bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teleophthalmology-enabled and artificial intelligence-ready referral pathway for community optometry referrals of retinal disease (HERMES): a Cluster Randomised Superiority Trial with a linked Diagnostic Accuracy Study—HERMES study report 1—study protocol
Authors: Han Ji Eun Diana , Liu Xiaoxuan , Bunce Catey , Douiri Abdel , Vale Luke , Blandford Ann , Lawrenson John , Hussain Rima , Grimaldi Gabriela , Learoyd Annastazia E , Kernohan Ashleigh , Dinah Christiana , Minos Evangelos , Sim Dawn , Aslam Tariq , Patel Praveen J , Denniston Alastair K , Keane Pearse A , Balaskas Konstantinos 
Published: February 2022

IntroductionRecent years have witnessed an upsurge of demand in eye care services in the UK. With a large proportion of patients referred to Hospital Eye Services (HES) for diagnostics and disease management, the referral process results in unnecessary referrals from erroneous diagnoses and delays in access to appropriate treatment. A potential solution is a teleophthalmology digital referral pathway linking community optometry and HES.Methods and analysisThe HERMES study (Teleophthalmology-enabled and artificial intelligence-ready referral pathway for community optometry referrals of retinal disease: a cluster randomised superiority trial with a linked diagnostic accuracy study) is a cluster randomised clinical trial for evaluating the effectiveness of a teleophthalmology referral pathway between community optometry and HES for retinal diseases. Nested within HERMES is a diagnostic accuracy study, which assesses the accuracy of an artificial intelligence (AI) decision support system (DSS) for automated diagnosis and referral recommendation. A postimplementation, observational substudy, a within-trial economic evaluation and discrete choice experiment will assess the feasibility of implementation of both digital technologies within a real-life setting. Patients with a suspicion of retinal disease, undergoing eye examination and optical coherence tomography (OCT) scans, will be recruited across 24 optometry practices in the UK. Optometry practices will be randomised to standard care or teleophthalmology. The primary outcome is the proportion of false-positive referrals (unnecessary HES visits) in the current referral pathway compared with the teleophthalmology referral pathway. OCT scans will be interpreted by the AI DSS, which provides a diagnosis and referral decision and the primary outcome for the AI diagnostic study is diagnostic accuracy of the referral decision made by the Moorfields-DeepMind AI system. Secondary outcomes relate to inappropriate referral rate, cost-effectiveness analyses and human–computer interaction (HCI) analyses.Ethics and disseminationEthical approval was obtained from the London—Bromley Research Ethics Committee (REC 20/LO/1299). Findings will be reported through academic journals in ophthalmology, health services research and HCI.Trial registration numberISRCTN18106677(protocol V.1.1).
Loneliness and mental well-being in the Polish population during the COVID-19 pandemic: a cross-sectional study
Authors: Kobos Ewa , Knoff Barbara , Dziedzic Beata , Maciąg Rafał , Idzik Anna 
Published: February 2022

ObjectiveThere is a growing concern that the restrictions imposed due to the COVID-19 pandemic could lead to increased loneliness and mental disorders, which are considered a major public health problem. The aim of the study was to assess loneliness, anxiety, depression and irritability in the Polish population during the COVID-19 pandemic.DesignA cross-sectional study. The study participants completed an online questionnaire using the computer-assisted web interview technique. Data were collected using Revised UCLA Loneliness Scale and Hospital Anxiety and Depression Scale.SettingPoland.ParticipantsThis study was conducted between 6 October and 12 October 2020, in a representative sample of 890 Polish residents.Primary outcome measuresSelf-reported loneliness; sociodemographic and COVID-19 pandemic factors associated with loneliness, anxiety, depression and irritability.ResultsThe analyses showed a moderately high degree of loneliness in 22%, symptoms of anxiety in 27%, depression in 14% and irritability in 33% of the respondents. The increasing severity of anxiety, depression and irritation in the study group was accompanied by higher loneliness. Generally, younger people, both tested positive for SARS-CoV-2 and those who experienced home quarantine, scored higher in both scales.ConclusionsIt is necessary to identify those most vulnerable to loneliness, anxiety and depression during a crisis to assess health needs and proactively allocate resources during and after the pandemic. Loneliness, anxiety, depression and irritability are important factors to consider in a population of younger, disadvantaged people, who tested positive for SARS-CoV-2, people who were quarantined at home, and people who believe that their physical and mental health is worse than in the pre-pandemic period. It is important to cater for the mental health of individuals during the COVID-19 pandemic and to promote psychological interventions to improve mental well-being in potentially vulnerable social groups.
Health-related quality of life of patients with haemophilia: a cross-sectional survey in the Northeast of China
Authors: Niu Jinyu , Ning Liangwen , Zhang Qiao , Liu Ze , Ma Yi , Xu Xiaoxue , Wu Qunhong , Hao Yanhua , Cui Yu , Liu Chaojie 
Published: February 2022

IntroductionHaemophilia is a hereditary, chronic and haemorrhagic disorder caused by a deficiency in coagulation factors. Long-term spontaneous bleeding of joints and soft tissues can seriously affect the quality of life of patients.ObjectiveThe study aimed to assess the health-related quality of life (HRQoL) of patients with haemophilia and associated factors.MethodsA snowball sampling strategy was adopted to select study participants. Eligible participants were those who were 18 years or older and had mild, moderate or severe haemophilia. They were asked to self-complete a questionnaire, collecting data regarding their sociodemographic characteristics, target joint status and HRQoL measured by the EQ-5D-5L(a tool developed by the European quality of life (EuroQol) Group).ResultsThe respondents reported a mean EQ-5Dutility(country-specific valuesets for the EQ-5D-5L) score of 0.51 (SD=0.34). Those with severe haemophilia had a lower utility score than those with mild/moderate haemophilia (0.46±0.37 vs 0.56±0.30, p=0.737). The linear regression analyses showed that older age (>25 years), two or more target joints, not working, low levels of knowledge of the disease and borrowing money to pay for medical treatments were associated with lower EQ-5Dutility scores.ConclusionLow HRQoL of patients with haemophilia is evident in China. Social support needs to be strengthened to address this issue.
Barriers and facilitators perceived by healthcare professionals for implementing lifestyle interventions in patients with osteoarthritis: a scoping review
Authors: Bouma Sjoukje E , van Beek Juliette F E , Diercks Ron L , van der Woude Lucas H V , Stevens Martin , van den Akker-Scheek Inge 
Published: February 2022

ObjectiveTo provide an overview of barriers and facilitators that healthcare professionals (HCPs) perceive regarding the implementation of lifestyle interventions (LIs) in patients with hip and/or knee osteoarthritis (OA).DesignScoping review.Data sourcesThe databases PubMed, Embase, CINAHL, PsycINFO and the Cochrane Library were searched from inception up to January 2021.Eligibility criteriaPrimary research articles with a quantitative, qualitative or mixed-methods design were eligible for inclusion if they reported: (1) perceptions of primary and/or secondary HCPs (population); (2) on implementing LIs with physical activity and/or weight management as key components (concept) and (3) on conservative management of hip and/or knee OA (context). Articles not published in English, German or Dutch were excluded.Data extraction and synthesisBarriers and facilitators were extracted by two researchers independently. Subsequently, the extracted factors were linked to a framework based on the Tailored Implementation for Chronic Diseases checklist.ResultsThirty-six articles were included. In total, 809 factors were extracted and subdivided into nine domains. The extracted barriers were mostly related to non-optimal interdisciplinary collaboration, patients’ negative attitude towards LIs, patients’ low health literacy and HCPs’ lack of knowledge and skills around LIs or promoting behavioural change. The extracted facilitators were mostly related to good interdisciplinary collaboration, a positive perception of HCPs’ own role in implementing LIs, the content or structure of LIs and HCPs’ positive attitude towards LIs.ConclusionsMultiple individual and environmental factors influence the implementation of LIs by HCPs in patients with hip and/or knee OA. The resulting overview of barriers and facilitators can guide future research on the implementation of LIs within OA care. To investigate whether factor frequency is related to the relevance of each domain, further research should assess the relative importance of the identified factors involving all relevant disciplines of primary and secondary HCPs.PROSPERO registration numberCRD42019129348.
Changes in cardiovascular mortality in Chile during the COVID-19 pandemic
Authors: Chang Sheng-Wei , Zitko Pedro , Passi-Solar Álvaro , Danaei Goodarz , Margozzini Paula 
Published: February 2022

ObjectivesThe COVID-19 pandemic has impacted regular cardiovascular healthcare access and delivery. Service utilisation has declined, and excess cardiovascular mortality has been reported in several countries. We aim to estimate excess cardiovascular deaths in Chile during 2020.MethodsWe collected mortality data from the Chilean Department of Statistics and Health Information and refined them using the maps of Global Burden of Disease Studies in 2017 and 2010. We conducted a time series analysis using quasi-Poisson distribution to predict cardiovascular mortality in 2020 and compared it with observed numbers and calculated attributable fractions (AFs) with 95% uncertainty intervals, as a whole and by sex, age group and type of cardiovascular disease.ResultsDuring 2015–2020, 173 283 cardiovascular deaths were recorded, with 28 141 deaths in 2020. The observation in 2020 was lower than our projection in the overall data (−4.0% (−5.0% to −2.8%)) and in male (−11.7% (−13% to −10.3%)). However, positive AFs were noted among female (5.0% (3.2% to 6.8%)), people in age group 80–89 years (11.0% (8.6% to 13.5%)) and people who died from hypertensive heart diseases (18.9% (14.7% to 23.5%)).ConclusionsLess overall cardiovascular deaths were observed in 2020 compared with our projection, possibly associated with competing risks from COVID-19 infection in men. Nonetheless, excess cardiovascular deaths were observed among women, people in the age group 80–89 years and people who died from hypertensive heart diseases suggesting possible negative cardiovascular impacts brought by the pandemic on these vulnerable groups.
Phase II study of atezolizumab with bevacizumab for non-squamous non-small cell lung cancer with high PD-L1 expression (@Be Study)
Authors: Seto Takashi , Nosaki Kaname , Shimokawa Mototsugu , Toyozawa Ryo , Sugawara Shunichi , Hayashi Hidetoshi , Murakami Haruyasu , Kato Terufumi , Niho Seiji , Saka Hideo , Oki Masahide , Yoshioka Hiroshige , Okamoto Isamu , Daga Haruko , Azuma Koichi , Tanaka Hiroshi , Nishino Kazumi , Tohnai Rie , Yamamoto Nobuyuki , Nakagawa Kazuhiko 
Published: February 2022

BackgroundPD-L1 expression on tumor cells is a marker of PD-1/PD-L1 antibody treatment efficacy for advanced non-small cell lung cancer (NSCLC). PD-L1 antibody (atezolizumab) prolongs overall survival (OS) compared with platinum doublet as first-line treatment for NSCLC with high PD-L1 expression. Bevacizumab enhanced cytotoxic agent and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor efficacy in non-squamous (NS)-NSCLC, and PD-1/PD-L1 antibodies in preclinical models.MethodsThis single-arm phase II study investigated clinical benefits of adding bevacizumab 15 mg/kg to atezolizumab 1200 mg fixed dose in a first-line setting for advanced NS-NSCLC patients with PD-L1 expression ≥50% without EGFR/ALK/ROS1 alterations. Primary endpoint was objective response rate (ORR) assessed by central review committee. Secondary endpoints were progression-free survival (PFS), duration of response (DOR), OS, and safety.ResultsOf 39 enrolled patients, 33 (84.6%) had stage IV NSCLC and 36 (92.3%) had smoking history. As of March 31, 2020, no patient had a complete response and 25 patients had a partial response (ORR=64.1%, 95% CI 47.18 to 78.80). Twelve-month PFS and OS rates were 54.9% (35.65 to 70.60) and 70.6% (50.53 to 83.74), respectively. The median DOR in 25 responders was 10.4 months (4.63–not reached). The median treatment cycle was 12 (1 to 27). Nineteen patients discontinued study treatment because of disease progression (N=17) or immune-related adverse events (AEs) (N=2) (sclerosing cholangitis or encephalopathy). There were 23 serious AEs in 12 patients, but no grade 4/5 toxicity.ConclusionsAtezolizumab with bevacizumab is a potential treatment for NS-NSCLC with high PD-L1 expression.Trial registration numberJapicCTI-184038.
Human leucocyte antigens profiling in Malay female patients with systemic lupus erythematosus: are we the same or different?
Authors: Selvaraja Malarvili , Too Chun Lai , Tan Lay Kim , Koay Bee Tee , Abdullah Maha , Shah Anim Md , Arip Masita , Amin-Nordin Syafinaz 
Published: February 2022

ObjectiveSLE is a heterogeneous autoimmune disease, in terms of clinical presentation, incidence and severity across diverse ethnic populations. We investigated the human leucocyte antigens (HLA) profile (ie, HLA-A, HLA-B and HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1 and HLA-DPB1) in Malaysian Malay female patients with SLE and determined the generalisability of the published HLA risk factors across different ethnic populations globally including Malaysia.MethodsOne hundred Malay female patients with SLE were recruited between January 2016 and October 2017 from a nephrology clinic. All patients were genotyped for HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1 and HLA-DPB1 alleles using PCR sequence-specific oligonucleotides method on Luminex platform. A total of 951 HLA genotyped population-based Malay control subjects was used for association testing by means of OR with 95% CIs.ResultsOur findings convincingly validated common associations between HLA−A*11 (OR=1.65, p=3.36×10−3, corrected P (Pc)=4.03×10−2) and DQB1*05:01 (OR=1.56, p=2.02×10−2, Pc=non−significant) and SLE susceptibility in the Malay population. In contrast, DQB1*03:01 (OR=0.51, p=4.06×10−4, Pc=6.50×10−3) were associated with decreased risk of SLE in Malay population. Additionally, we also detected novel associations of susceptibility HLA genes (ie, HLA-B*38:02, DPA1*02:02, DPB1*14:01) and protective HLA genes (ie, DPA1*01:03). When comparing the current data with data from previously published studies from Caucasian, African and Asian populations, DRB1*15 alleles, DQB1*03:01 and DQA1*01:02 were corroborated as universal susceptibility and protective genes.ConclusionsThis study reveals multiple HLA alleles associated with susceptibility and protection against risk of developing SLE in Malay female population with renal disorders. In addition, the published data from different ethnic populations together with our study further support the notion that the genetic effects from association with DRB1*15:01/02, DQB1*03:01 and DQA1*01:02 alleles are generalised to multiple ethnic populations of Caucasian, African and Asian descents.
Prognostic Value of Histidine-Rich Glycoprotein for Community-Acquired Pneumonia
Authors: He Xinwei , Luo Qiongzhen , Zhao Lili , Shang Ying , Gao Zhancheng 
Published: February 2022

Purpose. Histidine-rich glycoprotein (HRG) is abundant in serum and has been implicated in several processes including blood coagulation and immune response. This prospective study is aimed at exploring HRG as a biomarker in patients hospitalized for community-acquired pneumonia (CAP). Methods. A total of 160 patients (73 severe CAP, 57 nonsevere CAP), and 30 healthy controls were enrolled in 2019. Demographic and clinical data were recorded for all patients. Serum HRG concentration was measured upon admission using ELISA. Results. HRG levels were significantly lower in severe CAP patients compared with other groups, regardless of etiology, and were negatively correlated with serum interleukin-6 and disease severity index scores. Combination of CURB-65, PSI, and APACHE II scores with HRG values significantly improved the accuracy of predicting 30-day mortality in these patients. Cox regression analysis showed that HRG could serve as an independent risk factor for 30-day mortality. Notably, patients with

HRG
≤
16.92

μ
g
/
mL

had significantly lower cumulative survival than those with

HRG
>
16.92

μ
g
/
mL

. Conclusion. Serum HRG levels are lower in patients with severe CAP and are negatively correlated with disease severity scores. Measurement of HRG upon admission can provide valuable prognostic information for patients with CAP.
Disruption of Prostaglandin E2 Signaling in Cancer-Associated Fibroblasts Limits Mammary Carcinoma Growth but Promotes Metastasis
Authors: Elwakeel Eiman , Brüggemann Mirko , Wagih Jessica , Lityagina Olga , Elewa Mohammed A.F. , Han Yingying , Frömel Timo , Popp Rüdiger , Nicolas Adele M. , Schreiber Yannick , Gradhand Elise , Thomas Dominique , Nüsing Rolf , Steinmetz-Späh Julia , Savai Rajkumar , Fokas Emmanouil , Fleming Ingrid , Greten Florian R. , Zarnack Kathi , Brüne Bernhard , Weigert Andreas 
Published: February 2022

Abstract

The activation and differentiation of cancer-associated fibroblasts (CAF) are involved in tumor progression. Here, we show that the tumor-promoting lipid mediator prostaglandin E2 (PGE2) plays a paradoxical role in CAF activation and tumor progression. Restricting PGE2 signaling via knockout of microsomal prostaglandin E synthase-1 (mPGES-1) in PyMT mice or of the prostanoid E receptor 3 (EP3) in CAFs stunted mammary carcinoma growth associated with strong CAF proliferation. CAF proliferation upon EP3 inhibition required p38 MAPK signaling. Mechanistically, TGFβ–activated kinase-like protein (TAK1L), which was identified as a negative regulator of p38 MAPK activation, was decreased following ablation of mPGES-1 or EP3. In contrast with its effects on primary tumor growth, disruption of PGE2 signaling in CAFs induced epithelial-to-mesenchymal transition in cancer organoids and promoted metastasis in mice. Moreover, TAK1L expression in CAFs was associated with decreased CAF activation, reduced metastasis, and prolonged survival in human breast cancer. These data characterize a new pathway of regulating inflammatory CAF activation, which affects breast cancer progression.

Significance:
The inflammatory lipid prostaglandin E2 suppresses cancer-associated fibroblast expansion and activation to limit primary mammary tumor growth while promoting metastasis.
Aterro da Baía Sul, em Florianópolis: interpretação de um patrimônio moderno
Authors: Ferraro Luiza Helena , Yunes Gilberto Sarkis 
Published: February 2022

O objetivo desse artigo é discutir o aterro da Baía Sul, em Florianópolis,Santa Catarina, reconhecendo os valores desse território como patrimônio moderno da cidade. A revisão bibliográfica e documental acerca do objeto em estudo e do patrimônio urbano foi o método de pesquisa utilizado. O trabalho apresentado é parte da pesquisa de mestrado da autora e consistena análise sobre as potencialidades desse significativo espaço da cidade. Para isso, faz-se a interpretação dos dados obtidos, como o decreto de tombamento da área estudada, relacionando-os às leituras sobre o patrimônio urbano dos autores Hugues de Varine (2013), o qual trabalha com o patrimônio como desenvolvimento, e Márcia Sant`Anna (2015), que entende a cidade como documento e registro dos tempos, e desta maneira, discute-se esse espaço da cidade a partir de uma perspectiva patrimonial. A identificação desses autores e as relações que se faz dessas categorias de pensamento com o espaço analisado direciona uma nova forma de interpretar o aterro, refletindo sobre atributos que definam valores patrimoniais afetivos, funcionais, culturais, financeiros, comunitário e potencial. Assim, obtêm-se reflexões para se considerar em futuras pesquisas e intervenções no aterro da Baía Sul.
Complexo pavilhonar da Santa Casa de Misericórdia do Pará: cronologia e percepção de valores
Authors: Miranda Cybelle Salvador , Lobato Beatriz Trindade de Oliveira 
Published: February 2022

A Santa Casa de Misericórdia do Pará é um exemplar da tipologia pavilhonar difundida pelos países europeus, durante o período do urbanismo sanitarista. O estudo do processo de construção deste modelo é essencial para a compreensão da história da saúde, em especial a sua aplicação em Belém. Este trabalho visa entender a anatomia deste complexo arquitetônico e seu crescimento ao longo das décadas, até alcançar a extensão e importância atual. Pretende-se discutir também sob a perspectiva de patrimônio cultural da saúde, sob os aspectos de uma instituição que funcionou como local de aprendizado para profissionais da saúde, desenvolvimento de pesquisas e vacinas, além do seu papel como hospital dedicado a assistência. Aborda-se também sua arquitetura, e os elementos que a compõem, e quais as modificações que foram e ainda são realizadas no conjunto. Além desses aspectos, objetiva-se compreender a partir do valor memorial e afetivo atribuído por seus usuários, aqueles que convivem e conviveram no hospital.
Transvenous Approaches to the Vertebral‐Venous Plexus for Endovascular Treatment of Cervical Epidural Arteriovenous Fistulas: Anatomy and Technique
Authors: Caton Michael T. , Isikbay Masis , Narsinh Kazim H. , Baker Amanda , Milburn James , Cooke Daniel L. , Hetts Steven W. , Dowd Christopher F. , Higashida Randall T. , Amans Matthew R. 
Published: February 2022

Background
Spinal epidural arteriovenous fistulas (seAVF) are a rare subset of vascular lesions that are most commonly found in the cervical levels. Unlike spinal dural AVF, seAVF are typically supplied by multiple arteries, including direct branches from the vertebral artery, which increases the risk of nontarget embolization using a transarterial endovascular approach. In these cases, transvenous embolization may be a preferable option, but accessing the cervical epidural venous space, also termed the internal vertebral venous plexus, can be challenging and requires advanced foreknowledge of cervical venous channels.

Methods
The authors review salient neurovascular anatomy and present 2 techniques for endovascular access of the cervical epidural space to treat seAVF.

Results
The physiology and structure of the cervical internal vertebral venous plexus is briefly reviewed. Next, the authors describe 2 complementary methods for transvenous access to the cervical internal vertebral venous plexus via the jugular vein (cranial‐caudal) and the vertebral vein (caudal‐cranial). The first approach involves retrograde microcatheterization via the jugular bulb and condylar veins. The second approach involves direct antegrade approach via the vertebral vein, arising from the brachiocephalic vein. Both approaches enable stable catheter positioning for coil embolization at remote cervical levels to treat a wide spectrum of seAVF.

Conclusions
Accessing the cervical epidural venous space is technically demanding and requires effective planning and knowledge of relevant spinal venous anatomy. These techniques are important tools for safe and effective endovascular treatment of seAVF.