bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of ERAD synergizes with FTS to eradicate pancreatic cancer cells
Authors: Du Rong , Sullivan Delaney K. , Azizian Nancy G. , Liu Yuanhui , Li Yulin 
Published: March 2021

AbstractBackgroundPancreatic ductal adenocarcinoma (PDAC), one of the most lethal cancers, is driven by oncogenic KRAS mutations. Farnesyl thiosalicylic acid (FTS), also known as salirasib, is a RAS inhibitor that selectively dislodges active RAS proteins from cell membrane, inhibiting downstream signaling. FTS has demonstrated limited therapeutic efficacy in PDAC patients despite being well tolerated.MethodsTo improve the efficacy of FTS in PDAC, we performed a genome-wide CRISPR synthetic lethality screen to identify genetic targets that synergize with FTS treatment. Among the top candidates, multiple genes in the endoplasmic reticulum-associated protein degradation (ERAD) pathway were identified. The role of ERAD inhibition in enhancing the therapeutic efficacy of FTS was further investigated in pancreatic cancer cells using pharmaceutical and genetic approaches.ResultsIn murine and human PDAC cells, FTS induced unfolded protein response (UPR), which was further augmented upon treatment with a chemical inhibitor of ERAD, Eeyarestatin I (EerI). Combined treatment with FTS and EerI significantly upregulated the expression of UPR marker genes and induced apoptosis in pancreatic cancer cells. Furthermore, CRISPR-based genetic ablation of the key ERAD components, HRD1 and SEL1L, sensitized PDAC cells to FTS treatment.ConclusionOur study reveals a critical role for ERAD in therapeutic response of FTS and points to the modulation of UPR as a novel approach to improve the efficacy of FTS in PDAC treatment.
First case of Phthirus pubis and Demodex co-infestation of the eyelids: a case report
Authors: Huo Yanan , Mo Yanping , Jin Xiuming , Huang Xiaodan , Chen Wei 
Published: March 2021

Abstract
Background
Phthirus pubis is an obligate parasite of human beings. Demodex spp. is a much more common parasite of human beings. However, P. pubis infestation accompanied by Demodex mite infestation in eye has not been reported.

Case presentation
We report the first case of Phthirus pubis and Demodex co-infestation on a 48-years-old woman. She presented to the hospital with itching and burning at her right eye for 2 weeks. Slit lamp examination revealed multiple nits and adults of P. pubis anchored to both upper and lower eyelashes. Eyelashes were trimmed, moxifloxacin eye ointment and fluorometholone eye drops were initiated daily. However, itching didn’t improve after 2 weeks of treatment. Light microscopy examination of eyelashes revealed infestation with Demodex. The patient was treated with lid scrubs with 25% tea tree oil daily for 4 weeks and was completely cured.

Conclusion
Our report shows the importance of an early and comprehensive diagnosis, because both phthiriasis palpebrarum and demodicosis can be confused with blepharitis.
BLEND-A: blending internet treatment into conventional face-to-face treatment for alcohol use disorder - a study protocol
Authors: Mellentin Angelina Isabella , Behrendt Silke , Bilberg Randi , Blankers Matthijs , Folker Marie Paldam , Tarp Kristine , Uffelmann Jakob , Nielsen Anette Søgaard 
Published: March 2021

Abstract
Background
A major challenge to psychological treatment for alcohol use disorder (AUD) is patient non-compliance. A promising new treatment approach that is hypothesized to increase patient compliance is blended treatment, consisting of face-to-face contact with a therapist combined with modules delivered over the internet within the same protocol. While this treatment concept has been developed and proven effective for a variety of mental disorders, it has not yet been examined for AUD.

Aims
The study described in this protocol aims to examine and evaluate patient compliance with blended AUD treatment as well as the clinical and cost effectiveness of such treatment compared to face-to-face treatment only.

Methods
The study design is a pragmatic, stepped-wedge cluster randomized controlled trial. The included outpatient institutions (planned number of patients: n = 1800) will be randomized in clusters to implement either blended AUD treatment or face-to-face treatment only, i.e. treatment as usual (TAU). Both treatment approaches consist of motivational interviewing and cognitive behavioral therapy. Data on sociodemographics, treatment (e.g. intensity, duration), type of treatment conclusion (compliance vs. dropout), alcohol consumption, addiction severity, consequences of drinking, and quality of life, will be collected at treatment entry, at treatment conclusion, and 6 months after treatment conclusion. The primary outcome is compliance at treatment conclusion, and the secondary outcomes include alcohol consumption and quality of life at six-months follow-up. Data will be analyzed with an Intention-to-treat approach by means of generalized linear mixed models with a random effect for cluster and fixed effect for each step. Also, analyses evaluating cost-effectiveness will be conducted.

Discussion
Blended treatment may increase treatment compliance and thus improve treatment outcomes due to increased flexibility of the treatment course. Since this study is conducted within an implementation framework it can easily be scaled up, and when successful, blended treatment has the potential to become an alternative offer in many outpatient clinics nationwide and internationally.

Trial registration
Clinicaltrials.gov.: NCT04535258, retrospectively registered 01.09.20.
Loneliness in early psychosis: a qualitative study exploring the views of mental health practitioners in early intervention services
Authors: Stefanidou Theodora , Wang Jingyi , Morant Nicola , Lloyd-Evans Brynmor , Johnson Sonia 
Published: March 2021

Abstract
Background
Loneliness is an important public health problem with established adverse effects on physical and mental health. Although people with psychosis often experience high levels of loneliness, relatively little is known about the relationship between loneliness and early psychosis. Potential interventions to address loneliness might be easier to implement early in the illness when social networks and social skills may be more intact than at a later stage. We investigated the views of mental health practitioners about the context and causes of loneliness in people with early psychosis, and about potential interventions.

Methods
Semi-structured face-to-face interviews were conducted with mental health practitioners (n = 20). Participants were purposively recruited from four early intervention services for first-episode psychosis in the UK. Interviews were transcribed verbatim and thematic analysis was conducted.

Results
Participants believed that the majority of service users with early psychosis experience feelings of loneliness. They often saw socially isolated and disconnected clients and believed them to be lonely, but rarely discussed loneliness explicitly in clinical interactions. A combination of symptoms, stigma and negative sense of self were believed to underpin loneliness. Participants could not identify any specific current interventions delivered by their services for tackling loneliness, but thought some routinely provided interventions, including social groups and psychological treatments, could be helpful. They favoured making a wider range of loneliness interventions available and believed that community agencies beyond mental health services should be involved to make these effective and feasible to deliver. They suggested social participation interventions without an explicit mental health focus as potentially promising and valued a co-produced approach to intervention development.

Conclusions
This study suggests that loneliness is not routinely discussed in early intervention services, and a targeted strategy for tackling it is lacking. Co-produced, individualised community approaches, and interventions that target symptoms, stigma and negative self-schemas might be beneficial in alleviating loneliness for people with early psychosis. Empirical research is needed to develop and test such interventions.
Trends, prevalence and factors associated with hypertension and diabetes among South African adults living with HIV, 2005–2017
Authors: Chiwandire Nicola , Zungu Nompumelelo , Mabaso Musawenkosi , Chasela Charles 
Published: March 2021

Abstract
Background
Many people are now living longer with HIV due to access to antiretroviral treatment. In turn, there has been an increase in the burden of hypertension and diabetes. The paucity of data on the burden of hypertension and diabetes in adults living with HIV in South Africa is a public health concern. The paper aimed to describe the prevalence and factors associated with hypertension and diabetes among adults living with HIV (ALHIV).

Methods
This was a secondary data analysis of the population based on the South African National HIV Prevalence, Incidence, Behaviour and Communication surveys for 2005, 2008 and 2017. Descriptive statistics were used to summarise the characteristics of the study sample. Bivariate and multivariate logistic regression analyses were used to determine factors associated with hypertension and diabetes.

Results
The total study population of ALHIV aged 25 years and older was 978, 1023 and 2483 for 2005, 2008 and 2017. The prevalence of hypertension showed an increasing trend at 11.8% in 2005, 9.5% in 2008 and 14.3% in 2017. The prevalence of diabetes was 3.3% in 2005, 2.8% in 2008 and 3.2% in 2017. Increased odds of hypertension among adults living with HIV were consistently associated with being female and the age group 45 years older across all the survey years, including pensioners and the sick, living in urban areas, high risk of hazardous alcohol consumption, diabetes and heart disease. Increased odds of diabetes were consistently associated with hypertension across all the survey years, including age group 45 years and older, and poor health. While having a secondary level of education and above was protective against diabetes.

Conclusion
The study showed that the prevalence of hypertension is high and has increased over time among adults living with HIV while the prevalence of diabetes has remained constant. Findings identified factors consistently associated with the prevalence of both diseases overtime, including contemporary risk factors that should be targeted in the integrated management of chronic disease and HIV care model.
The association of health-related factors with quality of life among the elderly population in the Jaffna district of Sri Lanka
Authors: Santhalingam Sathees , Sivagurunathan Sivayogan , Prathapan Shamini , Kanagasabai Sivapalan , Kamalarupan Luxmi 
Published: March 2021

Abstract
Background
The proportion of elderly individuals is increasing globally. They should be well cared for to enable them to enjoy their full lifespans. Good health is a vital component of one’s overall quality of life. Our study aimed to assess the association of health-related factors with quality of life among elderly individuals in the Jaffna District of Sri Lanka.

Methods
We conducted a community-based, cross-sectional study among 813 elderly individuals in the Jaffna district of Sri Lanka. Sociodemographic factors and the patterns of health conditions were recorded through an interviewer-administered questionnaire. Quality of life was measured through the World Health Organisation Quality of Life-Bref (WHOQOL-Bref) questionnaire.

Results
There were slightly more male respondents (53.5%) than females in the study. The median age of the participants was 70 (11) years. Approximately one-third of them had at least one chronic health condition. Musculoskeletal complaints were found to be the most common health condition, followed by diabetes, hypertension, vision problems, and asthma. Among the respondents, 20.1% were attending regular follow-up visits in a clinic, and 24% of them were meeting a doctor at least monthly. Among them, 6.8% had at least one limitation in their activities of daily living. However, the majority (58.6%) reported that they were satisfied with their health status. The following factors were found to be significantly associated with worse quality of life: the presence of health conditions, the presence of musculoskeletal conditions, hearing impairment, vision impairment, bronchial asthma, limitations in activities of daily living, and the use of addictive substances. Satisfaction with health, regular follow-up visits in a clinic, meeting a doctor at least monthly, and having diabetes were significantly associated with better quality of life.

Conclusion
Minimising the limitations of daily living, abstaining from using addictive substances, preventing diseases, and improving access to health services may enhance the quality of life of elderly individuals. Furthermore, these factors should be considered by policy makers seeking to improve the quality of life of elderly individuals.
Characterization of hyaluronan-coated extracellular vesicles in synovial fluid of patients with osteoarthritis and rheumatoid arthritis
Authors: Mustonen Anne-Mari , Capra Janne , Rilla Kirsi , Lehenkari Petri , Oikari Sanna , Kääriäinen Tommi , Joukainen Antti , Kröger Heikki , Paakkonen Tommi , Matilainen Johanna , Nieminen Petteri 
Published: March 2021

Abstract
Background
Hyaluronic acid (HA) is the major extracellular matrix glycosaminoglycan with a reduced synovial fluid (SF) concentration in arthropathies. Cell-derived extracellular vesicles (EV) have also been proposed to contribute to pathogenesis in joint diseases. It has recently been shown that human SF contains HA-coated EV (HA–EV), but their concentration and function in joint pathologies remain unknown.

Methods
The aim of the present study was to develop an applicable method based on confocal laser scanning microscopy (CLSM) and image analysis for the quantification of EV, HA-particles, and HA–EV in the SF of the human knee joint. Samples were collected during total knee replacement surgery from patients with end-stage rheumatoid arthritis (RA, n = 8) and osteoarthritis (OA, n = 8), or during diagnostic/therapeutic arthroscopy unrelated to OA/RA (control, n = 7). To characterize and quantify EV, HA-particles, and HA–EV, SF was double-stained with plasma membrane and HA probes and visualized by CLSM. Comparisons between the patient groups were performed with the Kruskal–Wallis analysis of variance.

Results
The size distribution of EV and HA-particles was mostly similar in the study groups. Approximately 66% of EV fluorescence was co-localized with HA verifying that a significant proportion of EV carry HA. The study groups were clearly separated by the discriminant analysis based on the CLSM data. The intensities of EV and HA-particle fluorescences were lower in the RA than in the control and OA groups.

Conclusions
CLSM analysis offers a useful tool to assess HA–EV in SF samples. The altered EV and HA intensities in the RA SF could have possible implications for diagnostics and therapy.
Development of a decision aid to support colorectal cancer screening: perspectives of Asians in an endemic urban community—a qualitative research study
Authors: Yuen Sok Wei Julia , Tay Tsang Yew , Gao Ning , Tho Nian Qin , Tan Ngiap Chuan 
Published: March 2021

AbstractBackgroundColorectal cancer (CRC) is a common malignancy worldwide. Despite being the most common cancer in Singapore, CRC screening rate remains low due to knowledge deficits, social reasons such as inconvenience and a lack of reminder or recommendation. A decision aid (DA) may facilitate an individual’s decision-making to undertake CRC screening by addressing misconceptions and barriers. We postulate that a more person-centred and culturally adapted DA will better serve the local population. The views of the target users are thus needed to develop such a DA. A CRC screening DA prototype has been adapted from an American DA to cater to the Asian users. This study aimed to explore user perspectives on an adapted CRC screening DA-prototype in terms of the design, content and perceived utility.MethodsThe study used in-depth interviews (IDIs) and focus group discussions (FGDs) to gather qualitative data from English-literate multi-ethnic Asian adults aged 50 years old and above. They had yet to screen for CRC before they were recruited from a public primary care clinic in Singapore. The interviews were audio-recorded, transcribed and analysed to identify emergent themes via thematic analysis.ResultsThis study included 27 participants involved in 5 IDI and 5 FGDs. Participants found the DA easily comprehensible and of appropriate length. They appreciated information about the options and proposed having multi-lingual DAs. The design, in terms of the layout, size and font, was well-accepted but there were suggestions to digitalize the DA. Participants felt that the visuals were useful but there were concerns about modesty due to the realism of the illustration. They would use the DA for information-sharing with their family and for discussion with their doctor for decision making. They preferred the doctor’s recommendation for CRC screening and initiating the use of the DA.ConclusionsParticipants generally had favourable perceptions of the DA-prototype. A revised DA will be developed based on their feedback. Further input from doctors on the revised DA will be obtained before assessing its effectiveness to increase CRC screening rate in a randomized controlled trial.
The concept of justifiable healthcare and how big data can help us to achieve it
Authors: van Biesen Wim , Van Der Straeten Catherine , Sterckx Sigrid , Steen Johan , Diependaele Lisa , Decruyenaere Johan 
Published: March 2021

AbstractOver the last decades, the face of health care has changed dramatically, with big improvements in what is technically feasible. However, there are indicators that the current approach to evaluating evidence in health care is not holistic and hence in the long run, health care will not be sustainable. New conceptual and normative frameworks for the evaluation of health care need to be developed and investigated. The current paper presents a novel framework of justifiable health care and explores how the use of artificial intelligence and big data can contribute to achieving the goals of this framework.
A qualitative study of organisational response to national quality standards for 7-day services in English hospitals
Authors: Sutton Elizabeth , Bion Julian , Mannion Russell , Willars Janet , Shaw Elizabeth , Tarrant Carolyn 
Published: March 2021

Abstract
Background
National standards are commonly used as an improvement strategy in healthcare, but organisations may respond in diverse and sometimes negative ways to external quality demands. This paper describes how a sample of NHS hospital trusts in England responded to the introduction of national standards for 7-day services (7DS), from an organisational behaviour perspective.

Methods
We conducted 43 semi-structured interviews with executive/director level and clinical staff, in eight NHS trusts that varied in size, location, and levels of specialist staffing at weekends. We explored approaches to implementing standards locally, and the impact of organisational culture and local context on organisational response.

Results
Senior staff in the majority of trusts described a focus on hitting targets and achieving compliance with the standards. Compliance-based responses were associated with a hierarchical organisational culture and focus on external performance. In a minority of trusts senior staff described mobilising commitment-based strategies. In these trusts senior staff reframed the external standards in terms of organisational values, and used co-operative strategies for achieving change. Trusts that took a commitment-based approach tended to be described as having a developmental organisational culture and a history of higher performance across the board. Audit data on 7DS showed improvement against standards for most trusts, but commitment-focused trusts were less likely to demonstrate improvements on the 7DS audit. The ability of trusts to respond to external standards was limited when they were under pressure due to a history of overall poor performance or resource limitations.

Conclusions
National standards and audit for service-level improvement generate different types of response in different local settings. Approaches to driving improvement nationally need to be accompanied by resources and tailored support for improvement, taking into account local context and organisational culture.
Hybrid mosquitoes? Evidence from rural Tanzania on how local communities conceptualize and respond to modified mosquitoes as a tool for malaria control
Authors: Finda Marceline F. , Okumu Fredros O. , Minja Elihaika , Njalambaha Rukiyah , Mponzi Winfrida , Tarimo Brian B. , Chaki Prosper , Lezaun Javier , Kelly Ann H. , Christofides Nicola 
Published: March 2021

Abstract
Background
Different forms of mosquito modifications are being considered as potential high-impact and low-cost tools for future malaria control in Africa. Although still under evaluation, the eventual success of these technologies will require high-level public acceptance. Understanding prevailing community perceptions of mosquito modification is, therefore, crucial for effective design and implementation of these interventions. This study investigated community perceptions regarding genetically-modified mosquitoes (GMMs) and their potential for malaria control in Tanzanian villages where no research or campaign for such technologies has yet been undertaken.

Methods
A mixed-methods design was used, involving: (i) focus group discussions (FGD) with community leaders to get insights on how they frame and would respond to GMMs, and (ii) structured questionnaires administered to 490 community members to assess awareness, perceptions and support for GMMs for malaria control. Descriptive statistics were used to summarize the findings and thematic content analysis was used to identify key concepts and interpret the findings.

Results
Nearly all survey respondents were unaware of mosquito modification technologies for malaria control (94.3%), and reported no knowledge of their specific characteristics (97.3%). However, community leaders participating in FGDs offered a set of distinctive interpretive frames to conceptualize interventions relying on GMMs for malaria control. The participants commonly referenced their experiences of cross-breeding for selecting preferred traits in domestic plants and animals. Preferred GMMs attributes included the expected reductions in insecticide use and human labour. Population suppression approaches, requiring as few releases as possible, were favoured. Common concerns included whether the GMMs would look or behave differently than wild mosquitoes, and how the technology would be integrated into current malaria control policies. The participants emphasised the importance and the challenge of educating and engaging communities during the technology development.

Conclusions
Understanding how communities perceive and interpret novel technologies is crucial to the design and effective implementation of new vector control programmes. This study offers vital clues on how communities with no prior experience of modified mosquitoes might conceptualize or respond to such technologies when deployed in the context of malaria control programmes. Drawing upon existing interpretive frames and locally-resonant analogies when deploying such technologies may provide a basis for more durable public support in the future.