bluuebunny/crossref_metadata_2025_split huggingface dataset:
“We Are at Risk Too”: The Disparate Mental Health Impacts of the Pandemic on Younger Generations: Nous Sommes Aussi à Risque: Les Effets Disparates de la Pandémie Sur la Santé Mentale des Générations Plus Jeunes
Authors: El-Gabalawy Renée , Sommer Jordana L. 
Published: February 2021

Objectives: The coronavirus 2019 (COVID-19) pandemic has resulted in profound global impact, with older adults at greater risk of serious physical health outcomes. It is essential to also understand generational differences in psychosocial impacts to identify appropriate prevention and intervention targets. Across generational groups, this study examined: (1) rates of precautions and adaptive and maladaptive health behaviors, (2) differences in levels of anxiety, and (3) rates of COVID-related concerns during Wave 1 of COVID-19 in Canada. Participants: We analyzed data from 2 Canadian population-based data sets: the Canadian Perspective Survey Series: Impact of COVID-19 survey ( N = 4,627; March 29 to April 3, 2020), and Crowdsourcing: Impacts of COVID-19 on Canadians—Your Mental Health ( N = 45,989; April 24 to May 11, 2020). Measures: We categorized generational age group. Participants self-reported changes in behaviors and COVID-related concerns, and a validated measure assessed anxiety symptoms. Results: There are generational differences in behavioral responses to the pandemic. Adaptive health habits (e.g., exercise) were comparable across groups, while changes in maladaptive health habits (e.g., substance use) were highest among younger age groups, particularly Millennials (15 to 34 years old). COVID-related precautions were also highest among the younger generations, with Generation X (35 to 54 years old) exhibiting the highest rate of precautionary behavior. Results also revealed that the highest rate of clinically significant anxiety is among Millennials (36.0%; severe anxiety = 15.7%), and the younger generations have the highest rates of COVID-related concerns. Conclusion: These early data are essential in understanding at-risk groups given the unpredictable nature of the pandemic and its potential long-term implications.
Alendronate promotes the gene expression of extracellular matrix mediated by SP-1/SOX-9
Authors: Wang L , Mi B , Zhang Y , Yan H , Zhu H 
Published: February 2021

Background and purpose: Osteoarthritis (OA) is a disease with significant degenerative changes of articular cartilage, which is reported to be closely related to the integrity of chondrocytes extracellular matrix (ECM). Alendronate belongs to the family of bisphosphonates with promising cartilage repair function. In the present study, the effects of Alendronate on the gene expression of chondrocytes ECM and the potential mechanism will be investigated to explore the potential therapeutic property of Alendronate on OA. Methods: Human SW1353 chondrocytes were stimulated with 1 and 2 μM Alendronate for 12 h. The gene expression of Col2α1, COL9α2, and Acan in the treated chondrocytes was determined by qRT-PCR. QRT-PCR and western blot analysis were used to evaluate the expression level of SOX-9 in the treated chondrocytes. The expression level of SP-1 was checked by qRT-PCR and immunostaining. SiRNA against SP-1 was transfected into chondrocytes to knockdown the expression of SP-1. The levels of p-ERK1/2 and total ERK1/2 were examined using western blot analysis. TNF-α was used to induce an OA-like in vitro model in the chondrocytes for therapeutic evaluations. Results: Treatment with Alendronate increased the levels of ECM related genes ( Col2α1, COL9α2, and Acan) in a dose-dependent manner through increasing the expression of SOX-9, a central regulator of ECM genes. Additionally, our findings demonstrate that the effects of Alendronate in the expression of SOX-9 are mediated by SP-1 as silencing of SP-1 abolished these effects. Notably, Alendronate increased the phosphorylation of ERK1/2 and inhibition of ERK1/2 using its specific inhibitor U0126 blocked the expression of SP-1. Finally, we found that treatment with Alendronate could rescue TNF-α-induced reduction of Col2α1, COL9α2, Acan and SOX-9. Conclusion: Our data indicated that Alendronate might promote the gene expression of extracellular matrix through SOX-9 mediated by the ERK1/2/SP1 signaling pathway.
Supporting diversity in person-centred care: The role of healthcare chaplains
Authors: Brady Vivienne , Timmins Fiona , Caldeira Sílvia , Naughton Margaret Theresa , McCarthy Anne , Pesut Barbara 
Published: February 2021

Aim: To explore healthcare chaplains’ experience of providing spiritual support to individuals and families from minority religious and non-religious faiths and to identify key elements of the role. Background: Currently, there is limited research uncovering the essential elements of healthcare chaplaincy, specifically with reference to religious and/or spiritual diversity, and as interprofessional collaborators with nurses and midwives in healthcare. Research design and participants: Using phenomenology, we interviewed eight healthcare chaplains from a variety of healthcare settings in the Republic of Ireland. Data were analysed using a seven-step framework comprising Moustakas’ (1994) modification of the Van Kaam method of data analysis. Ethical considerations: Ethical approval was granted by the university and the principles of informed consent applied. Findings: Three main themes emerged: what the chaplain brings; components of ritual, minority faith or no faith; and practising chaplaincy. Subthemes included ‘offering’, ‘awareness and insight’, ‘acceptance and empathy’, ‘skilled companionship’, ‘presence’, ‘a confidant and holder of hope’ and ‘a vital resource’. Discussion and conclusions: The healthcare chaplain is a key collaborator in facilitating holistic person-centred care and in supporting healthcare professionals. Chaplaincy services are an essential but largely unrecognised and potentially cost-effective component of interprofessional team working. Relevance to clinical practice: This study has illuminated key aspects of the healthcare chaplain’s role as interprofessional collaborator in person-centred care, in navigating diversity and ensuring respect and dignity for the person irrespective of religious or spiritual care needs.
Surgical Variation Between Consultant Surgeons Performing a Sommerlad Radical Intravelar Veloplasty
Authors: Butterworth Sophie , Hodgkinson Emma L. , Sainsbury David C.G. , Hodgkinson Peter D. 
Published: February 2021

Background: Although cleft surgeons in the United Kingdom follow a similar training pathway, and cleft centers adhere to similar protocols regarding timing of palate surgery and surgical technique, speech outcomes still vary significantly between centers. Objective: To explore if differences in technique exist between individual surgeons, performing a Sommerlad radical intravelar veloplasty (IVVP). Design: An exploratory, qualitative approach was adopted to understand the views of UK cleft surgeons performing a Sommerlad radical IVVP for primary cleft palate repair and to discuss what was important in the adoption, adaptation, and evolution of this technique within their own practice. Method: A semistructured interview schedule was designed. Interviews were conducted in person or via videoconferencing, with interested surgeons. The interviews were recorded, transcribed, and checked for accuracy. Analysis involved inductive thematic analysis. Results: Fourteen cleft consultants from the United Kingdom participated (3 females and 11 males). Seven of the consultants were trained in plastic surgery and 4 in oral and maxillofacial surgery. Eight themes were identified from the thematic analysis. One theme—Surgical Variation—is discussed. Conclusions: The findings provide insight into areas of variation seen within one surgical technique of cleft palate repair. These variations may have arisen to accommodate heterogeneity in the patient population or may have evolved in relation to different experiences of training or influences of colleagues. Further work is needed to explore the reasons for these differences in technique and to identify if any of these subtle differences contributed to variability in outcomes.
Repeated Dose Toxicity Study and Developmental and Reproductive Toxicology Studies of a Respiratory Syncytial Virus Candidate Vaccine in Rabbits and Rats
Authors: Stokes Alan H. , Franklin Kelle , Fisher Daniel E. , Posobiec Lorraine M. , Binazon Ornella , Tripathi Niraj , Ringenberg Michael Alan , Charlap Jeffrey , Ziejewski Mary K. , Vemireddi Vimala , Khanna Weiss Payal , Majumdar Ritankar , Bouzya Badiaa , Donner Marie-Noëlle , Rodriguez Luis-Alexander , Baumeister Judith 
Published: February 2021

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections, and vaccines are needed to treat young children and older adults. One of GSK’s candidate vaccines for RSV contains recombinant RSVPreF3 protein maintained in the prefusion conformation. The differences in immune function of young children and older adults potentially require different vaccine approaches. For young children, anti-RSV immunity can be afforded during the first months of life by vaccinating the pregnant mother during the third trimester with unadjuvanted RSVPreF3, which results in protection of the infant due to the transplacental passage of anti-RSV maternal antibodies. For older adults with a waning immune response, the approach is to adjuvant the RSVPreF3 vaccine with AS01 to elicit a more robust immune response. The local and systemic effects of biweekly intramuscular injections of the RSVPreF3 vaccine (unadjuvanted, adjuvanted with AS01, or coadministered with a diphtheria-tetanus-acellular pertussis vaccine) was tested in a repeated dose toxicity study in rabbits. After three intramuscular doses, the only changes observed were those commonly related to a vaccine-elicited inflammatory reaction. Subsequently, the effects of unadjuvanted RSVPreF3 vaccine on female fertility, embryo-fetal, and postnatal development of offspring were evaluated in rats and rabbits. There were no effects on pregnancy, delivery, lactation, or the pre- and postnatal development of offspring. In conclusion, the RSVPreF3 vaccine was well-tolerated locally and systemically and was not associated with any adverse effects on female reproductive function or on the pre- and postnatal growth and development of offspring.
Comparison of posterior capsule opacification between Clareon CNA0T0 and Tecnis ZCB00 intraocular lenses
Authors: Almenara Cristina , Bartol-Puyal Francisco de Asís , Soriano Diana , Idoipe Miriam , Chacón María , Méndez-Martínez Silvia , Giménez Galadriel , Polo Vicente 
Published: February 2021

Introduction: The purpose is to compare posterior capsule opacification (PCO) and its impact on vision between Clareon CNA0T0 (Alcon) and Tecnis ZCB00 intraocular lenses (IOLs) (Johnson&Johnson) 1, 6, and 12 months after implantation. Methods: A prospective observational study was performed at the Nuestra Señora de Gracia Hospital (Zaragoza, Spain). Fifty eyes (50 patients) with Tecnis IOL (group 1) and 60 eyes (60 patients) with Clareon IOL (group 2) were enrolled. One, 6, and 12 months after age-related cataract surgery by five different surgeons, the following tests were performed: mesopic corrected distance visual acuity (CDVA), CSV1000-E test, KR-1W wavefront analyzer, OQAS II, Catquest-9SF questionnaire and mydriatic slit-lamp pictures. PCO intensity was quantified and the area of opacification was measured using ImageJ (NIH). Results: Mean age was 71.20 ± 6.79 years in group 1, and 71.73 ± 8.17 years in group 2 ( p = 0.72); mean axial length was 23.46 ± 1.14 and 23.53 ± 0.91 mm, respectively ( p = 0.72); mean IOL power was 21.69 ± 2.26 D and 21.28 ± 2.44 D, respectively ( p = 0.37). One month after surgery there were differences in intensity of PCO (0.73 ± 0.60 and 1.05 ± 0.71, respectively, p = 0.02). Six months after surgery statistical differences were found in VA with 20% CS in mydriatic conditions (0.26 ± 0.21 logMAR (20/36) and 0.18 ± 0.17 logMAR (20/30), respectively, p = 0.04). Twelve months after surgery, no differences were detected between groups. As for the evolution of PCO within the Clareon group, high order aberrations ( p < 0.05) and the Strehl ratio ( p = 0.02) decreased. Conclusion: There are no differences in slit-lamp pictures or visual function between both IOLs during the first 12 months after implantation.
Hypobaria-Induced Oxidative Stress Facilitates Homocysteine Transsulfuration and Promotes Glutathione Oxidation in Rats with Mild Traumatic Brain Injury
Authors: Tchantchou Flaubert , Miller Catriona , Goodfellow Molly , Puche Adam , Fiskum Gary 
Published: February 2021

Background: United States service members injured in combat theatre are often aeromedically evacuated within a few days to regional military hospitals. Animal and epidemiological research indicates that early exposure to flight hypobaria may worsen brain and other injuries. The mechanisms by which secondary exposure to hypobaria worsen trauma outcomes are not well elucidated. This study tested the hypothesis that hypobaria-induced oxidative stress and associated changes in homocysteine levels play a role in traumatic brain injury (TBI) pathological progression caused by hypobaria. Methods: Male Sprague Dawley rats were exposed to a 6 h hypobaria 24 h after mild TBI by the controlled cortical impact. Plasma and brain tissues were assessed for homocysteine levels, oxidative stress markers or glutathione metabolism, and behavioral deficits post-injury in the absence and presence of hypobaria exposure. Results: We found that hypobaria after TBI increased oxidative stress markers, altered homocysteine metabolism, and promoted glutathione oxidation. Increased glutathione metabolism was driven by differential upregulation of glutathione metabolizing genes. These changes correlated with increased anxiety-like behavior. Conclusion: These data provide evidence that hypobaria exposure after TBI increases oxidative stress and alters homocysteine elimination likely through enhanced glutathione metabolism. This pathway may represent a compensatory mechanism to attenuate free radical formation. Thus, hypobaria-induced enhancement of glutathione metabolism represents a potential therapeutic target for TBI management.
Successful treatment of chronic type B aortic dissection complicated by disseminated intravascular coagulopathy with recombinant human soluble thrombomodulin after thoracic endovascular aortic repair
Authors: Iida Yasunori , Asano Ryota , Hachiya Takashi 
Published: February 2021

Objectives We report a case of successful thoracic endovascular aortic repair (TEVAR) of chronic type B aortic dissection complicated by disseminated intravascular coagulopathy. Methods The patient suffered from chronic type B aortic dissection coexisting with a large false lumen and an intimal tear. He underwent TEVAR with left common carotid-left subclavian artery bypass. Results The following day, the patient exhibited a bleeding tendency and marked subcutaneous hemorrhage. He had a low fibrinogen level, a low platelet count, and high levels of fibrin dimer product and D-dimer. We diagnosed the condition as disseminated intravascular coagulopathy and administered recombinant human soluble thrombomodulin (rhTM). The patient recovered successfully from disseminated intravascular coagulopathy and was discharged on postoperative day 6. Conclusions We successfully treated a patient with chronic type B aortic dissection with a large intimal tear complicated by postoperative disseminated intravascular coagulopathy using TEVAR followed by rhTM administration. rhTM may be considered in patients with large intimal tear and false lumen.
Baseline lesion number as an efficacy predictive and independent prognostic factor and its joint utility with TMB for PD-1 inhibitor treatment in advanced gastric cancer
Authors: Wei Xiao-Li , Xu Jian-Ying , Wang De-Shen , Chen Dong-Liang , Ren Chao , Li Jia-Ning , Wang Feng , Wang Feng-Hua , Xu Rui-Hua 
Published: February 2021

Background: We previously reported tumor mutation burden (TMB) as a potential prognostic factor for patients with advanced gastric cancer (AGC) receiving immunotherapy. We aimed to comprehensively understand the impact of tumor burden and TMB on efficacy and prognosis in immunotherapy-treated AGC patients. Methods: A total of 58 patients with refractory AGC receiving PD-1 inhibitor monotherapy from a phase Ib/II clinical trial (ClinicalTrials.gov identifier: NCT02915432) were retrospectively included. Univariate and multivariate logistical regression analyses and the Cox proportional hazards model were performed for prognostic value of baseline factors. Factors reflecting baseline tumor burden, including baseline lesion number (BLN), the maximum tumor size (MTS) and the sum of target lesion size (SLS) were analyzed. The objective response rate (ORR) and disease control rate (DCR) were compared by Chi-square test. Results: In univariate analysis, high BLN was associated with poor median progression-free survival (mPFS) [1.7 months versus 3.4 months; hazard ratio (HR), 2.696, p < 0.05] and median overall survival (mOS) (3.2 months versus 7.6 months; HR, 1.997, p < 0.05), while high TMB was a positive prognostic factor. In multivariable analysis, both BLN and TMB were independent prognostic factors for mOS (BLN: HR, 2.782, p < 0.05; TMB: HR, 0.288, p < 0.05), while MTS or SLS had no association with survival. Better ORR and DCR were observed in the low BLN group (15.4% versus 5.3%, p > 0.05; 86.96% versus 54.29%, p < 0.05). When combining BLN and TMB, the best efficacy and survival were observed in the BLNlowTMBhigh group (ORR: 37.5%, DCR: 62.5%, mPFS and mOS: not reached). The worst efficacy and survival were shown in the BNLhighTMBlow group [ORR: 0% (0/15); DCR: 13.3%; mPFS: 1.7 months; mOS: 2.7 months (all p < 0.05)]. Conclusions: BLN, rather than factors regarding baseline tumor size, is perhaps a potential predictor for benefit from immunotherapy and its combination with TMB could further risk-stratify patients with AGC receiving immunotherapy.
Integrative Analysis of MicroRNA and mRNA Sequencing Data Identifies Novel Candidate Genes and Pathways for Developmental Dysplasia of Hip
Authors: Cheng Bolun , Jia Yumeng , Wen Yan , Hou Weikun , Xu Ke , Liang Chujun , Cheng Shiqiang , Liu Li , Chu Xiaomeng , Ye Jing , Yao Yao , Zhang Feng , Xu Peng 
Published: February 2021

Objective Our aim is to explore the candidate pathogenesis genes and pathways of developmental dysplasia of hip (DDH). Design Proliferating primary chondrocytes from hip cartilage were used for total RNA extraction including 5 DDH patients and 5 neck of femur fracture (NOF) subjects. Genome-wide mRNA and microRNA (miRNA) were then sequenced on the Illumina platform (HiSeq2500). Limma package was used for difference analysis of mRNA expression profiles. edgeR was used for difference analysis of miRNA expression profiles. miRanda was used to predict miRNA-target genes. The overlapped DDH associated genes identified by mRNA and miRNA integrative analysis were further compared with the differently expressed genes in hip osteoarthritis (OA) cartilage. Results Differential expression analysis identified 1,833 differently expressed mRNA and 186 differently expressed miRNA for DDH. Integrative analysis of mRNA and miRNA expression profiles identified 175 overlapped candidate genes (differentially expressed genes, DEGs) for DDH, such as VWA1, TMEM119, and SCUBE3. Further gene ontology enrichment analysis detected 111 candidate terms for DDH, such as skeletal system morphogenesis ( P = 4.92 × 10−5) and skeletal system development ( P = 8.85 × 10−5). Pathway enrichment analysis identified 14 candidate pathways for DDH, such as Hedgehog signaling pathway ( P = 4.29 × 10−5) and Wnt signaling pathway ( P = 4.42 × 10−2). Among the identified DDH associated candidate genes, we also found some genes were detected in hip OA including EFNA1 and VWA1. Conclusions We identified multiple novel candidate genes and pathways for DDH, providing novel clues for understanding the molecular mechanism of DDH.
Service-user efforts to maintain their wellbeing during and after successful withdrawal from antipsychotic medication
Authors: Larsen-Barr Miriam , Seymour Fred 
Published: February 2021

Background: It is well-known that attempting antipsychotic withdrawal can be a fraught process, with a high risk of relapse that often leads people to resume the medication. Nonetheless, there is a group of people who appear to be able to discontinue successfully. Relatively little is known about how people do this. Methods: A convenience sample of adults who had stopped taking antipsychotic medication for more than a year were recruited to participate in semi-structured interviews through an anonymous online survey that investigated antipsychotic medication experiences in New Zealand. Thematic analysis explored participant descriptions of their efforts to maintain their wellbeing during and after the withdrawal process. Results: Of the seven women who volunteered to participate, six reported bipolar disorder diagnoses and one reported diagnoses of obsessive compulsive disorder and depression. The women reported successfully discontinuing antipsychotics for 1.25–25 years; six followed a gradual withdrawal method and had support to prepare for and manage this. Participants defined wellbeing in terms of their ability to manage the impact of any difficulties faced rather than their ability to prevent them entirely, and saw this as something that evolved over time. They described managing the process and maintaining their wellbeing afterwards by ‘understanding myself and my needs’, ‘finding what works for me’ and ‘connecting with support’. Sub-themes expand on the way in which they did this. For example, ‘finding what works for me’ included using a tool-box of strategies to flexibly meet their needs, practicing acceptance, drawing on persistence and curiosity and creating positive life experiences. Conclusion: This is a small, qualitative study and results should be interpreted with caution. This sample shows it is possible for people who experience mania and psychosis to successfully discontinue antipsychotics and safely manage the impact of any symptoms that emerge as a result of the withdrawal process or other life stressors that arise afterwards. Findings suggest internal resources and systemic factors play a role in the outcomes observed among people who attempt to stop taking antipsychotics and a preoccupation with avoiding relapse may be counterproductive to these efforts. Professionals can play a valuable role in facilitating change.