bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of a proactive referral tool for child healthcare professionals to encourage and facilitate parental smoking cessation in the Netherlands: a mixed-methods study
Authors: Scheffers-van Schayck Tessa , Hipple Walters Bethany , Otten Roy , Kleinjan Marloes 
Published: September 2021

AbstractBackgroundRecently, the parent-tailored telephone based smoking cessation counseling program ‘Smoke-free Parents’ was shown to be effective in helping parents to quit smoking. To implement this program in child healthcare settings in the Netherlands, the research team developed a proactive referral tool to refer parents to Smoke-free Parents. The aim of the present implementation study was to explore the facilitators, barriers, and suggestions for improvement in the implementation of this referral tool.MethodsChild healthcare professionals (N = 68) were recruited via multiple strategies (e.g., social media, mailings, and word of mouth among healthcare professionals) and invited to complete two online (quantitative and qualitative) questionnaires and to participate in a telephone semi-structured qualitative interview between April 2017 and February 2019. In total, 65 child healthcare professionals were included in the analyses. After inductive coding, thematic analyses were performed on the qualitative data. Descriptive analyses were performed on the quantitative data.ResultsThe data from both questionnaires and the telephone interview revealed that the majority of the child healthcare professionals (92.3 % female; average years of working as a healthcare professional: 23.0) found the Smoke-free Parents referral tool accessible and convenient to use. Yet there were several barriers that limited their use of the tool. The data revealed that one of the main barriers that healthcare professionals experienced was parental resistance to smoking cessation assistance. In addition, healthcare professionals noted that they experienced tension when motivating parents to quit smoking, as they were not the parent’s, but the child’s healthcare provider. Additionally, healthcare professionals reported being concerned about the lack of information about the costs of Smoke-free Parents, which limited professionals referring parents to the service.ConclusionsAlthough healthcare professionals reported rather positive experiences with the Smoke-free Parents referral tool, the use of the tool was limited due to barriers. To increase the impact of the Smoke-free Parents telephone-based smoking cessation counseling program via child healthcare settings, it is important to overcome these barriers. Suggestions for improvement in the implementation of the referral tool in child healthcare settings are discussed.
Implementation of social needs screening in primary care: a qualitative study using the health equity implementation framework
Authors: Drake Connor , Batchelder Heather , Lian Tyler , Cannady Meagan , Weinberger Morris , Eisenson Howard , Esmaili Emily , Lewinski Allison , Zullig Leah L. , Haley Amber , Edelman David , Shea Christopher M. 
Published: September 2021

AbstractBackgroundScreening in primary care for unmet individual social needs (e.g., housing instability, food insecurity, unemployment, social isolation) is critical to addressing their deleterious effects on patients’ health outcomes. To our knowledge, this is the first study to apply an implementation science framework to identify implementation factors and best practices for social needs screening and response.MethodsGuided by the Health Equity Implementation Framework (HEIF), we collected qualitative data from clinicians and patients to evaluate barriers and facilitators to implementing the Protocol for Responding to and Assessing Patients’ Assets, Risks, and Experiences (PRAPARE), a standardized social needs screening and response protocol, in a federally qualified health center. Eligible patients who received the PRAPARE as a standard of care were invited to participate in semi-structured interviews. We also obtained front-line clinician perspectives in a semi-structured focus group. HEIF domains informed a directed content analysis.ResultsPatients and clinicians (i.e., case managers) reported implementation barriers and facilitators across multiple domains (e.g., clinical encounters, patient and provider factors, inner context, outer context, and societal influence). Implementation barriers included structural and policy level determinants related to resource availability, discrimination, and administrative burden. Facilitators included evidence-based clinical techniques for shared decision making (e.g., motivational interviewing), team-based staffing models, and beliefs related to alignment of the PRAPARE with patient-centered care. We found high levels of patient acceptability and opportunities for adaptation to increase equitable adoption and reach.ConclusionOur results provide practical insight into the implementation of the PRAPARE or similar social needs screening and response protocols in primary care at the individual encounter, organizational, community, and societal levels. Future research should focus on developing discrete implementation strategies to promote social needs screening and response, and associated multisector care coordination to improve health outcomes and equity for vulnerable and marginalized patient populations.
An association study in the Taiwan Biobank elicits the GABAA receptor genes GABRB3, GABRA5, and GABRG3 as candidate loci for sleep duration in the Taiwanese population
Authors: Hou Sheue-Jane , Tsai Shih-Jen , Kuo Po-Hsiu , Lin Wan-Yu , Liu Yu-Li , Yang Albert C. , Lin Eugene , Lan Tsuo-Hung 
Published: September 2021

Abstract
Background
Gamma-aminobutyric acid type A (GABAA) receptors mainly mediate the effects of gamma-aminobutyric acid, which is the primary inhibitory neurotransmitter in the central nervous system. Abundant evidence suggests that GABAA receptors play a key role in sleep-regulating processes. No genetic association study has explored the relationships between GABAA receptor genes and sleep duration, sleep quality, and sleep timing in humans.

Methods
We determined the association between single-nucleotide polymorphisms (SNPs) in the GABAA receptor genes GABRA1, GABRA2, GABRB3, GABRA5, and GABRG3 and sleep duration, sleep quality, and sleep timing in the Taiwan Biobank with a sample of 10,127 Taiwanese subjects. There were 10,142 subjects in the original study cohort. We excluded 15 subjects with a medication history of sedative-hypnotics.

Results
Our data revealed an association of the GABRB3-GABRA5-GABRG3 gene cluster with sleep duration, which has not been previously identified: rs79333046 (beta = − 0.07; P = 1.21 × 10–3) in GABRB3, rs189790076 (beta = 0.92; P = 1.04 × 10–3) in GABRA5, and rs147619342 (beta = − 0.72; P = 3.97 × 10–3) in GABRG3. The association between rs189790076 in GABRA5 and sleep duration remained significant after Bonferroni correction. A variant (rs12438141) in GABRB3 was also found to act as a potential expression quantitative trait locus. Additionally, we discovered interactions between variants in the GABRB3-GABRA5-GABRG3 gene cluster and lifestyle factors, such as tea and coffee consumption, smoking, and physical activity, that influenced sleep duration, although some interactions became nonsignificant after Bonferroni correction. We also found interactions among GABRB3, GABRA5, and GABRG3 that affected sleep duration. Furthermore, we identified an association of rs7165524 (beta = − 0.06; P = 2.20 × 10–3) in GABRA5 with sleep quality and an association of rs79465949 (beta = − 0.12; P = 3.95 × 10–3) in GABRB3 with sleep timing, although these associations became nonsignificant after Bonferroni correction. However, we detected no evidence of an association of individual SNPs in GABRA1 and GABRA2.

Conclusions
Our results indicate that rs189790076 in GABRA5 and gene–gene interactions among GABRB3, GABRA5, and GABRG3 may contribute to sleep duration in the Taiwanese population.
Pathological cytomorphologic features and the percentage of ALK FISH-positive cells predict pulmonary adenocarcinoma prognosis: a prospective cohort study
Authors: Jiang Fenge , Wang Congcong , Yang Ping , Sun Ping , Liu Jiannan 
Published: September 2021

Abstract
Background
We conducted a study to explore the relationship between pathological cytomorphologic features and the percentage of anaplastic lymphoma kinase (ALK)-positive cells to better predict pulmonary adenocarcinoma prognosis with crizotinib treatment.

Patients and methods
We investigated 60 cases of patients with ALK-positive advanced or metastatic non-small cell lung cancer (NSCLC). Immunohistochemistry was performed to screen for ALK rearrangement. Fluorescence in situ hybridization (FISH) was used to detect the percentage of ALK-positive cells. The primary objectives of the study were the progression-free survival (PFS), the 3-year overall survival, and the 3-year overall survival (OS) rates. The secondary objectives of the study were the disease control rate (DCR) and the overall response rate (ORR).

Results
We compared the pathological cytomorphologic features of 60 cases of ALK-positive pulmonary adenocarcinoma, of which 21 cases were ALK-positive with signet ring cell cytomorphologic characteristics. There were statistical differences in the ORR (p = 0.019), DCR (p = 0.032), and PFS (p = 0.047) between the signet ring cell group and group without signet ring cells. Of these, 37 cases were ALK-positive with EML4 (echinoderm microtubule associated protein like 4)-ALK high percentage of positivity group. These cases benefited more from crizotinib treatment in the ORR (p = 0.046) and achieved a longer PFS (p = 0.036) compared to those with EML4-ALK low percentage of positivity group.

Conclusions
Signet ring cell cytomorphologic characteristics of pulmonary adenocarcinoma are associated with the percentage of ALK-positive cells. Signet ring cell cytomorphologic characteristics and the percentage of ALK-positive cells might predict the prognosis of pulmonary adenocarcinoma with crizotinib treatment.

Trial registration
The study was approved by the Institutional Review Board (Medical Ethics Committee of Yantai Yuhuangding Hospital). The registration number is NO.2016[193].
HSF1 is involved in suppressing A1 phenotype conversion of astrocytes following spinal cord injury in rats
Authors: Li Lilan , Li Yu , He Bingqiang , Li Hui , Ji Huiyuan , Wang Yingjie , Zhu Zhenjie , Hu Yuming , Zhou Yue , Yang Ting , Sun Chunshuai , Yuan Ying , Wang Yongjun 
Published: September 2021

AbstractBackgroundTwo activation states of reactive astrocytes termed A1 and A2 subtypes emerge at the lesion sites following spinal cord injury (SCI). A1 astrocytes are known to be neurotoxic that participate in neuropathogenesis, whereas A2 astrocytes have been assigned the neuroprotective activity. Heat shock transcription factor 1 (HSF1) plays roles in protecting cells from stress-induced apoptosis and in controlling inflammatory activation. It is unknown whether HSF1 is involved in suppressing the conversion of A1 astrocytes following SCI.MethodsA contusion model of the rat spinal cord was established, and the correlations between HSF1 expression and onset of A1 and A2 astrocytes were assayed by Western blot and immunohistochemistry. 17-AAG, the agonist of HSF1, was employed to treat the primary cultured astrocytes following a challenge by an A1-astrocyte-conditioned medium (ACM) containing 3 ng/ml of IL-1α, 30 ng/ml of TNF-α, and 400 ng/ml of C1q for induction of the A1 subtype. The effects of 17-AAG on the phenotype conversion of astrocytes, as well as underlying signal pathways, were examined by Western blot or immunohistochemistry.ResultsThe protein levels of HSF1 were significantly increased at 4 days and 7 days following rat SCI, showing colocalization with astrocytes. Meanwhile, C3-positive A1 astrocytes were observed to accumulate at lesion sites with a peak at 1 day and 4 days. Distinctively, the S100A10-positive A2 subtype reached its peak at 4 days and 7 days. Incubation of the primary astrocytes with ACM markedly induced the conversion of the A1 phenotype, whereas an addition of 17-AAG significantly suppressed such inducible effects without conversion of the A2 subtype. Activation of HSF1 remarkably inhibited the activities of MAPKs and NFκB, which was responsible for the regulation of C3 expression. Administration of 17-AAG at the lesion sites of rats was able to reduce the accumulation of A1 astrocytes.ConclusionCollectively, these data reveal a novel mechanism of astrocyte phenotype conversion following SCI, and HSF1 plays key roles in suppressing excessive increase of neurotoxic A1 astrocytes.
Effects of weekly pain monitoring on back pain outcomes: a non-randomised controlled study
Authors: Kongsted Alice , Jensen Tue Secher , Doktor Klaus , Hestbæk Lise 
Published: September 2021

Abstract
Background
Disease monitoring is an important element of self-management of several chronic diseases. Pain monitoring has become very easily available, but the role in musculoskeletal pain conditions is not clear. Awareness of pain might be helpful for people to understand pain, but focusing on pain may on the contrary negatively affect pain experience and behaviours. The objective of this study was to investigate the potential impact of pain monitoring on low back pain (LBP), specifically to determine if pain intensity, activity limitation and pain control, differed between patients with weekly pain monitoring over 12 months and patients with follow-ups at 2 weeks, 3 months and 12 months.

Methods
This was a non-randomised controlled study embedded in a cohort study with data collection November 1st 2016 to December 21st 2018. Adults seeking care for LBP were enrolled at the first visit to a chiropractor and followed with surveys after 2 weeks, 3 months and 12 months. Those enrolled first, n = 1,623, furthermore received weekly SMS-questions about pain frequency and pain intensity, whereas those enrolled next was the control group, n = 1,269 followed only by surveys. Outcomes at 12-months were compared, adjusting for group differences on baseline parameters.

Results
LBP intensity (0–10) was slightly lower at 12-months follow-up in the SMS group than the control group (adjusted beta − 0.40 (95% CI: − 0.62; − 0.19)). No relevant between-group differences were observed for activity limitation (0–100) (1.51 (95% CI: − 0.83; 3.85)) or ability to control pain (0–10) (− 0.08 (95% CI − 0.31; 0.15)).

Conclusions
Frequent pain monitoring did not demonstrate any negative effects of weekly pain monitoring, and it was perhaps even helpful. The role of self-monitoring as part of self-managing LBP should be explored further including optimal frequencies, formats, and methods for feedback.

Trial registration

The study was not registered as a clinical trial.
Creating a novel petal regeneration system for function identification of colour gene of grape hyacinth
Authors: Lou Qian , Liu Hongli , Luo Wen , Chen Kaili , Liu Yali 
Published: September 2021

Abstract
Background
Grape hyacinth (Muscari spp.) is one of the most important ornamental bulbous plants. However, its lengthy juvenile period and time-consuming transformation approaches under the available protocols impedes the functional characterisation of its genes in flower tissues. In vitro flower organogenesis has long been used to hasten the breeding cycle of plants but has not been exploited for shortening the period of gene transformation and characterisation in flowers.

Results
A petal regeneration system was established for stable transformation and function identification of colour gene in grape hyacinth. By culturing on Murashige and Skoog medium (MS) with 0.45 μM 2,4-dichlorophenoxyacetic acid (2,4-D) and 8.88 μM 6-benzyladenine (6-BA), during the colour-changing period, the flower bud explants gave rise to regeneration petals in less than 3 months, instead of the 3 years required in field-grown plants. By combining this system with Agrobacterium-mediated transformation, a glucuronidase reporter gene (GUS) was delivered into grape hyacinth petals. Ultimately, 214 transgenic petals were regenerated from 24 resistant explants. PCR and GUS quantitative analyses confirmed that these putative transgenic petals have stably overexpressed GUS genes. Furthermore, an RNAi vector of the anthocyanidin 3-O-glucosyltransferase gene (MaGT) was integrated into grape hyacinth petals using the same strategy. Compared with the non-transgenic controls, reduced expression of the MaGT occurred in all transgenic petals, which caused pigmentation loss by repressing anthocyanin accumulation.

Conclusion
The Agrobacterium transformation method via petal organogenesis of grape hyacinth took only 3–4 months to implement, and was faster and easier to perform than other gene-overexpressing or -silencing techniques that are currently available.
Open source 3D phenotyping of chickpea plant architecture across plant development
Authors: Salter William T. , Shrestha Arjina , Barbour Margaret M. 
Published: September 2021

AbstractBackgroundBeing able to accurately assess the 3D architecture of plant canopies can allow us to better estimate plant productivity and improve our understanding of underlying plant processes. This is especially true if we can monitor these traits across plant development. Photogrammetry techniques, such as structure from motion, have been shown to provide accurate 3D reconstructions of monocot crop species such as wheat and rice, yet there has been little success reconstructing crop species with smaller leaves and more complex branching architectures, such as chickpea.ResultsIn this work, we developed a low-cost 3D scanner and used an open-source data processing pipeline to assess the 3D structure of individual chickpea plants. The imaging system we developed consists of a user programmable turntable and three cameras that automatically captures 120 images of each plant and offloads these to a computer for processing. The capture process takes 5–10 min for each plant and the majority of the reconstruction process on a Windows PC is automated. Plant height and total plant surface area were validated against “ground truth” measurements, producing R2 > 0.99 and a mean absolute percentage error < 10%. We demonstrate the ability to assess several important architectural traits, including canopy volume and projected area, and estimate relative growth rate in commercial chickpea cultivars and lines from local and international breeding collections. Detailed analysis of individual reconstructions also allowed us to investigate partitioning of plant surface area, and by proxy plant biomass.ConclusionsOur results show that it is possible to use low-cost photogrammetry techniques to accurately reconstruct individual chickpea plants, a crop with a complex architecture consisting of many small leaves and a highly branching structure. We hope that our use of open-source software and low-cost hardware will encourage others to use this promising technique for more architecturally complex species.
Microwave technology: a novel approach to the transformation of natural metabolites
Authors: Hu Qi , He Yanan , Wang Fang , Wu Jing , Ci Zhimin , Chen Lumeng , Xu Runchun , Yang Ming , Lin Junzhi , Han Li , Zhang Dingkun 
Published: September 2021

AbstractMicrowave technology is used throughout the world to generate heat using energy from the microwave range of the electromagnetic spectrum. It is characterized by uniform energy transfer, low energy consumption, and rapid heating which preserves much of the nutritional value in food products. Microwave technology is widely used to process food such as drying, because food and medicinal plants are the same organisms. Microwave technology is also used to process and extract parts of plants for medicinal purposes; however, the special principle of microwave radiation provide energy to reaction for transforming chemical components, creating a variety of compounds through oxidation, hydrolysis, rearrangement, esterification, condensation and other reactions that transform original components into new ones. In this paper, the principles, influencing factors of microwave technology, and the transformation of natural metabolites using microwave technology are reviewed, with an aim to provide a theoretical basis for the further study of microwave technology in the processing of medicinal materials.
KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state
Authors: Lee Jin-Woo , Hur Jin , Kwon Yoo-Wook , Chae Cheong-Whan , Choi Jae-Il , Hwang Injoo , Yun Ji-Yeon , Kang Jin-A , Choi Young-Eun , Kim Young Hyun , Lee Sang Eun , Lee Cheol , Jo Dong Hyun , Seok Heeyoung , Cho Byong Seung , Baek Sung Hee , Kim Hyo-Soo 
Published: September 2021

Abstract
Background
Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel endogenous anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism and clinical significance.

Methods
Herein, we found Kai1 knockout mice showed significantly enhanced angiogenesis. Then, we investigated the anti-angiogenic roll of Kai1 in vitro and in vivo.

Results
KAI1 was mainly expressed in pericytes rather than in endothelial cells. It localized at the membrane surface after palmitoylation by zDHHC4 enzyme and induced LIF through the Src/p53 pathway. LIF released from pericytes in turn suppressed angiogenic factors in endothelial cells as well as in pericytes themselves, leading to inhibition of angiogenesis. Interestingly, KAI1 had another mechanism to inhibit angiogenesis: It directly bound to VEGF and PDGF and inhibited activation of their receptors. In the two different in vivo cancer models, KAI1 supplementation significantly inhibited tumor angiogenesis and growth. A peptide derived from the large extracellular loop of KAI1 has been shown to have anti-angiogenic effects to block the progression of breast cancer and retinal neovascularization in vivo.

Conclusions
KAI1 from PC is a novel molecular regulator that counterbalances the effect of angiogenic factors.
15q26 deletion in a patient with congenital heart defect, growth restriction and intellectual disability: case report and literature review
Authors: Benbouchta Yahya , De Leeuw Nicole , Amasdl Saadia , Sbiti Aziza , Smeets Dominique , Sadki Khalid , Sefiani Abdelaziz 
Published: September 2021

Abstract
Background
15q26 deletion is a relatively rare chromosomal disorder, and it is described only in few cases. Patients with this aberration show many signs and symptoms, particularly pre- and postnatal growth restriction, developmental delay, microcephaly, intellectual disability and various congenital malformations.

Case presentation
We report on a girl, 4 years old, of consanguineous parents, with a 15q26 deletion. Clinical manifestations included failure to thrive, developmental delay, microcephaly, dysmorphic facies with broad forehead, hypertelorism, narrowed eyelid slits and protruding columella. The patient also showed skeletal abnormalities, especially clinodactyly of the 5th finger, varus equine right foot and left club foot. Additionally, she had teething delay and divergent strabismus. Heart ultrasound displayed two atrial septal defects with left-to-right shunt, enlarging the right cavities. Routine cytogenetic analysis revealed a shortened 15q chromosome. Subsequent array analysis disclosed a terminal 9.15 Mb deletion at subband 15q26.1-q26.3. Four candidate genes associated with 15q26 deletion phenotype were within the deleted region, i.e. IGF1R, NR2F2, CHD2 and MEF2A.

Conclusion
We report on an additional case of 15q26 monosomy, characterized by array-CGH. Molecular cytogenetic analysis allowed us to identify the exact size of the deletion, and four candidate genes for genotype-phenotype correlation. 15q26 monosomy should be considered when growth retardation is associated with hearing anomalies and congenital heart defect, especially atrioventricular septal defects (AVSDs) and/or aortic arch anomaly (AAA).