bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examination of resident characteristics associated with interest in primary care and identification of barriers to cross-cultural care
Authors: Abrahams Sara , Kim Eun Ji , Marrast Lyndonna , Uwemedimo Omolara , Conigliaro Joseph , Martinez Johanna 
Published: April 2021

Abstract
Background
There is an increasing shortage of primary care physicians in the U.S. The difficult task of addressing patients’ sociocultural needs is one reason residents do not pursue primary care. However, associations between residents’ perceived barriers to cross-cultural care provision and career interest in primary care have not been investigated.

Objective
We examined residents’ career interest in primary care and associations with resident characteristics and their perceived barriers in providing cross-cultural care.

Methods
We conducted a cross-sectional analysis of a resident survey from the 2018–2019 academic year. We first described residents’ sociodemographic characteristics based on their career interest in primary care (Chi-square test). Our primary outcome was high career interest in primary care. We further examined associations between residents’ characteristics and perceived barriers to cross-cultural care.

Results
The study included 155 family medicine, pediatrics, and internal medicine residents (response rate 68.2%), with 17 expressing high career interest in primary care. There were significant differences in high career interest by race/ethnicity, as Non-White race was associated with high career interest in primary care (p < 0.01). Resident characteristics associated with identifying multiple barriers to cross-cultural care included disadvantaged background, multilingualism, and foreign-born parents (all p-values< 0.05). There were no significant associations between high career interest in primary care and barriers to cross-cultural care.

Conclusion
Residents from diverse racial/ethnic and socioeconomic backgrounds demonstrated higher career interest in primary care and perceived more barriers to cross-cultural care, underscoring the importance of increasing physician workforce diversity to address the primary care shortage and to improve cross-cultural care.
Compared with the monocyte to high-density lipoprotein ratio (MHR) and the neutrophil to lymphocyte ratio (NLR), the neutrophil to high-density lipoprotein ratio (NHR) is more valuable for assessing the inflammatory process in Parkinson’s disease
Authors: Liu Zhu , Fan Qingli , Wu Shizheng , Wan Yaqi , Lei Yancheng 
Published: April 2021

Abstract
Background
The inflammatory response plays essential roles in the pathological process and prognosis of Parkinson’s disease (PD). This research investigated the predictive value of the neutrophil to high-density lipoprotein ratio (NHR), neutrophil to lymphocyte ratio (NLR), and monocyte to high-density lipoprotein ratio (MHR) for PD.

Methods
Patients with PD (n = 98) were divided into three groups according to disease duration: < 6 years (n = 55), 6–10 years (n = 29) and > 10 years (n = 14). Based on the classification system of Hoehn and Yahr, grades 1 ~ 2.5 were considered early-stage PD (n = 44), and grades 3 ~ 5 were considered advanced-stage PD (n = 54). In addition, healthy subjects (n = 98) matched to the above PD patients in the same period were selected as the control group. Differences in the NHR, NLR, MHR and other indicators among the groups were evaluated.

Results
Smoking, drinking, the neutrophil count and the NHR and NLR were remarkably greater and hypertension, index of body mass, the lymphocyte count, and the levels of cholesterol in total, triglycerides, lipoprotein cholesterol with low density and uric acid were sharply lower in the PD group compared with in the control group. Analysis of multifactor logistic regression indicated that the NHR (odds ratio (adjusted OR) = 1.576, 95% CI: 1.053 ~ 2.358, P = 0.027) and NLR (adjusted OR = 1.734, 95% CI: 1.046 ~ 2.876, P = 0.033) were factors of risk for PD, while the MHR was not significantly correlated with PD. The areas under the receiver operating characteristic (ROC) curve (AUCs) for the prediction of PD by the NHR and NLR were 0.654 (95% CI: 0.583 ~ 0.721, P = 0.0001) and 0.69 (95% CI: 0.62 ~ 0.754, P < 0.0001), respectively, and the optimal cutoff values were 1.848 × 109/mmol and 2.62 × 109/mmol. Spearman’s correlation analysis indicated that the NHR was correlated with the disease duration significantly negatively and that the MHR was positively correlated with disease severity.

Conclusions
In summary, the NHR not only has strong predictive value for PD but is also closely related to disease duration. The NHR may be a better prediction for the long-period clinical results in PD patients than the MHR and NLR.

Trial registration
Clinical medical reserach center project of Qinghai Province (2017-SF-L1).
WAPL orchestrates porcine oocyte meiotic progression via control of spindle assembly checkpoint activity
Authors: Zhou Changyin , Miao Yilong , Zhang Xue , Xiong Bo 
Published: April 2021

Abstract
Background
In mitotic cells, WAPL acts as a cohesin release factor to remove cohesin complexes from chromosome arms during prophase to allow the accurate chromosome segregation in anaphase. However, we have recently documented that Wapl exerts a unique meiotic function in the spindle assembly checkpoint (SAC) control through maintaining Bub3 stability during mouse oocyte meiosis I. Whether this noncanonical function is conserved among species is still unknown.

Methods
We applied RNAi-based gene silencing approach to deplete WAPL in porcine oocytes, validating the conserved roles of WAPL in the regulation of SAC activity during mammalian oocyte maturation. We also employed immunostaining, immunoblotting and image quantification analyses to test the WAPL depletion on the meiotic progression, spindle assembly, chromosome alignment and dynamics of SAC protein in porcine oocytes.

Results
We showed that depletion of WAPL resulted in the accelerated meiotic progression by displaying the precocious polar body extrusion and compromised spindle assembly and chromosome alignment. Notably, we observed that the protein level of BUB3 was substantially reduced in WAPL-depleted oocytes, especially at kinetochores.

Conclusions
Collectively, our data demonstrate that WAPL participates in the porcine oocyte meiotic progression through maintenance of BUB3 protein levels and SAC activity. This meiotic function of WAPL in oocytes is highly conserved between pigs and mice.
Interprofessional collaboration and barriers among health and social workers caring for older adults: a Philippine case study
Authors: Moncatar TJ Robinson T. , Nakamura Keiko , Siongco Kathryn Lizbeth L. , Seino Kaoruko , Carlson Rebecca , Canila Carmelita C. , Javier Richard S. , Lorenzo Fely Marilyn E. 
Published: April 2021

Abstract
Background
There is limited information on how the barriers to interprofessional collaboration (IPC) across various professionals, organizations, and care facilities influence the health and welfare of older adults. This study aimed to describe the status of IPC practices among health and social workers providing care for older adults in the Philippines; investigate the perceived barriers to its implementation and perceived effects on geriatric care; and identify possible solutions to address the barriers limiting collaborative practice.

Methods
A case study approach was utilized employing 12 semi-structured in-depth interviews and 29 focus group discussions with care workers from selected primary health care units, public and private hospitals, and nursing homes that are directly involved in geriatric care delivery in two cities in the Philippines. Overall, 174 health and social workers consented to participate in this study. All interviews were audio-recorded and transcribed verbatim. An inductive thematic analysis using NVivo 12® was used to identify and categorize relevant thematic codes.

Results
Interprofessional geriatric care provided by health and social workers was observed to be currently limited to ad hoc communications typically addressing only administrative concerns. This limitation is imposed by a confluence of barriers such as personal values and beliefs, organizational resource constraints, and a silo system care culture which practitioners say negatively influences care delivery. This in turn results in inability of care providers to access adequate care information, as well as delays and renders inaccessible available care provided to vulnerable older adults. Uncoordinated care of older adults also led to reported inefficient duplication and overlap of interventions.

Conclusion
Geriatric care workers fear such barriers may aggravate the increasing unmet needs of older adults. In order to address these potential negative outcomes, establishing a clear and committed system of governance that includes IPC is perceived as necessary to install a cohesive service delivery mechanism and provide holistic care for older adults. Future studies are needed to measure the effects of identified barriers on the potential of IPC to facilitate an integrated health and social service delivery system for the improvement of quality of life of older adults in the Philippines.
Collective reflections on the first cycle of a collaborative learning platform to strengthen rural primary healthcare in Mpumalanga, South Africa
Authors: van der Merwe Maria , D’Ambruoso Lucia , Witter Sophie , Twine Rhian , Mabetha Denny , Hove Jennifer , Byass Peter , Tollman Stephen , Kahn Kathleen ,   the Verbal Autopsy with Participatory Action Research (VAPAR)/Wits/Mpumalanga Department of Health Learning Platform
Published: April 2021

Abstract
Background
Frontline managers and health service providers are constrained in many contexts from responding to community priorities due to organizational cultures focused on centrally defined outputs and targets. This paper presents an evaluation of the Verbal Autopsy with Participatory Action Research (VAPAR) programme—a collaborative learning platform embedded in the local health system in Mpumalanga, South Africa—for strengthening of rural primary healthcare (PHC) systems. The programme aims to address exclusion from access to health services by generating and acting on research evidence of practical, local relevance.

Methods
Drawing on existing links in the provincial and national health systems and applying rapid, participatory evaluation techniques, we evaluated the first action-learning cycle of the VAPAR programme (2017–19). We collected data in three phases: (1) 10 individual interviews with programme stakeholders, including from government departments and parastatals, nongovernmental organizations and local communities; (2) an evaluative/exploratory workshop with provincial and district Department of Health managers; and (3) feedback and discussion of findings during an interactive workshop with national child health experts.

Results
Individual programme stakeholders described early outcomes relating to effective research and stakeholder engagement, and organization and delivery of services, with potential further contributions to the establishment of an evidence base for local policy and planning, and improved health outcomes. These outcomes were verified with provincial managers. Provincial and national stakeholders identified the potential for VAPAR to support engagement between communities and health authorities for collective planning and implementation of services. Provincial stakeholders proposed that this could be achieved through a two-way integration, with VAPAR stakeholders participating in routine health planning and review activities and frontline health officials being involved in the VAPAR process. Findings were collated into a revised theory of change.

Conclusions
The VAPAR learning platform was regarded as a feasible, acceptable and relevant approach to facilitate cooperative learning and community participation in health systems. The evaluation provides support for a collaborative learning platform within routine health system processes and contributes to the limited evaluative evidence base on embedded health systems research.
Pirfenidone attenuates synovial fibrosis and postpones the progression of osteoarthritis by anti-fibrotic and anti-inflammatory properties in vivo and in vitro
Authors: Wei Qilu , Kong Ning , Liu Xiaohui , Tian Run , Jiao Ming , Li Yiyang , Guan Huanshuai , Wang Kunzheng , Yang Pei 
Published: April 2021

Abstract
Background
Osteoarthritis (OA) is a disease of the entire joint involving synovial fibrosis and inflammation. Pathological changes to the synovium can accelerate the progression of OA. Pirfenidone (PFD) is a potent anti-fibrotic drug with additional anti-inflammatory properties. However, the influence of PFD on OA is unknown.

Methods
Proliferation of human fibroblast-like synoviocytes (FLSs) after treatment with TGF-β1 or PFD was evaluated using a Cell Counting Kit-8 assay and their migration using a Transwell assay. The expression of fibrosis-related genes (COL1A1, TIMP-1, and ACTA-2) and those related to inflammation (IL-6 and TNF-α) was quantified by real-time quantitative PCR. The protein expression levels of COL1A1, α-SMA (coded by ACTA-2), IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay. A rabbit model of OA was established and then PFD was administered by gavage. The expression of genes related to fibrosis (COL1A1, TIMP-1, and ADAM-12) and inflammation (IL-6 and TNF-α) was measured using RNA extracted from the synovium. Synovial tissue was examined histologically after staining with H&E, Masson’s trichrome, and immunofluorescence. Synovitis scores, the volume fraction of collagen, and mean fluorescence intensity were calculated. Degeneration of articular cartilage was analyzed using a Safranin O-fast green stain and OARSI grading.

Results
The proliferation of FLSs was greatest when induced with 2.5 ng/ml TGF-β1 although it did not promote their migration. Therefore, 2.5 ng/ml TGF-β1 was used to stimulate the FLSs and evaluate the effects of PFD, which inhibited the migration of FLSs at concentrations as low as 1.0 mg/ml. PFD decreased the expression of COL1A1 while TGF-β1 increased both mRNA and protein expression levels of IL-6 but had no effect on α-SMA or TNF-α expression. PFD decreased mRNA expression levels of COL1A1, IL-6, and TNF-α in vivo. H&E staining and synovitis scores indicated that PFD reduced synovial inflammation, while Masson’s trichrome and immunofluorescence staining suggested that PFD decreased synovial fibrosis. Safranin O-Fast Green staining and the OARSI scores demonstrated that PFD delayed the progression of OA.

Conclusions
PFD attenuated synovial fibrosis and inflammation, and postponed the progression of osteoarthritis in a modified Hulth model of OA in rabbits, which was related to its anti-fibrotic and anti-inflammatory properties.
4R-cembranoid confers neuroprotection against LPS-induced hippocampal inflammation in mice
Authors: Rojas-Colón Luis A. , Dash Pramod K. , Morales-Vías Fabiola A. , Lebrón-Dávila Madeline , Ferchmin Pedro A. , Redell John B. , Maldonado-Martínez Geronimo , Vélez-Torres Wanda I. 
Published: April 2021

Abstract
Background
Chronic brain inflammation has been implicated in the pathogenesis of various neurodegenerative diseases and disorders. For example, overexpression of pro-inflammatory cytokines has been associated with impairments in hippocampal-dependent memory. Lipopolysaccharide (LPS) injection is a widely used model to explore the pathobiology of inflammation. LPS injection into mice causes systemic inflammation, neuronal damage, and poor memory outcomes if the inflammation is not controlled. Activation of the alpha-7 nicotinic receptor (α7) plays an anti-inflammatory role in the brain through vagal efferent nerve signaling. 4R-cembranoid (4R) is a natural compound that crosses the blood-brain barrier, induces neuronal survival, and has been shown to modulate the activity of nicotinic receptors. The purpose of this study is to determine whether 4R reduces the deleterious effects of LPS-induced neuroinflammation and whether the α7 receptor plays a role in mediating these beneficial effects.

Methods
Ex vivo population spike recordings were performed in C57BL/6J wild-type (WT) and alpha-7-knockout (α7KO) mouse hippocampal slices in the presence of 4R and nicotinic receptor inhibitors. For in vivo studies, WT and α7KO mice were injected with LPS for 2 h, followed by 4R or vehicle for 22 h. Analyses of IL-1β, TNF-α, STAT3, CREB, Akt1, and the long-term novel object recognition test (NORT) were performed for both genotypes. In addition, RNA sequencing and RT-qPCR analyses were carried out for 12 mRNAs related to neuroinflammation and their modification by 4R.

Results
4R confers neuroprotection after NMDA-induced neurotoxicity in both WT and α7KO mice. Moreover, hippocampal TNF-α and IL-1β levels were decreased with 4R treatment following LPS exposure in both strains of mice. 4R restored LPS-induced cognitive decline in NORT. There was a significant increase in the phosphorylation of STAT3, CREB, and Akt1 with 4R treatment in the WT mouse hippocampus following LPS exposure. In α7KO mice, only pAkt levels were significantly elevated in the cortex. 4R significantly upregulated mRNA levels of ORM2, GDNF, and C3 following LPS exposure. These proteins are known to play a role in modulating microglial activation, neuronal survival, and memory.

Conclusion
Our results indicate that 4R decreases the levels of pro-inflammatory cytokines; improves memory function; activates STAT3, Akt1, and CREB phosphorylation; and upregulates the mRNA levels of ORM2, GDNF, and C3. These effects are independent of the α7 nicotinic receptor.
Influences of digital media use on children and adolescents with ADHD during COVID-19 pandemic
Authors: Shuai Lan , He Shan , Zheng Hong , Wang Zhouye , Qiu Meihui , Xia Weiping , Cao Xuan , Lu Lu , Zhang Jinsong 
Published: April 2021

Abstract
Objective
To explore the influences of digital media use on the core symptoms, emotional state, life events, learning motivation, executive function (EF) and family environment of children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD) during the novel coronavirus disease 2019 (COVID-19) pandemic.

Method
A total of 192 participants aged 8–16 years who met the diagnostic criteria for ADHD were included in the study. Children scoring higher than predetermined cut-off point in self-rating questionnaires for problematic mobile phone use (SQPMPU) or Young’s internet addiction test (IAT), were defined as ADHD with problematic digital media use (PDMU), otherwise were defined as ADHD without PDMU. The differences between the two groups in ADHD symptoms, EF, anxiety and depression, stress from life events, learning motivation and family environment were compared respectively.

Results
When compared with ADHD group without PDMU, the group with PDMU showed significant worse symptoms of inattention, oppositional defiant, behavior and emotional problems by Swanson, Nolan, and Pelham Rating Scale (SNAP), more self-reported anxiety by screening child anxiety-related emotional disorders (SCARED) and depression by depression self-rating scale for children (DSRSC), more severe EF deficits by behavior rating scale of executive function (BRIEF), more stress from life events by adolescent self-rating life events checklist (ASLEC), lower learning motivation by students learning motivation scale (SLMS), and more impairment on cohesion by Chinese version of family environment scale (FES-CV). The ADHD with PDMU group spent significantly more time on both video game and social media with significantly less time spend on physical exercise as compared to the ADHD without PDMU group.

Conclusion
The ADHD children with PDMU suffered from more severe core symptoms, negative emotions, EF deficits, damage on family environment, pressure from life events, and a lower motivation to learn. Supervision of digital media usage, especially video game and social media, along with increased physical exercise, is essential to the management of core symptoms and associated problems encountered with ADHD.
Lack of the peroxiredoxin 6 gene causes impaired spatial memory and abnormal synaptic plasticity
Authors: Phasuk Sarayut , Jasmin Sureka , Pairojana Tanita , Chang Hsueh-Kai , Liang Kai-Chi , Liu Ingrid Y. 
Published: April 2021

Abstract
Peroxiredoxin 6 (PRDX6) is expressed dominantly in the astrocytes and exerts either neuroprotective or neurotoxic effects in the brain. Although PRDX6 can modulate several signaling cascades involving cognitive functions, its physiological role in spatial memory has not been investigated yet. This study aims to explore the function of the Prdx6 gene in spatial memory formation and synaptic plasticity. We first tested Prdx6−/− mice on a Morris water maze task and found that their memory performance was defective, along with reduced long-term potentiation (LTP) in CA3-CA1 hippocampal synapses recorded from hippocampal sections of home-caged mice. Surprisingly, after the probe test, these knockout mice exhibited elevated hippocampal LTP, higher phosphorylated ERK1/2 level, and decreased reactive astrocyte markers. We further reduced ERK1/2 phosphorylation by administering MEK inhibitor, U0126, into Prdx6−/− mice before the probe test, which reversed their spatial memory deficit. This study is the first one to report the role of PRDX6 in spatial memory and synaptic plasticity. Our results revealed that PRDX6 is necessary for maintaining spatial memory by modulating ERK1/2 phosphorylation and astrocyte activation.

Graphic Abstract
Intraperitoneal injection of lithium chloride induces lateralized activation of the insular cortex in adult mice
Authors: Qian Kai , Liu Jiaqi , Cao Yiqing , Yang Jing , Qiu Shuang 
Published: April 2021

AbstractInsular cortex is a critical brain region that participates in the interoceptive sensations. Here, we combined the iDISCO + method and Fos immunostaining to confirm that the middle part of the right-side, but not the left-side, insular cortex in adult male mice is activated by intraperitoneal injection of lithium chloride. Lateralized activation of the insular cortex is also observed in adult female mice, but not in young or aged male mice. Furthermore, asymmetrical activation of the insular cortex was completely blocked when both sides of the vagal nerve are transected, whereas intravenous injection of lithium chloride has no effect on the insular activation. Combined together, these results indicate that the insular cortex unilaterally responds to aversive visceral stimuli in an age-dependent way and this process depends on the vagal afferent pathways.