bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and evaluation of circulating small extracellular vesicle microRNAs as diagnostic biomarkers for patients with indeterminate pulmonary nodules
Authors: Zheng Di , Zhu Yuming , Zhang Jiyang , Zhang Wei , Wang Huizhen , Chen Hao , Wu Chunyan , Ni Jian , Xu Xiaoya , Nian Baoning , Chen Sheng , Wang Beibei , Li Xiaofang , Zhang Yanan , Zhang Jiatao , Zhong Wenzhao , Xiong Lei , Li Fugen , Zhang Dadong , Xu Jianfang , Jiang Gening 
Published: April 2022

Abstract
Background
The identification of indeterminate pulmonary nodules (IPNs) following a low-dose computed tomography (LDCT) is a major challenge for early diagnosis of lung cancer. The inadequate assessment of IPNs’ malignancy risk results in a large number of unnecessary surgeries or an increased risk of cancer metastases. However, limited studies on non-invasive diagnosis of IPNs have been reported.

Methods
In this study, we identified and evaluated the diagnostic value of circulating small extracellular vesicle (sEV) microRNAs (miRNAs) in patients with IPNs that had been newly detected using LDCT scanning and were scheduled for surgery. Out of 459 recruited patients, 109 eligible patients with IPNs were enrolled in the training cohort (n = 47) and the test cohort (n = 62). An external cohort (n = 99) was used for validation. MiRNAs were extracted from plasma sEVs, and assessed using Small RNA sequencing. 490 lung adenocarcinoma samples and follow-up data were used to investigate the role of miRNAs in overall survival.

Results
A circulating sEV miRNA (CirsEV-miR) model was constructed from five differentially expressed miRNAs (DEMs), showing 0.920 AUC in the training cohort (n = 47), and further identified in the test cohort (n = 62) and in an external validation cohort (n = 99). Among five DEMs of the CirsEV-miR model, miR-101-3p and miR-150-5p were significantly associated with better overall survival (p = 0.0001 and p = 0.0069). The CirsEV-miR scores were calculated, which significantly correlated with IPNs diameters (p < 0.05), and were able to discriminate between benign and malignant PNs (diameter ≤ 1 cm). The expression patterns of sEV miRNAs in the benign, adenocarcinoma in situ/minimally invasive adenocarcinoma, and invasive adenocarcinoma subgroups were found to gradually change with the increase in aggressiveness for the first time. Among all DEMs of the three subgroups, five miRNAs (miR-30c-5p, miR-30e-5p, miR-500a-3p, miR-125a-5p, and miR-99a-5p) were also significantly associated with overall survival of lung adenocarcinoma patients.

Conclusions
Our results indicate that the CirsEV-miR model could help distinguish between benign and malignant PNs, providing insights into the feasibility of circulating sEV miRNAs in diagnostic biomarker development.
Trial registration: Chinese Clinical Trials: ChiCTR1800019877. Registered 05 December 2018, https://www.chictr.org.cn/showproj.aspx?proj=31346.

Graphical Abstract
Amphipathic dendritic poly-peptides carrier to deliver antisense oligonucleotides against multi-drug resistant bacteria in vitro and in vivo
Authors: Chen Zhou , Hu Yue , Mao Xinggang , Nie Dan , Zhao Hui , Hou Zheng , Li Mingkai , Meng Jingru , Luo Xiaoxing , Xue Xiaoyan 
Published: April 2022

Abstract
Background
Outbreaks of infection due to multidrug-resistant (MDR) bacteria, especially Gram-negative bacteria, have become a global health issue in both hospitals and communities. Antisense oligonucleotides (ASOs) based therapeutics hold a great promise for treating infections caused by MDR bacteria. However, ASOs therapeutics are strangled because of its low cell penetration efficiency caused by the high molecular weight and hydrophilicity.

Results
Here, we designed a series of dendritic poly-peptides (DPP1 to DPP12) to encapsulate ASOs to form DSPE-mPEG2000 decorated ASOs/DPP nanoparticles (DP-AD1 to DP-AD12) and observed that amphipathic DP-AD2, 3, 7 or 8 with a positive charge ≥ 8 showed great efficiency to deliver ASOs into bacteria, but only the two histidine residues contained DP-AD7 and DP-AD8 significantly inhibited the bacterial growth and the targeted gene expression of tested bacteria in vitro. DP-AD7anti-acpP remarkably increased the survival rate of septic mice infected by ESBLs-E. coli, exhibiting strong antibacterial effects in vivo.

Conclusions
For the first time, we designed DPP as a potent carrier to deliver ASOs for combating MDR bacteria and demonstrated the essential features, namely, amphipathicity, 8–10 positive charges, and 2 histidine residues, that are required for efficient DPP based delivery, and provide a novel approach for the development and research of the antisense antibacterial strategy.

Graphical Abstract
Quality of life and mental health in emerging adults with cerebral palsy compared to the general population
Authors: Schmidt Silke , Markwart Henriette , Rapp Marion , Guyard Audrey , Arnaud Catherine , Fauconnier Jérôme , Thyen Ute , Hahm Stefanie , Vidart d’Egurbide Bagazgoïtia Nicolas , Muehlan Holger 
Published: April 2022

Abstract
Background
While evidence concerning Quality of Life (QoL) in youth with cerebral palsy (CP) in comparison to the general population has been accumulating, there is a lack of studies exploring differences on a wider range of positive and negative mental health outcomes in emerging adults.

Methods
This binational case control study is part of the SPARCLE cohort study on QoL and participation of youth with CP. QoL (WHOQOL-BREF), depression (PHQ-9), anxiety (GAD-7) and self-efficacy (GSE) were assessed in 198 emerging adults with CP and 593 emerging adults from the general population, matched for country of residence, age and gender. ANCOVAs with impairment and pain as covariates were run.

Results
Similar levels of QoL were found in both samples, except for the environmental domain, with better QoL for emerging adults with CP compared to the general population. There were significant descriptive differences regarding depression with worse levels in the CP sample, however, also worse levels of self-efficacy. Pain as a covariate had a significant negative impact on all measures, leading to poorer self-efficacy while worsening depression and anxiety; impairment had a significant worsening impact on physical QoL and self-efficacy only.

Conclusion
Similar expressions of mental health outcomes in emerging adults with CP and the general population indicate the high adaptive capability of emerging adults with CP.
Adaptation and validation of the HIV Knowledge Questionnaire-18 for the general population of Indonesia
Authors: Arifin Bustanul , Rokhman M. Rifqi , Zulkarnain Zulkarnain , Perwitasari Dyah Aryani , Manggau Marianti , Rauf Saidah , Noor Rasuane , Padmawati Retna Siwi , Postma Maarten J. , Massi Muhammad Nasrum , van der Schans Jurjen 
Published: April 2022

Abstract
Background
Despite a global decline in new HIV/AIDS cases in low-middle countries, cases are increasing in Indonesia. Low knowledge about the disease among the general population is one of the major factors responsible for this trend. Indonesia does not have a validated instrument to assess HIV/AIDS knowledge. The HIV Knowledge Questionnaire-18 (HIV-KQ-18) has been translated into several languages and is one of the most extensively used instruments for assessing HIV/AIDS knowledge. This paper describes the process of adapting and validating the HIV-KQ-18, an instrument to assess the level of HIV/AIDS knowledge in the general population of Indonesia.

Methods
In the adaptation phase, feedback for the initial Bahasa Indonesia version was gathered from two HIV activists, an obstetrician, two general practitioners, and 60 pilot participants. At the validation stage, we distributed the instrument link via Google Form to 6 major regions in Indonesia. Validity was measured using known-group validity and construct validity. The construct validity was assessed using an exploratory factor analysis (EFA) with a polychoric correlation matrix. Cronbach’s alpha was used to analyze the internal consistency.

Results
Based on the findings in the adaptation phase, additional descriptions (namely synonyms or examples) were added to 6 items to make them more understandable. In the validation phase, 1,249 participants were recruited. The a priori hypothesis in known-group validity was supported. We also found three items that did not meet the construct validity. Based on the acceleration factor approach to interpret the scree tree in the factor analysis, using only two factors was preferable. Cronbach's alpha values were 0.75 and 0.71 representing good internal reliability.

Conclusion
The HIV-KQ-18 Bahasa Indonesia is considered a valid and reliable instrument to assess the level of HIV/AIDS knowledge in Indonesia.
Sense of coherence moderates the relationship between social capital and oral health‑related quality of life in schoolchildren: a 10-year cohort study
Authors: Knorst Jessica Klöckner , Vettore Mario Vianna , Brondani Bruna , Emmanuelli Bruno , Tomazoni Fernanda , Ardenghi Thiago Machado 
Published: April 2022

Abstract
Background
This study aimed to evaluate the moderating effect of sense of coherence (SOC) on the relationship between social capital and oral health-related quality of life (OHRQoL) among schoolchildren.

Methods
A cohort study was conducted in the city of Santa Maria, Brazil, involving children aged 1–5 years at baseline who were reassessed after 10 years in adolescence (11–15 years-old). Social capital was assessed at baseline and follow-up through social networks and social trust. Sense of coherence scale (SOC-13) and the short form of the Child Perceptions Questionnaire 11–14 (CPQ11–14) were measured at 10-years follow-up. Demographic and socioeconomic characteristics, and dental caries were also evaluated. Moderating effect of SOC on the relationship between social capital and OHRQoL was tested using multilevel adjusted Poisson regression analysis and simple slope test.

Results
From the 639 subjects assessed at baseline, 429 were reassessed at follow-up (cohort retention rate 67.1%). Moderate and high levels of SOC demonstrated a moderating effect on the relationship between social capital and OHRQoL. Among individuals who presented low social capital at baseline and follow-up, those who had high SOC reported, respectively, an impact 63% and 70% lower on OHRQoL when compared to those with low SOC. The greatest margin effect was observed in individuals with low social capital and low SOC at follow-up (24.25; p < 0.05).

Conclusion
Our findings suggest that SOC moderates the negative impact of low social capital on poor OHRQoL in schoolchildren.
Co-production practice and future research priorities in United Kingdom-funded applied health research: a scoping review
Authors: Smith Helen , Budworth Luke , Grindey Chloe , Hague Isabel , Hamer Natalie , Kislov Roman , van der Graaf Peter , Langley Joe 
Published: April 2022

Abstract
Background
Interest in and use of co-production in healthcare services and research is growing. Previous reviews have summarized co-production approaches in use, collated outcomes and effects of co-production, and focused on replicability and reporting, but none have critically reflected on how co-production in applied health research might be evolving and the implications of this for future research. We conducted this scoping review to systematically map recent literature on co-production in applied health research in the United Kingdom to inform co-production practice and guide future methodological research.

Methods
This scoping review was performed using established methods. We created an evidence map to show the extent and nature of the literature on co-production and applied health research, based on which we described the characteristics of the articles and scope of the literature and summarized conceptualizations of co-production and how it was implemented. We extracted implications for co-production practice or future research and conducted a content analysis of this information to identify lessons for the practice of co-production and themes for future methodological research.

Results
Nineteen articles reporting co-produced complex interventions and 64 reporting co-production in applied health research met the inclusion criteria. Lessons for the practice of co-production and requirements for co-production to become more embedded in organizational structures included (1) the capacity to implement co-produced interventions, (2) the skill set needed for co-production, (3) multiple levels of engagement and negotiation, and (4) funding and institutional arrangements for meaningful co-production. Themes for future research on co-production included (1) who to involve in co-production and how, (2) evaluating outcomes of co-production, (3) the language and practice of co-production, (4) documenting costs and challenges, and (5) vital components or best practice for co-production.

Conclusion
Researchers are operationalizing co-production in various ways, often without the necessary financial and organizational support required and the right conditions for success. We argue for accepting the diversity in approaches to co-production, call on researchers to be clearer in their reporting of these approaches, and make suggestions for what researchers should record. To support co-production of research, changes to entrenched academic and scientific practices are needed.
Protocol registration details: The protocol for the scoping review was registered with protocols.io on 19 October 2021: https://dx.doi.org/10.17504/protocols.io.by7epzje.
An assessment of adherence to the WHO-delineated good manufacturing practice by the pharmaceutical companies in Kabul, Afghanistan
Authors: Roien Rohullah , Shrestha Rajeev , Yadav Kashikant , Ozaki Akihiko , Ahmadi M. Bashir , Kaneda Yudai , Kotera Yasuhiro , Sapkota Binaya , Shrestha Sunil 
Published: April 2022

Abstract
Background
Afghanistan, a low-income landlocked country, is continuously suffering from domestic war and conflicts; the country struggles to provide quality healthcare services, including affordable medicinal products in the required quantity. Moreover, the quality standards of domestic pharmaceutical companies have not been established yet. One of the internationally recognized guidelines for monitoring manufacturing processes in pharmaceutical companies is Good Manufacturing Practice (GMP), recommended by World Health Organization (WHO). Therefore, this study aimed to assess whether a pharmaceutical company in Kabul, Afghanistan adheres to the GMP standards established by WHO.

Method
A descriptive cross-sectional study was conducted to assess the WHO-delineated GMP compliance of 25 pharmaceutical companies in Kabul, Afghanistan. The inspection checklist was developed by Afghanistan's National Medicine and Healthcare Products Regulatory Authority (NMHRA) using the WHO-delineated GMP guidelines. In addition, direct observation, interviews with respective delegates, and documentation reviews were conducted to collect research data.

Result
Only 38.33% (1.14 ± 1.08) of GMP contents were complied. Personnel 66.67% (2 ± 1.15) and materials 58.67% (1.76 ± 1.11) were the most commonly complied components, whereas the product recall 12.98% (0.39 ± 0.85), quality assurance 16.44% (0.49 ± 0.81) and quality control laboratory 28.35% (0.85 ± 1.12) were the least complied ones.

Conclusion
None of the GMP components was fully adhered to by the pharmaceutical companies in Kabul, Afghanistan. Quality control and assurance should be implemented immediately, including validation and qualification practices.
Cross-sectional and longitudinal associations of active travel, organised sport and physical education with accelerometer-assessed moderate-to-vigorous physical activity in young people: the International Children’s Accelerometry Database
Authors: Ikeda Erika , Guagliano Justin M. , Atkin Andrew J. , Sherar Lauren B. , Ekelund Ulf , Hansen Bjørge , Northstone Kate , van Sluijs Esther ,   On behalf of the International Children’s Accelerometry Database (ICAD) Collaborators, Salmon Jo , Riddoch Chris , Judge Ken , Cooper Ashley , Griew Pippa , Andersen L. B. , Anderssen S. , Cardon G. , Davey R. , Hallal P. , Jago R. , Janz K. F. , Kriemler S. , Møller N. , Northstone K. , Pate R. , Puder J. J. , Reilly J. , Salmon J. , Sardinha L. B. , van Sluijs E. M. F. 
Published: April 2022

Abstract
Background
Physical activity (PA) declines during childhood. Important sources of PA are active travel, organised sport and physical education (PE), but it is unclear how these domain-specific PA sources contribute to (changes in) daily moderate-to-vigorous PA (MVPA) in young people. This study aimed to examine (1) the cross-sectional association between domain-specific physical activity (i.e., active travel, organised sport and PE) and daily minutes in accelerometer-assessed MVPA; and (2) the longitudinal association between domain-specific physical activity at baseline and change in daily minutes in MVPA.

Methods
Participants (baseline age 11.3 ± .1.2 years) were drawn from three studies in the International Children’s Accelerometry Database. The contribution of self-reported standardised active travel, organised sport and PE to accelerometer-measured daily minutes in MVPA was examined using linear regression. In cross-sectional analyses, MVPA was regressed on each PA domain in separate models, adjusted for study, age, sex, maternal education, season, and monitor wear time. In longitudinal analyses, change in MVPA was regressed on each of the baseline PA domains, additionally adjusting for changes in season and wear time, follow-up duration, and baseline MVPA. R-squared was used to compare variance explained by each PA domain.

Results
In the cross-sectional analyses (n = 3871), organised sport (standardised β = 3.81, 95% confidence interval [95%CI] = 3.06, 4.56) and active travel (β = 3.46, 95%CI = 2.73, 4.19) contributed more to daily MVPA than PE (β = 0.82, 95%CI = -0.02, 1.66). Compared to the base model which included only covariates (R2 = 21.5%), organised sport (absolute change: + 1.9%) and active travel (+ 1.7%) models explained more of the variance than the PE model (± < 0.1%). Associations followed a similar pattern in the longitudinal analyses (n = 2302), but none of the PA domains predicted change in MVPA (organised sport: standardised β = 0.85, 95%CI = -0.03, 1.72; active travel: β = 0.68, 95%CI = -0.14, 1.50; PE: β = 0.02, 95%CI = -0.87, 0.91).

Conclusions
A multi-sectoral approach covering a wide range of PA domains should be promoted to minimise the age-related decline in MVPA during childhood.
Optimizing NK-92 serial killers: gamma irradiation, CD95/Fas-ligation, and NK or LAK attack limit cytotoxic efficacy
Authors: Navarrete-Galvan Lydia , Guglielmo Michael , Cruz Amaya Judith , Smith-Gagen Julie , Lombardi Vincent C. , Merica Rebecca , Hudig Dorothy 
Published: April 2022

AbstractBackgroundThe NK cell line NK-92 and its genetically modified variants are receiving attention as immunotherapies to treat a range of malignancies. However, since NK-92 cells are themselves tumors, they require irradiation prior to transfer and are potentially susceptible to attack by patients’ immune systems. Here, we investigated NK-92 cell-mediated serial killing for the effects of gamma-irradiation and ligation of the death receptor Fas (CD95), and NK-92 cell susceptibility to attack by activated primary blood NK cells.MethodsTo evaluate serial killing, we used51Cr-release assays with low NK-92 effector cell to target Raji, Daudi or K562 tumor cell (E:T) ratios to determine killing frequencies at 2-, 4-, 6-, and 8-h.ResultsNK-92 cells were able to kill up to 14 Raji cells per NK-92 cell in 8 h. NK-92 cells retained high cytotoxic activity immediately after irradiation with 10 Gy but the cells surviving irradiation lost > 50% activity 1 day after irradiation. Despite high expression of CD95, NK-92 cells maintained their viability following overnight Fas/CD95-ligation but lost some cytotoxic activity. However, 1 day after irradiation, NK-92 cells were more susceptible to Fas ligation, resulting in decreased cytotoxic activity of the cells surviving irradiation. Irradiated NK-92 cells were also susceptible to killing by both unstimulated and IL-2 activated primary NK cells (LAK). In contrast, non-irradiated NK-92 cells were more resistant to attack by NK and LAK cells.ConclusionsIrradiation is deleterious to both the survival and cytotoxicity mediated by NK-92 cells and renders the NK-92 cells susceptible to Fas-initiated death and death initiated by primary blood NK cells. Therefore, replacement of irradiation as an antiproliferative pretreatment and genetic deletion of Fas and/or NK activation ligands from adoptively transferred cell lines are indicated as new approaches to increase therapeutic efficacy.
Reproductive health status of adolescent mothers in an Iranian setting: a cross-sectional study
Authors: Zare Maryam , Mardi Afrouz , Gaffari-moggadam Mozhgan , Nezhad-dadgar Nazila , Abazari Malek , Shadman Atefeh , Ziapour Arash 
Published: April 2022

AbstractBackgroundIn low and middle-income countries (LMICs), where millions of women give birth before the age of 18, the reproductive health status of married adolescent mothers, including family planning, sexual, psychosocial, and maternal health, remains a significant and recurring phenomenon. As a result, the purpose of this study was to assess the reproductive health status of married adolescent mothers who sought treatment at Ardabil health care centers in 2019.MethodsA cross-sectional study was carried out in five health centers in Ardabil, Iran. This research included 312 married adolescent mothers who were under 19 years old. Health workers who asked questions of each participant completed a demographic questionnaire and the Reproductive Health Assessment Scale for Married Adolescent Women, and all data were self-reported. Univariate and multivariate linear regressions were used to determine risk factors associated with reproductive health scores. The data was examined using statistical software (SPSS version 20).ResultsThe mean age (years) of the respondents was 16.41 ± 0.85, the mean age of their husbands was 24.18 ± 2.29, and the mean age of their marriage was 15.06 ± 1.15. In this study, adolescent mothers had an average reproductive health score of 63.78 ± 11.06. There was a significant association between reproductive health status and age, education, husband’s age and education, and contraceptive methods among married adolescent mothers (p < 0.05).ConclusionThe research findings indicated that adolescent mothers had an average level of reproductive health. Several socio-demographic characteristics, including age, education, gravida, and contraception, were linked to reproductive health scores. Programmers and policymakers should prioritize improving the reproductive health of adolescent mothers through education and increasing women’s and spouses’ knowledge and awareness.