio , Gomes Neide , Munguane Shilzia , Chiconela Helio , Nhanommbe Milton , Izco Santiago , Acacio Sozinho , García-Basteiro Alberto L. 
Published: October 2022

AbstractPrompt diagnosis is critical for tuberculosis (TB) control, as it enables early treatment which in turn, reduces transmission and improves treatment outcomes. We aimed to determine the impact of the scale-up of Xpert Ultra as frontline test for TB diagnosis, and an innovative active-case finding (ACF) strategy (based on Xpert Ultra semi quantitative results and spatial parameters) on new TB cases diagnosed in a semi-rural district of Southern Mozambique. From January-December 2018 we recruited all incident TB-cases (index cases, ICs) and their household contacts (HCs). Community contacts (CCs) recruitment depended on the semi-quantitative results of Xpert Ultra of the IC and the population density of the area where the IC lived in. TB-contacts, either symptomatic or people living with HIV (regardless of symptoms), were asked for providing a spot sputum for lab-testing. Trends on TB case notification in the intervention area were compared to the previous years and to those of two districts in the south of the Maputo province (control area) using an interrupted time series analysis with and without control (CITS/ITS). A total of 1010 TB ICs (37.2% laboratory-confirmed) were recruited; 3165 HC and 4730 CC were screened for TB. Eighty-nine additional TB cases were identified through the ACF intervention (52.8% laboratory-confirmed). The ACF intervention increased by 8.2% all forms of TB cases detected in 2018. CITS model showed an increase of laboratory confirmed TB cases in the intervention district, compared to the control area. Xpert Ultratracepositive results accounted for a high proportion of laboratory confirmations in the ACF cohort (51.1% vs 13.7% of those passively diagnosed). Number needed to screen (NNS) to find a TB case differed widely among HCs (NNS:55) and CCs (153). The intervention resulted in an overall increase in TB diagnoses and higher proportion of laboratory confirmation.
Child and family experiences of a whole-system approach to physical activity: a citizen science evaluation protocol
Authors: Frazer Marie , Seims Amanda , Tatterton Michael J , Lockyer Bridget , Bingham Daniel D , Barber Sally E , Daly-Smith Andy , Hall Jennifer 
Published: October 2022

AbstractIntroductionWhole systems approaches are being adopted to tackle physical inactivity. The mechanisms contributing to changes resulting from whole system approaches are not fully understood. The voices of children and families that these approaches are designed for need to be heard to understand what is working, for whom, where, and in what context. This paper describes the protocol for the children and families’ citizen science evaluation of the JU:MP programme, a whole systems approach to increasing physical activity in children and young people aged 5-14 years in Bradford, UK.Methods and analysisThe evaluation aims to understand the lived experiences of children and families’ relationship with physical activity and participation in the JU:MP programme. The study takes a collaborative and contributory citizen science approach, including focus groups, parent-child dyad interviews and participatory research. Feedback and data will guide changes within this study and the JU:MP programme. We also aim to examine participant experience of citizen science and the suitability of a citizen science approach to evaluate a whole systems approach. Data will be analysed using Framework approach alongside iterative analysis with and by citizen scientists in the collaborative citizen science study.Ethics and disseminationEthical approval has been granted by The University of Bradford: Study One (E891-focus groups as part of the control trial, E982-parent-child dyad interviews), Study Two (E992). Results will be published in peer-reviewed journals and summaries will be provided to the participants, through schools or directly. The citizen scientists input to create further dissemination opportunities.Article SummaryStrengths and Limitations of this studyThis protocol is the first, to our knowledge, to describe a citizen science-based evaluation of a whole systems approach to physical activity with children and families.The novel and innovative study design allows children and families to be at the centre of our understanding of what encourages and discourages them to be active.By conducting citizen science as part of a reactive process evaluation, improvements to the research and the implementation can be made in real time, centred around those who matter mostThe study emphasises the importance of the research participant experience within citizen science and sets out how to evaluate and improve experience.Limitations include a small sample size. Whilst this is intentional as it will allow us to capture in depth, meaningful data over time, it will likely make it more difficult to capture a diverse range of experiences. There is an option for the children participating in the collaborative citizen science study to conduct research amongst their wider peers, this is dependent on whether they want to do this, to allow them freedom and ownership over the research
Immuno-epigenetic signature derived in saliva associates with the encephalopathy of prematurity and perinatal inflammatory disorders
Authors: Conole Eleanor L.S. , Vaher Kadi , Cabez Manuel Blesa , Sullivan Gemma , Stevenson Anna J. , Hall Jill , Murphy Lee , Thrippleton Michael J. , Quigley Alan J. , Bastin Mark E. , Miron Veronique E. , Whalley Heather C. , Marioni Riccardo E. , Boardman James P. , Cox Simon R. 
Published: October 2022

AbstractBackgroundPreterm birth is closely associated with a phenotype that includes brain dysmaturation and neurocognitive impairment, commonly termed Encephalopathy of Prematurity (EoP), of which systemic inflammation is considered a key driver. DNA methylation (DNAm) signatures of inflammation from peripheral blood associate with poor brain imaging outcomes in adult cohorts. However, the robustness of DNAm inflammatory scores in infancy, their relation to comorbidities of preterm birth characterised by inflammation, neonatal neuroimaging metrics of EoP, and saliva cross-tissue applicability are unknown.MethodsUsing salivary DNAm from 258 neonates (n = 155 preterm, gestational age at birth 23.28 – 34.84 weeks, n = 103 term, gestational age at birth 37.00 – 42.14 weeks), we investigated the impact of a DNAm surrogate for C-reactive protein (DNAm CRP) on brain structure and other clinically defined inflammatory exposures. We assessed i) if DNAm CRP estimates varied between preterm infants at term equivalent age and term infants, ii) how DNAm CRP related to different types of inflammatory exposure (maternal, fetal and postnatal) and iii) whether elevated DNAm CRP associated with poorer measures of neonatal brain volume and white matter connectivity.ResultsHigher DNAm CRP was linked to preterm status (−0.0107 ± 0.0008, compared with - 0.0118 ± 0.0006 among term infants; p < 0.001), as well as perinatal inflammatory diseases, including histologic chorioamnionitis, sepsis, bronchopulmonary dysplasia, and necrotising enterocolitis (OR range |2.00 | to |4.71|, p < 0.01). Preterm infants with higher DNAm CRP scores had lower brain volume in deep grey matter, white matter, and hippocampi and amygdalae (β range |0.185| to |0.218|). No such associations were observed for term infants. Association magnitudes were largest for measures of white matter microstructure among preterms, where elevated epigenetic inflammation associated with poorer global measures of white matter integrity (β range |0.206| to |0.371|), independent of other confounding exposures.ConclusionsEpigenetic biomarkers of inflammation provide an index of innate immunity in relation to neonatal health. Such DNAm measures complement biological and clinical metrics when investigating the determinants of neurodevelopmental differences.
Reducing delays in seeking abortion among women who visit health facilities for safe abortion service in Mekelle City, Ethiopia: Pre-post interventional study
Authors: Legesse Awol Yemane , Welday Mengistu , Hagazi Mengistu , Alemayehu Mussie , Tsadik Mache , Hailemicheal Ambachew , Meressa Beyene , Gebre Daniel , Teka Hale 
Published: October 2022

AbstractObjectivesThis study assessed the effect of health education on reducing the delay in seeking abortion in Mekelle health facilities, Tigray region, Ethiopia.DesignA pre-post interventional study design with sample size of 322 women.SettingThe study was conducted in 12 health facilities at Mekelle, Tigray, Ethiopia between February 1stthrough September 30th, 2020ParticipantsAll women who have attended safe abortion services in Mekelle health facilities during the time of the data collection period were the study population.InterventionWomen education on the Ethiopian abortion law, availability of abortion services, and optimal time of pregnancy termination using 1000 leaflets, 20 street posters for 3 months.ResultsCompared to the pre-intervention group, a much change in reducing the gestational age in weeks was observed in the post intervention period to terminate the pregnancy with 9.8 decrease per 100 respondents (95% CI 9.25 to 10.36) and a Cohen’s d value of 5.23 was found. Besides, there was statistically significant difference between the pre and post-intervention on the respondent knowledge on the possibility of termination pregnancy based on wish according to Ethiopian abortion law at a p-value of < 0.024.ConclusionsWomen’s health education on the availability of safe service and optimal gestational age for termination has led to a significant reduction of the delay in weeks with large effect size. Moreover, it brings a statistically significant difference on respondent knowledge of Ethiopian abortion law. We recommend further randomized contrail study involving three face delays of safe abortion service.
Malaria parasite density and detailed qualitative microscopy enhances large-scale profiling of infection endemicity in Nigeria
Authors: Oyibo Wellington , Latham Victoria , Oladipo Oladosu , Ntadom Godwin , Uhomoibhi Perpetua , Ogbulafor Nnnena , Okoronkwo Chukwu , Okoh Festus , Mahmoud Aminu , Shekarau Emmanuel , Oresanya Olusola , Cherima Yakubu Joel , Jalingo Innua , Abba Bintu , Audu Mohammed , Conway David J. 
Published: October 2022

AbstractWith global progress towards malaria reduction stalling, further analysis of the epidemiology is required, particularly in countries with the highest burden. National surveys have mostly analysed infection prevalence, while large-scale data on parasite density and different developmental forms are rarely available. In Nigeria, the country with the largest burden globally, blood slide microscopy of children up to five years of age was conducted in the 2018 National Demographic and Health Survey, and infection prevalence previously reported. In the current study, malaria parasite density measurements are reported and analysed for 7783 of the children sampled across the 36 states within the six geopolitical zones of the country, with asexual and sexual stages considered separately and comparisons of infections with different malaria parasite species being performed. Across all states of Nigeria, there was a positive correlation between mean asexual parasite density in peripheral blood of infected individuals and prevalence of infection in the community (Spearman’s rho = 0.39, P = 0.02). Asexual parasite densities were highest in the northern geopolitical zones (geometric means > 2000 μL-1), extending the evidence of exceptionally high infection burden in many areas. Sexual parasite prevalence in each state was highly correlated with asexual parasite prevalence (Spearman’s rho = 0.70, P < 0.001), although sexual parasite densities were low (geometric means < 100 μL-1in all zones). Infants had lower parasite densities than children above one year of age, but there were no differences between male and female children. Most infections were ofP. falciparum, which had higher asexual densities but lower sexual parasite densities thanP. malariaeorP. ovalemono-infections. However, mixed species infections had the highest asexual parasite densities. It is recommended that future large surveys in high burden countries measure parasite densities as well as developmental stages and species, to improve the quality of malaria epidemiology and tracking of future changes.
“Running on goodwill and fairydust” - midwives’ experiences of facilitating and delivering local breastfeeding support via Facebook groups: a qualitative descriptive study
Authors: Morse H. , Brown A. 
Published: October 2022

BackgroundThe use of groups for providing and accessing breastfeeding support on Facebook (BSF) is now widespread, including groups aimed specifically at mothers in specific areas. Some of these groups are created and/or facilitated by midwives, but little is known about their motivations or experiences.ObjectiveTo examine how midwives involved in providing breastfeeding support via a local BSF group perceive the value of this provision and what are their experiences of creating these services and of engaging with mothers online.MethodsSemi-structured interviews were conducted with midwives between July-September 2021, and thematically analysed.ResultsThree themes were identified in relation to the research question: (1) Imperatives and Value, (2) Goodwill & lack of resources, (3) Community of Practice. Theme 1 described that groups were seen as a necessary part of developing services to meet the needs and expectations of the current generation of mothers, and to improve dire breastfeeding rates. Theme 2 identified that BSF groups are reliant on both midwives and peer supporters working voluntarily, issues of sustainability and frustration at the lack of value placed on their time, skill and investment. Theme 3 highlighted the function of BSF groups as communities of practice, providing opportunities for social learning for all members and personal and professional benefits for midwives.ConclusionsFindings have identified that midwives become involved in delivering online support motivated by a belief in the value of this provision, but feel unsupported by wider services in doing so. Midwives have concerns about the sustainability of this provision regardless of its value whilst it remains reliant on volunteers, and call for further support. Significant benefits for midwives derived from involvement were highlighted which should inform further research, guidance and investment.
Kinship and genetic variation in aquarium-spawnedAcropora hyacinthuscorals
Authors: López-Nandam Elora H. , Payne Cheyenne Y. , Delbeek J. Charles , Dunker Freeland , Krol Lana , Larkin Lisa , Lev Kylie , Ross Richard , Schaeffer Ryan , Yong Steven , Albright Rebecca 
Published: October 2022

ABSTRACTRecent scientific advances inex situsystem design and operation make it possible to complete gametogenic cycles of broadcast spawning corals. Breeding corals in aquaria are critical advances for population management, particularly genetic rescue and assisted gene flow efforts. Genetic rescue projects for corals are already underway to bring threatened species intoex situculture and propagation, thereby preserving standing genetic variation. However, while breeding corals is increasingly feasible, the consequences of the aquarium environment on the genetic and phenotypic composition of coral populations is not yet known. The aquarium environment may in itself be a selective pressure on corals, but it also presents relaxed selective pressure in other respects. In 2019 and 2020, gravidAcropora hyacinthuscoral colonies were collected from Palauan reefs and shipped to the California Academy of Sciences (CAS) in San Francisco. In both years, gametes were batch-fertilized to produce larvae that were then settled and reared to recruits. As of April 2021, when they were sampled for sequencing, 23 corals produced at CAS in 2019 and 16 corals produced at CAS in 2020 had survived for two years and one year, respectively. We sequenced the full genomes of the 39 offspring corals and their 15 potential parents to a median 26x depth of coverage. We find clear differential parentage, with some parents producing the vast majority of offspring, while the majority of parents produced no surviving offspring. After scanning 12.9 million single nucleotide polymorphisms (SNPs), we found 887 SNPs that may be under selection in the aquarium environment, and we identified the genes and pathways these SNPs may affect. We present recommendations for preserving standing genetic variation in aquarium-bred corals based on the results of this pilot project.
Changes in calpain-2 expression during glioblastoma progression predisposes tumor cells to temozolomide resistance by minimizing DNA damage and p53-dependent apoptosis
Authors: Stillger Maren Nicole , Chen Chia-Yi , Lai Zon Weng , Li Mujia , Schaefer Agnes , Pagenstecher Axel , Nimsky Christopher , Bartsch Joerg Walter , Schilling Oliver 
Published: October 2022

AbstractBackgroundGlioblastoma multiforme (GBM) is characterized by an unfavorable prognosis for patients affected. During standard-of-care chemotherapy using temozolomide (TMZ), tumors acquire resistance thereby causing tumor recurrence. Thus, deciphering essential molecular pathways causing TMZ resistance are of high therapeutic relevance.MethodsMass spectrometry based proteomics were used to study the GBM proteome. Immunohistochemistry staining of human GBM tissue for either calpain-1 or −2 was performed to locate expression of proteases.In vitrocell based assays were used to measure cell viability and survival of primary patient-derived GBM cells and established GBM cell lines after TMZ +/− calpain inhibitor administration. shRNA expression knockdowns of either calpain-1 or calpain-2 were generated to study TMZ sensitivity of the specific subunits. The Comet assay and ɣH2AX signal measurements were performed in order to assess the DNA damage amount and recognition. Finally, quantitative real-time PCR of target proteins was applied to differentiate between transcriptional and post-translational regulation.ResultsCalcium-dependent calpain proteases, in particular calpain-2, are more abundant in glioblastoma compared to normal brain and increased in patient-matched initial and recurrent glioblastomas. On the cellular level, pharmacological calpain inhibition increased the sensitivities of primary glioblastoma cells towards TMZ. A genetic knockdown of calpain-2 in U251 cells led to increased caspase-3 cleavage and sensitivity to neocarzinostatin, which rapidly induces DNA strand breakage. We hypothesize that calpain-2 causes desensitization of tumor cells against TMZ by preventing strong DNA damage and subsequent apoptosis via post-translational TP53 inhibition. Indeed, proteomic comparison of U251 control vs. U251 calpain-2 knockdown cells highlights perturbed levels of numerous proteins involved in DNA damage response and downstream pathways affecting TP53 and NF-κB signaling. TP53 showed increased protein abundance, but no transcriptional regulation.ConclusionTMZ-induced cell death in the presence of calpain-2 expression appears to favor DNA repair and promote cell survival. We conclude from our experiments that calpain-2 expression represents a proteomic mode that is associated with higher resistance via “priming” GBM cells to TMZ chemotherapy. Thus, calpain-2 could serve as a prognostic factor for GBM outcome.