bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tailoring an online breastfeeding course for Southeast Asian paediatric trainees- A qualitative study of user experience from Malaysia and Thailand
Authors: Lee Yew Kong , Wattanapisit Apichai , Ng Chirk Jenn , Boey Christopher Chiong Meng , Ahmad Kamar Azanna , Choo Yao Mun , Hong Joyce Soo Synn , Cheah Fook Choe , Tang Swee Fong , Poh Bee Koon , Chongviriyaphan Nalinee , Siwarom Sirinapa , Visuthranukul Chonnikant , Koletzko Berthold 
Published: March 2022

Abstract
Background
This study explored the user experiences of paediatric postgraduate trainees in Malaysia and Thailand in using a 2 h and 15 min online module for breastfeeding developed for Southeast Asia, which was adapted from existing European online modules for European and German Continuing Medical Education (CME) credits.

Methods
A qualitative study using focus group discussions (FGDs) was conducted with paediatric postgraduate trainees who used an online English-language breastfeeding module in two Thai universities (May 2020, done online) and two Malaysian universities (Sept- Nov 2019, in-person). FGDs explored module usability and utility. Sessions were transcribed verbatim and analysed thematically. The process of coding was done collaboratively by Thai and Malaysian researchers.

Results
Twenty Six resident trainees participated (Thai, n = 13; Malaysian, n = 13). Ages ranged from 29–34 years old, with 21 females. Nineteen participants had never used online learning modules prior to this. Participants took between 1 to 5 sessions to complete the breastfeeding module. Four themes emerged from their experience. 1) The online learning module was more engaging and detailed than previous lectures, courses and/or books, but lacked hands-on training. 2) Using an online platform facilitated learning as eased navigation and resource searching, however, problems were encountered navigating the module on some devices. 3) Learners preferred less words and more graphics, as this helped them capture key messages. 4) Regionally tailored content elicited a mixed reaction from participants.

Conclusions
Users found that the adapted module compared favourably with previous learning experiences. However, online learning modules lack hands-on training, and implementation should ideally incorporate a mix of both. Consideration of device diversity and preferences for how content was adapted for local settings are needed for tailoring.
Collection and use of human materials during TB clinical research; a review of practices
Authors: Ochieng Joseph , Kwagala Betty , Sewankambo Nelson 
Published: March 2022

Abstract
Background
Human biological materials are usually stored for possible future use in research because they preserve valuable biological information, save time and resources, which would have been spent on collection of fresh samples. However, use of these materials may pose ethical challenges such as unauthorized disclosure of genetic information, which can result in dire consequences for individuals or communities including discrimination, stigma, and psychological harm; has biosecurity implications; and loss of control or ownership of samples or data. To understand these problems better, we evaluated the extent to which tuberculosis (TB) clinical research protocols that were used to collect and store biological materials for future use conform to the requirements stated in the Uganda national guidelines for research involving humans as participants.

Methods
This was a retrospective review of TB clinical research projects approved by the Uganda National Council for Science and Technology (UNCST) from 2011 to 2015, to examine whether they fulfilled the requirements for ethical collection and use of human materials. Data were abstracted through review of the project protocols using a template developed based on the informed consent and the Materials Transfer Agreement (MTA) requirements in the national guidelines.

Results
Out of 55 research protocols reviewed, most of the protocols 83.6% had been used to collect the stored samples (sputum, blood and sometimes urine), 28% had a section on specimen collection and 24% mentioned ownership of the biological materials. With respect to review of the consent forms used in the studies that stored materials for future use, only 9% of the protocols had a separate consent form for storage of materials, 4.5% of the consent forms explained the risks, 11.4% explained the purpose of the study while 6.8% mentioned the place of storage for the collected materials.

Conclusion
Many of the studies reviewed did not meet the requirements for collection and storage of biological materials contained in the national guidelines, which indicates a need to additional training on this topic.
The repertoire of testicular extracellular vesicle cargoes and their involvement in inter-compartmental communication associated with spermatogenesis
Authors: Choy Kathleen Hoi Kei , Chan Sze Yan , Lam William , Jin Jing , Zheng Tingting , Law Tin Yu Samuel , Yu Sidney Siubun , Wang Weiping , Li Linxian , Xie Gangcai , Yim Howard Chi Ho , Chen Hao , Fok Ellis Kin Lam 
Published: March 2022

Abstract
Background
Spermatogenesis is regulated by a complex network of intercellular communication processes. Extracellular vesicles (EVs) are one of the important mediators in intercellular communication. Previous reports have demonstrated the involvement of EVs from the epididymis and prostate in sperm maturation and function. However, the presence of EVs in the testis and their potential involvement in spermatogenesis has not been explored. Here, we have established a testis dissociation protocol that allows the isolation and characterization of testicular EVs.

Results
We show that testicular EVs are specifically and efficiently taken up by somatic cells and germ cells, including the spermatozoa in the interstitial space and the seminiferous tubule compartments. We profiled the proteome of testicular EVs and probed the cell types that release them, revealing the potential contributions from the Leydig cells and testicular macrophages. Moreover, we sequenced the small RNA cargoes of testicular EVs and identified sets of small non-coding RNAs that were overlooked in the testis transcriptome. Selected miRNA candidates in testicular EVs were found in sperm RNA payload and demonstrated specific resistance towards ribonuclease A independent of the vesicle membrane. Small molecule inhibition of EV secretion perturbed spermatogenesis via inter-compartmental communication.

Conclusions
Together, our study provides a valuable resource on the repertoire of cargoes carried by testicular EVs and uncovers a physiological function of testicular EVs in inter-compartmental communication associated to spermatogenesis.
Diabetic kidney disease and risk of incident stroke among adults with type 2 diabetes
Authors: Kaze Arnaud D. , Jaar Bernard G. , Fonarow Gregg C. , Echouffo-Tcheugui Justin B. 
Published: March 2022

Abstract
Background
Data on the relations between kidney function abnormalities and stroke in type 2 diabetes are limited. We evaluated the associations of kidney function abnormalities and chronic kidney disease (CKD) stages with incident stroke in a large sample of adults with type 2 diabetes.

Methods
Participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study without history of stroke at baseline were included. Urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were assessed at baseline. CKD categories were defined according to the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) for stroke in relation to measures of kidney function and CKD categories.

Results
A total of 9170 participants (mean age 62.8 [SD: 6.6] years, 38.2% women, 62.9% white) were included. Over a median follow-up of 4.9 years (interquartile range: 4.0–5.7), 156 participants developed a stroke (incidence rate 3.6/1000 person-years [95% CI 3.0–4.2]). After adjusting for relevant confounders, higher UACR and lower eGFR were each associated with increased risk of stroke. Compared to UACR < 30 mg/g, moderate albuminuria and severe albuminuria were associated with increasing hazards for stroke (HR 1.61 [95% CI 1.12–2.32] and 2.29 [95% CI 1.39–3.80], respectively). Compared to eGFR of ≥ 60 mL/min/1.73 m2, decreased eGFR (eGFR < 60 mL/min/1.73 m2) was associated with higher risk of stroke (HR 1.50, 95% CI 0.98–2.29). Compared to no CKD, worsening CKD stage was associated with an increasing risk of stroke (HRs of 1.76 [95% CI 1.10–2.83] for CKD G1, 1.77 [95% CI 1.13–2.75] for CKD G2, and 2.03 [95% CI 1.27–3.24] for CKD G3).

Conclusions
In a large sample of adults with type 2 diabetes, increasing albuminuria and worsening stages of early CKD were independently associated with higher risk of incident stroke.

Trial registration
ClinicalTrials.gov. Identifier: NCT00000620.
Chimeric virus-like particles presenting tumour-associated MUC1 epitope result in high titers of specific IgG antibodies in the presence of squalene oil-in-water adjuvant: towards safe cancer immunotherapy
Authors: Panasiuk Mirosława , Zimmer Karolina , Czarnota Anna , Narajczyk Magdalena , Peszyńska-Sularz Grażyna , Chraniuk Milena , Hovhannisyan Lilit , Żołędowska Sabina , Nidzworski Dawid , Żaczek Anna J. , Gromadzka Beata 
Published: March 2022

Abstract
Background
Immunotherapy is emerging as a powerful treatment approach for several types of cancers. Modulating the immune system to specifically target cancer cells while sparing healthy cells, is a very promising approach for safer therapies and increased survival of cancer patients. Tumour-associated antigens are favorable targets for cancer immunotherapy, as they are exclusively expressed by the cancer cells, minimizing the risk of an autoimmune reaction. The ability to initiate the activation of the immune system can be achieved by virus-like particles (VLPs) which are safe and potent delivery tools. VLP‐based vaccines have evolved dramatically over the last few decades and showed great potential in preventing infectious diseases. Immunogenic potency of engineered VLPs as a platform for the development of effective therapeutic cancer vaccines has been studied extensively. This study involves recombinant VLPs presenting multiple copies of tumour-specific mucin 1 (MUC1) epitope as a potentially powerful tool for future immunotherapy.

Results
In this report VLPs based on the structural protein of Norovirus (NoV VP1) were genetically modified to present multiple copies of tumour-specific MUC1 epitope on their surface. Chimeric MUC1 particles were produced in the eukaryotic Leishmania tarentolae expression system and used in combination with squalene oil-in-water emulsion MF59 adjuvant to immunize BALB/c mice. Sera from vaccinated mice demonstrated high titers of IgG and IgM antibodies which were specifically recognizing MUC1 antigen.

Conclusions
The obtained results show that immunization with recombinant chimeric NoV VP1- MUC1 VLPs result in high titers of MUC1 specific IgG antibodies and show great therapeutic potential as a platform to present tumour-associated antigens.

Graphical Abstract
Comparative efficacy of bio-selenium nanoparticles and sodium selenite on morpho-physiochemical attributes under normal and salt stress conditions, besides selenium detoxification pathways in Brassica napus L.
Authors: El-Badri Ali Mahmoud , Hashem Ahmed M. , Batool Maria , Sherif Ahmed , Nishawy Elsayed , Ayaad Mohammed , Hassan Hamada M. , Elrewainy Ibrahim M. , Wang Jing , Kuai Jie , Wang Bo , Zheng Shixue , Zhou Guangsheng 
Published: March 2022

AbstractSelenium nanoparticles (SeNPs) have attracted considerable attention globally due to their significant potential for alleviating abiotic stresses in plants. Accordingly, further research has been conducted to develop nanoparticles using chemical ways. However, our knowledge about the potential benefit or phytotoxicity of bioSeNPs in rapeseed is still unclear. Herein, we investigated the effect of bioSeNPs on growth and physiochemical attributes, and selenium detoxification pathways compared to sodium selenite (Se (IV)) during the early seedling stage under normal and salt stress conditions. Our findings showed that the range between optimal and toxic levels of bioSeNPs was wider than Se (IV), which increased the plant’s ability to reduce salinity-induced oxidative stress. BioSeNPs improved the phenotypic characteristics of rapeseed seedlings without the sign of toxicity, markedly elevated germination, growth, photosynthetic efficiency and osmolyte accumulation versus Se (IV) under normal and salt stress conditions. In addition to modulation of Na+ and K+ uptake, bioSeNPs minimized the ROS level and MDA content by activating the antioxidant enzymes engaged in ROS detoxification by regulating these enzyme-related genes expression patterns. Importantly, the main effect of bioSeNPs and Se (IV) on plant growth appeared to be correlated with the change in the expression levels of Se-related genes. Our qRT-PCR results revealed that the genes involved in Se detoxification in root tissue were upregulated upon Se (IV) treated seedlings compared to NPs, indicating that bioSeNPs have a slightly toxic effect under higher concentrations. Furthermore, bioSeNPs might improve lateral root production by increasing the expression level of LBD16. Taken together, transamination and selenation were more functional methods of Se detoxification and proposed different degradation pathways that synthesized malformed or deformed selenoproteins, which provided essential mechanisms to increase Se tolerance at higher concentrations in rapeseed seedlings. Current findings could add more knowledge regarding the mechanisms underlying bioSeNPs induced plant growth.
Graphical Abstract
Hydroxychloroquine attenuates neuroinflammation following traumatic brain injury by regulating the TLR4/NF-κB signaling pathway
Authors: Hu Jian , Wang Xue , Chen Xiongjian , Fang Yani , Chen Kun , Peng Wenshuo , Wang Zhengyi , Guo Kaiming , Tan Xianxi , Liang Fei , Lin Li , Xiong Ye 
Published: March 2022

Abstract
Background
After traumatic brain injury (TBI), an acute, robust inflammatory cascade occurs that is characterized by the activation of resident cells such as microglia, the migration and recruitment of peripheral immune cells and the release of inflammatory mediators that induce secondary cell death and impede neurological recovery. In addition, neuroinflammation can alter blood–brain barrier (BBB) permeability. Controlling inflammatory responses is considered a promising therapeutic approach for TBI. Hydroxychloroquine (HCQ) has already been used clinically for decades, and it is still widely used to treat various autoimmune diseases. However, the effects of HCQ on inflammation and the potential mechanism after TBI remain to be defined. The aim of the current study was to elucidate whether HCQ could improve the neurological recovery of mice post-TBI by inhibiting the inflammatory response via the TLR4/NF-κB signaling pathway.

Methods
C57BL/6 mice were subjected to controlled cortical impact (CCI) and randomly divided into groups that received intraperitoneal HCQ or vehicle daily after TBI. TAK-242 (3.0 mg/kg), an exogenous TLR4 antagonist, was injected intraperitoneally 1 h before TBI. Behavioral assessments were performed on days 1 and 3 post-TBI, and the gene expression levels of inflammatory cytokines were analyzed by qRT-PCR. The presence of infiltrated immune cells was examined by flow cytometry and immunostaining. In addition, BBB permeability, tight junction expression and brain edema were investigated.

Results
HCQ administration significantly ameliorated TBI-induced neurological deficits. HCQ alleviated neuroinflammation, the activation and accumulation of microglia and immune cell infiltration in the brain, attenuated BBB disruption and brain edema, and upregulated tight junction expression. Combined administration of HCQ and TAK-242 did not enhance the neuroprotective effects of HCQ.

Conclusions
HCQ reduced proinflammatory cytokine expression, and the underlying mechanism may involve suppressing the TLR4/NF-κB signaling pathway, suggesting that HCQ is a potential therapeutic agent for TBI treatment.
Integrative analyses of genes related to femoral head osteonecrosis: an umbrella review of systematic reviews and meta-analyses of observational studies
Authors: Lee Sangyeob , Yoo Jun-Il , Kang Yang-Jae 
Published: March 2022

Abstract
Background
Femoral head osteonecrosis (FHON) is a worldwide challenging clinical topic. Steroid use is one of the main etiologies of FHON. There are several genetic variants associated with FHON. Therefore, the purpose of this umbrella review was to provide a comprehensive summary of a meta-analysis and systematic review of genetic variations associated with nonsteroidal and steroid-induced FHON.

Methods
The eligible studies were selected from the PubMed and MEDLINE databases for the collection of diverse systematic meta-analyses and reviews. The genetic main effect score was assigned using the Human Genome Epidemiology Network’s Venice criteria to assess the cumulative evidence on the effects of a single nucleotide polymorphism (SNP) on FHON.

Results
Eight articles reported the meta-analysis of candidate SNP-based studies covering eight genes and 13 genetic variants. In the nonsteroid-induced FHON genetic variants including rs2012390 and rs11225394 in MMP8, rs1800629 and rs361525 in tumor necrosis factor (TNF)-α, VNTR in intron 4, rs1799983 and rs2070744 in endothelial nitric oxide synthase (eNOS), rs2010963 in vascular endothelial growth factor (VEGF), and rs6025 in factor V showed significance in each reference. The steroid-induced FHON genetic variants including rs693 and rs1042031 in apolipoprotein (Apo)B, rs1045642 in ABCB1, and rs1799889 in PAI-1 showed significance in each reference.

Conclusion
Based on the systematic review conducted in this study, we organized the genomes associated with FHON and looked at each contribution. Our results could give an integrative approach for understanding the mechanism of FHON etiology. It is expected that these results could contribute to the strategy of prediagnosis, evaluating the individual risk of nonsteroid-induced and steroid-induced FHON.

Level of Evidence: Level I.
Postpartum depression in maternal thyroidal changes
Authors: Schmidt Paula Michele da Silva , Longoni Aline , Pinheiro Ricardo Tavares , Assis Adriano Martimbianco de 
Published: March 2022

AbstractEvidence in the literature has suggested that there may be an association between thyroid antibodies and depression during pregnancy and in the postpartum period. Thus, this study aims to conduct a systematic review on the prevalence of postpartum depression (PPD) in women with thyroid abnormalities during pregnancy or in the postpartum period. For this review, we used four databases (PubMed, Lilacs, Scielo, and Scopus). Fifteen studies were selected; one study used a case–control design, four used a cross-sectional design and ten utilized prospective cohort designs. All studies were restricted to up to 1 year postpartum, and 46.7% focused on a period between immediate postpartum and 6 months postpartum. Estimates of the prevalence of PPD in pregnant women with thyroid disorders ranged between 8.3% and 36.0%. For follow-up studies, the cumulative incidence of self-reported depression from the primary episode in the first postpartum year was 6.3% in a high-city survey. Although some authors consider the status of positive anti-TPO antibodies to be a possible marker of vulnerability to depression , it is not yet possible to conclude whether thyroid function in the pregnancy-puerperal cycle is involved with the development of PPD.
Non-medical factors in prehospital resuscitation decision-making: a mixed-methods systematic review
Authors: Milling Louise , Kjær Jeannett , Binderup Lars Grassmé , de Muckadell Caroline Schaffalitzky , Havshøj Ulrik , Christensen Helle Collatz , Christensen Erika Frischknecht , Lassen Annmarie Touborg , Mikkelsen Søren , Nielsen Dorthe 
Published: March 2022

AbstractAimThis systematic review explored how non-medical factors influence the prehospital resuscitation providers’ decisions whether or not to resuscitate adult patients with cardiac arrest.MethodsWe conducted a mixed-methods systematic review with a narrative synthesis and searched for original quantitative, qualitative, and mixed-methods studies on non-medical factors influencing resuscitation of out-of-hospital cardiac arrest. Mixed-method reviews combine qualitative, quantitative, and mixed-method studies to answer complex multidisciplinary questions. Our inclusion criteria were peer-reviewed empirical-based studies concerning decision-making in prehospital resuscitation of adults > 18 years combined with non-medical factors. We excluded commentaries, case reports, editorials, and systematic reviews. After screening and full-text review, we undertook a sequential exploratory synthesis of the included studies, where qualitative data were synthesised first followed by a synthesis of the quantitative findings.ResultsWe screened 15,693 studies, reviewed 163 full-text studies, and included 27 papers (12 qualitative, two mixed-method, and 13 quantitative papers). We identified five main themes and 13 subthemes related to decision-making in prehospital resuscitation. Especially the patient’s characteristics and the ethical aspects were included in decisions concerning resuscitation. The wishes and emotions of bystanders further influenced the decision-making. The prehospital resuscitation providers’ characteristics, experiences, emotions, values, and team interactions affected decision-making, as did external factors such as the emergency medical service system and the work environment, the legislation, and the cardiac arrest setting. Lastly, prehospital resuscitation providers’ had to navigate conflicts between jurisdiction and guidelines, and conflicting values and interests.ConclusionsOur findings underline the complexity in prehospital resuscitation decision-making and highlight the need for further research on non-medical factors in out-of-hospital cardiac arrest.