bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mixed-methods study describing behavioral factors that influenced general practitioners’ experiences using triage during the COVID-19 pandemic
Authors: Lackey Shaun , Schmidtke Kelly Ann , Vlaev Ivo 
Published: July 2021

Abstract
Background
Early in the COVID-19 pandemic, general practices were asked to expand triage and to reduce unnecessary face-to-face contact by prioritizing other consultation modes, e.g., online messaging, video, or telephone. The current study explores the potential barriers and facilitators general practitioners experienced to expanding triage systems and their attitudes towards triage during the COVID-19 pandemic.

Method
A mixed-method study design was used in which a quantitative online survey was conducted along with qualitative interviews to gain a more nuanced appreciation for practitioners’ experiences in the United Kingdom. The survey items were informed by the Theoretical Domains Framework so they would capture 14 behavioral factors that may influence whether practitioners use triage systems. Items were responded to using seven-point Likert scales. A median score was calculated for each item. The responses of participants identifying as part-owners and non-owners (i.e., “partner” vs. “non-partner” practitioners) were compared. The semi-structured interviews were conducted remotely and examined using Braun and Clark’s thematic analysis.

Results
The survey was completed by 204 participants (66% Female). Most participants (83%) reported triaging patients. The items with the highest median scores captured the ‘Knowledge,’ ‘Skills,’ ‘Social/Professional role and identity,’ and ‘Beliefs about capabilities’ domains. The items with the lowest median scores captured the ‘Beliefs about consequences,’ ‘Goals,’ and ‘Emotions’ domains. For 14 of the 17 items, partner scores were higher than non-partner scores. All the qualitative interview participants relied on a phone triage system. Six broad themes were discovered: patient accessibility, confusions around what triage is, uncertainty and risk, relationships between service providers, job satisfaction, and the potential for total digital triage. Suggestions arose to optimize triage, such as ensuring there is sufficient time to conduct triage accurately and providing practical training to use triage efficiently.

Conclusions
Many general practitioners are engaging with expanded triage systems, though more support is needed to achieve total triage across practices. Non-partner practitioners likely require more support to use the triage systems that practices take up. Additionally, practical support should be made available to help all practitioners manage the new risks and uncertainties they are likely to experience during non-face-to-face consultations.
How one treats lateral epicondylitis – a survey among Brazilian orthopedists
Authors: Lazarini Rafael Fuchs , Zan Renato Arouca , Belloti João Carlos , de Almeida Filho Ildeu Afonso , Centenaro Luiz Fernando Sartori , Matsunaga Fabio Teruo , Tamaoki Marcel Jun Sugawara 
Published: July 2021

Abstract
Background
Lateral epicondylitis (LE), also known as tennis elbow, is the most common painful elbow condition. It affects approximately 1–3% of adults. There are various possible treatments described in the literature, but evidence to support a gold standard management protocol is lacking. Therefore, the objective of this study was to evaluate how Brazilian orthopaedists diagnose and treat lateral epicondylitis and compare these results with the available evidence.

Methods
This is an observational, analytical, cross-sectional study. A questionnaire was prepared to obtain information from the participants with eight specific questions (2 on diagnosis and 6 on treatment). These questions were answered voluntarily by participants at 3 major congresses of orthopaedists in Brazil in 2018. The results were analysed in accordance with the overall number of responses and were evaluated among groups according to subspecialty.

Results
We obtained a total of 501 questionnaires. Of these, 33 were excluded. The mean age was 38.67 years. The majority of respondents (91%) were male. We obtained 26.7% from specialists in hand surgery (Hand group), 36.5% from subspecialists in shoulder and elbow (Shoulder and Elbow group), and 36.8% from generalists in orthopaedics or from other subspecialties (General Orthopaedists group). For diagnosis, 24.4% did not initially request any imaging method. The most requested exam was ultrasonography (54.9%). The most prominent indication for initial treatment was physical therapy. For refractory cases, 78.3% of the respondents preferred doing a local infiltration. The most commonly used substance for local infiltrations was corticosteroids (89.6%). With respect to the surgical treatment option, 75.8% of those who recommend it prefer open techniques, and 24.2% prefer arthroscopic treatment. Of the total respondents, 12.8% did not recommend surgical treatment for LE.

Conclusion
Among Brazilian orthopaedists, the Cozen test is most frequently chosen, and ultrasound is the most commonly used imaging tool. Nonsurgically, oral nonsteroidal anti-inflammatory drugs (NSAIDs) plus physiotherapy is the most popular initial therapy, and corticosteroids are the most popular type of infiltration agent. Most surgeons recommended surgery after 6 months of nonsurgical treatment, and 75.8% preferred the open technique.
Protectin conjugates in tissue regeneration 1 restores lipopolysaccharide-induced pulmonary endothelial glycocalyx loss via ALX/SIRT1/NF-kappa B axis
Authors: Wang Xin-Yang , Li Xin-Yu , Wu Cheng-Hua , Hao Yu , Fu Pan-Han , Mei Hong-Xia , Chen Fang , Gong Yu-Qiang , Jin Sheng-Wei , Li Hui 
Published: July 2021

Abstract
Background
Endothelial glycocalyx loss is integral to increased pulmonary vascular permeability in sepsis-related acute lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel macrophage-derived lipid mediator exhibiting potential anti-inflammatory and pro-resolving benefits.

Methods
PCTR1 was administrated intraperitoneally with 100 ng/mouse after lipopolysaccharide (LPS) challenged. Survival rate and lung function were used to evaluate the protective effects of PCTR1. Lung inflammation response was observed by morphology and inflammatory cytokines level. Endothelial glycocalyx and its related key enzymes were measured by immunofluorescence, ELISA, and Western blot. Afterward, related-pathways inhibitors were used to identify the mechanism of endothelial glycocalyx response to PCTR1 in mice and human umbilical vein endothelial cells (HUVECs) after LPS administration.

Results
In vivo, we show that PCTR1 protects mice against lipopolysaccharide (LPS)-induced sepsis, as shown by enhanced the survival and pulmonary function, decreased the inflammatory response in lungs and peripheral levels of inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Moreover, PCTR1 restored lung vascular glycocalyx and reduced serum heparin sulphate (HS), syndecan-1 (SDC-1), and hyaluronic acid (HA) levels. Furthermore, we found that PCTR1 downregulated heparanase (HPA) expression to inhibit glycocalyx degradation and upregulated exostosin-1 (EXT-1) protein expression to promote glycocalyx reconstitution. Besides, we observed that BAY11-7082 blocked glycocalyx loss induced by LPS in vivo and in vitro, and BOC-2 (ALX antagonist) or EX527 (SIRT1 inhibitor) abolished the restoration of HS in response to PCTR1.

Conclusion
PCTR1 protects endothelial glycocalyx via ALX receptor by regulating SIRT1/NF-κB pathway, suggesting PCTR1 may be a significant therapeutic target for sepsis-related acute lung injury.
Multi-responsive nanofibers composite gel for local drug delivery to inhibit recurrence of glioma after operation
Authors: Zhu Yufu , Jia Jun , Zhao Gang , Huang Xuyang , Wang Lansheng , Zhang Yongkang , Zhang Long , Konduru Naveena , Xie Jun , Yu Rutong , Liu Hongmei 
Published: July 2021

Abstract
Background
The postoperative recurrence of malignant gliomas has presented a clinical conundrum currently. Worse, there is no standard treatment for these recurrent tumours. Therefore, novel promising methods of clinical treatment are urgently needed.

Methods
In this study, we synthesized reactive oxygen species (ROS)-triggered poly(propylene sulfide)60 (PPS60) mixed with matrix metalloproteinases (MMPs)-responsive triglycerol monostearate (T) lipids and TMZ. The mixed solution could self-assemble at 50 ℃ to generate hydrogels with MMPs- and ROS-responsiveness. We explored whether the T/PPS + TMZ hydrogel could achieve the MMP- and ROS-responsive delivery of TMZ and exert anti-glioma regrowth effects in vitro and in vivo. These results demonstrated that the T/PPS + TMZ hydrogel significantly improved the curative effect of TMZ to inhibit postsurgical recurrent glioma.

Results
The results confirmed the responsive release of TMZ encapsulated in the T/PPS + TMZ hydrogel, and the hydrogel showed excellent performance against glioma in an incomplete glioma operation model, which indicated that the T/PPS + TMZ hydrogel effectively inhibited the growth of recurrent glioma.

Conclusion
In summary, we successfully developed injectable MMPs- and ROS-responsive hydrogels that could achieve the sustained release of TMZ in the surgical cavity to inhibit local recurrent glioma after surgery.

Graphic abstract
Cartilage-targeting poly(ethylene glycol) (PEG)-formononetin (FMN) nanodrug for the treatment of osteoarthritis
Authors: Xiong Wei , Lan Qiumei , Liang Xiaonan , Zhao Jinmin , Huang Hanji , Zhan Yanting , Qin Zainen , Jiang Xianfang , Zheng Li 
Published: July 2021

AbstractIntra-articular (IA) injection is an efficient treatment for osteoarthritis, which will minimize systemic side effects. However, the joint experiences rapid clearance of therapeutics after intra-articular injection. Delivering system modified through active targeting strategies to facilitate localization within specific joint tissues such as cartilage is hopeful to increase the therapeutic effects. In this study, we designed a nanoscaled amphiphilic and cartilage-targeting polymer-drug delivery system by using formononetin (FMN)-poly(ethylene glycol) (PEG) (denoted as PCFMN), which was prepared by PEGylation of FMN followed by coupling with cartilage-targeting peptide (CollBP). Our results showed that PCFMN was approximately regular spherical with an average diameter about 218 nm. The in vitro test using IL-1β stimulated chondrocytes indicated that PCFMN was biocompatible and upregulated anabolic genes while simultaneously downregulated catabolic genes of the articular cartilage. The therapeutic effects in vivo indicated that PCFMN could effectively attenuate the progression of OA as evidenced by immunohistochemical staining and histological analysis. In addition, PCFMN showed higher intention time in joints and better anti-inflammatory effects than FMN, indicating the efficacy of cartilage targeting nanodrug on OA. This study may provide a reference for clinical OA therapy.
JMJD3: a critical epigenetic regulator in stem cell fate
Authors: Ding Yuanjie , Yao Yuanchun , Gong Xingmu , Zhuo Qi , Chen Jinhua , Tian Miao , Farzaneh Maryam 
Published: July 2021

AbstractThe Jumonji domain-containing protein-3 (JMJD3) is a histone demethylase that regulates the trimethylation of histone H3 on lysine 27 (H3K27me3). H3K27me3 is an important epigenetic event associated with transcriptional silencing. JMJD3 has been studied extensively in immune diseases, cancer, and tumor development. There is a comprehensive epigenetic transformation during the transition of embryonic stem cells (ESCs) into specialized cells or the reprogramming of somatic cells to induced pluripotent stem cells (iPSCs). Recent studies have illustrated that JMJD3 plays a major role in cell fate determination of pluripotent and multipotent stem cells (MSCs). JMJD3 has been found to enhance self-renewal ability and reduce the differentiation capacity of ESCs and MSCs. In this review, we will focus on the recent advances of JMJD3 function in stem cell fate.
ALKBH3 partner ASCC3 mediates P-body formation and selective clearance of MMS-induced 1-methyladenosine and 3-methylcytosine from mRNA
Authors: Wollen Kristian Lied , Hagen Lars , Vågbø Cathrine B. , Rabe Renana , Iveland Tobias S. , Aas Per Arne , Sharma Animesh , Sporsheim Bjørnar , Erlandsen Hilde O. , Palibrk Vuk , Bjørås Magnar , Fonseca Davi M. , Mosammaparast Nima , Slupphaug Geir 
Published: July 2021

AbstractBackgroundReversible enzymatic methylation of mammalian mRNA is widespread and serves crucial regulatory functions, but little is known to what degree chemical alkylators mediate overlapping modifications and whether cells distinguish aberrant from canonical methylations.MethodsHere we use quantitative mass spectrometry to determine the fate of chemically induced methylbases in the mRNA of human cells. Concomitant alteration in the mRNA binding proteome was analyzed by SILAC mass spectrometry.ResultsMMS induced prominent direct mRNA methylations that were chemically identical to endogenous methylbases. Transient loss of 40S ribosomal proteins from isolated mRNA suggests that aberrant methylbases mediate arrested translational initiation and potentially also no-go decay of the affected mRNA. Four proteins (ASCC3, YTHDC2, TRIM25 and GEMIN5) displayed increased mRNA binding after MMS treatment. ASCC3 is a binding partner of the DNA/RNA demethylase ALKBH3 and was recently shown to promote disassembly of collided ribosomes as part of the ribosome quality control (RQC) trigger complex. We find that ASCC3-deficient cells display delayed removal of MMS-induced 1-methyladenosine (m1A) and 3-methylcytosine (m3C) from mRNA and impaired formation of MMS-induced P-bodies.ConclusionsOur findings conform to a model in which ASCC3-mediated disassembly of collided ribosomes allows demethylation of aberrant m1A and m3C by ALKBH3. Our findings constitute first evidence of selective sanitation of aberrant mRNA methylbases over their endogenous counterparts and warrant further studies on RNA-mediated effects of chemical alkylators commonly used in the clinic.
Alterations in intermuscular coordination underlying isokinetic exercise after a stroke and their implications on neurorehabilitation
Authors: Park Jeong-Ho , Shin Joon-Ho , Lee Hangil , Roh Jinsook , Park Hyung-Soon 
Published: July 2021

Abstract
Background
Abnormal intermuscular coordination limits the motor capability of stroke-affected upper limbs. By evaluating the intermuscular coordination in the affected limb under various biomechanical task constraints, the impact of a stroke on motor control can be analyzed and intermuscular coordination-based rehabilitation strategies can be developed. In this study, we investigated upper limb intermuscular coordination after a stroke during isokinetic movements.

Methods
Sixteen chronic stroke survivors and eight neurologically intact individuals were recruited. End-point forces and electromyographic activities of the shoulder and elbow muscles were measured while the participants performed isokinetic upper limb movements in a three-dimensional space. Intermuscular coordination of the stroke survivors and the control participants was quantified in the form of muscle synergies. Then, we compared the number, composition, and activation coefficients of muscle synergies and the end-point force between the groups. The correlation between the alteration of muscle synergies and the level of motor impairment was investigated.

Results
Four and five muscle synergies in the stroke and control groups were observed, respectively. The composition of muscle synergies was comparable between the groups, except that the three heads of the deltoid muscle were co-activated and formed one synergy in the stroke group, whereas those muscles formed two synergies in the control group. When the number of muscle synergies between the groups matched, the comparable composition of muscle synergies was observed in both groups. Alternatively, the modulation of synergy activation coefficients was altered after a stroke. The severity of motor impairments was negatively correlated with the similarity of the post-stroke synergies with respect to the mean control synergies.

Conclusions
Stroke-affected upper limbs seemed to modularize the activation of the shoulder and elbow muscles in a fairly similar way to that of neurologically intact individuals during isokinetic movements. Compared with free (i.e., unconstrained) movement, exercise under biomechanical constraints including the isokinetic constraint might promote the activation of muscle synergies independently in stroke survivors. We postulated the effect of biomechanical constraints on the intermuscular coordination and suggested a possible intermuscular coordination-based rehabilitation protocol that provides the biomechanical constraint appropriate to a trainee throughout the progress of rehabilitation.
Key factors to facilitate locally driven family planning programming: a qualitative analysis of urban stakeholder perspectives in Africa and Asia
Authors: Mwaikambo Lisa , Brittingham Sarah , Ohkubo Saori , Salem Ruwaida , Sama Denis Joel , Sow Fatimata , Mathur Deepti , Anieto Nneoma Nonyelum 
Published: July 2021

Abstract
Background
There has been greater recognition of the importance of country ownership in global health and development. However, operationalising country ownership to ensure the scale up and sustainability of proven interventions remains elusive at best. To address this challenge, we undertook a thematic analysis of interviews collected from representatives of local governments, public health systems, and communities in poor urban areas of East Africa, Francophone West Africa, India, and Nigeria, supported by The Challenge Initiative (TCI), aiming to rapidly and sustainably scale up evidence-based reproductive health and family planning solutions.

Methods
The main objective of this study was to explore critical elements needed for implementing and scaling evidence-based family planning interventions. The research team conducted thematic analysis of 96 stories collected using the Most Significant Change (MSC) technique between July 2018 and September 2019. After generating 55 unique codes, the codes were grouped into related themes, using TCI’s model as a general analytical framework.

Results
Five key themes emerged: (1) strengthening local capacity and improving broader health systems, (2) shifting mindsets of government and community toward local ownership, (3) institutionalising the interventions within existing government structures, (4) improving data demand and use for better planning of health services, and (5) enhancing coordination of partners.

Conclusion
While some themes feature more prominently in a particular region than others, taken together they represent what stakeholders perceive to be essential elements for scaling up locally-driven health programmes in urban areas in Africa and Asia.
A highly efficient regeneration, genetic transformation system and induction of targeted mutations using CRISPR/Cas9 in Lycium ruthenicum
Authors: Wang Wang , Liu Jiangmiao , Wang Hai , Li Tong , Zhao Huien 
Published: July 2021

Abstract
Background
CRISPR/Cas9 is a rapidly developing genome editing technology in various biological systems due to its efficiency, portability, simplicity and versatility. This editing technology has been successfully applied in in several important plants of Solanaceae such as tomato, tobacco, potato, petunia and groundcherry. Wolfberry ranked the sixth among solanaceous crops of outstanding importance in China following potato, tomato, eggplant, pepper and tobacco. To date, there has been no report on CRISPR/Cas9 technology to improve Lycium ruthenicum due to the unknown genome sequencing and the lack of efficient regeneration and genetic transformation systems.

Results
In this study, we have established an efficientregeneration and genetic transformation system of Lycium ruthenicum. We have used this system to validate target sites for fw2.2, a major fruit weight quantitative trait locus first identified from tomato and accounted for 30% of the variation in fruit size. In our experiments, the editing efficiency was very high, with 95.45% of the transgenic lines containing mutations in the fw2.2 target site. We obtained transgenic wolfberry plants containing four homozygous mutations and nine biallelic mutations in the fw2.2 gene.

Conclusions
These results suggest that CRISPR-based gene editing is effective for the improvement of black wolfberry traits, and we expect this approach to be routinely applied to this important economic fruit.
Quantitative parameters of lymphocyte nuclear morphology in bronchoalveolar lavage fluid as novel biomarkers for sarcoidosis
Authors: Horimasu Yasushi , Yamaguchi Kakuhiro , Sakamoto Shinjiro , Masuda Takeshi , Miyamoto Shintaro , Nakashima Taku , Iwamoto Hiroshi , Fujitaka Kazunori , Hamada Hironobu , Hattori Noboru 
Published: July 2021

Abstract
Background
Bronchoalveolar lavage (BAL) is one of the fundamental examinations for the differential diagnosis of interstitial lung diseases (ILDs), and lymphocytosis strongly indicates alternative diagnoses rather than idiopathic pulmonary fibrosis. However, the BALF lymphocytosis is observed in several ILDs. We considered that quantitative evaluation of the BALF lymphocyte nuclear morphology would be useful in the differential diagnosis of ILDs with increased BALF lymphocyte fraction.

Results
One hundred and twenty-one patients with ILDs having increased BALF lymphocyte fraction were recruited (68 in the development cohort and 53 in the validation cohort). In the development cohort, BALF lymphocyte nuclei in sarcoidosis patients showed significantly smaller areas, shorter perimeters, lower radius ratios, and increased roundness than those of other ILD patients (p < 0.001 for each). Next, the fractions of lymphocytes with small areas, short perimeters, low radius ratios, and increased roundness, which were determined based on receiver operating characteristic (ROC) analyses-based thresholds, were demonstrated to be higher in sarcoidosis patients than in the other ILD patients (p < 0.001 for each). Furthermore, when we combined size-representing parameters with shape-representing parameters, the fraction of lymphocytes with small and round nuclei showed approximately 0.90 of area under the ROC curve in discriminating sarcoidosis both in the development cohort and the validation cohort.

Conclusion
This study is the first to demonstrate the usefulness of quantitative parameters of BALF lymphocyte nuclear morphology as novel biomarkers for sarcoidosis.