bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between immune-related adverse events and survival outcomes in Asian patients with advanced melanoma receiving anti-PD-1 antibodies
Authors: Wu Chiao-En , Yang Chan-Keng , Peng Meng-Ting , Huang Pei-Wei , Chang Ching-Fu , Yeh Kun-Yun , Chen Chun-Bing , Wang Chih-Liang , Hsu Chao-Wei , Chen I-Wen , Lin Cheng-Tao , Ueng Shir-Hwa , Lin Gigin , Lin Yu-Fen , Cheng Chi-Yuan , Chang John Wen-Cheng 
Published: October 2020

Abstract
Background
The association between immune-related adverse events (irAEs) and survival outcomes in patients with advanced melanoma receiving therapy with immune checkpoint inhibitors (ICIs) has not been well established, particularly in Asian melanoma.

Methods
We retrospectively reviewed 49 melanoma patients undergoing therapy with ICIs (anti-PD-1 monotherapy), and analyzed the correlation between irAEs and clinical outcomes including progression-free survival (PFS) and overall survival (OS). Results: Overall, the patients who experienced grade 1–2 irAEs had longer PFS (median PFS, 4.6 vs. 2.5 months; HR, 0.52; 95% CI: 0.27–0.98; p = 0.042) and OS (median OS, 15.2 vs. 5.7 months; HR, 0.50; 95% CI: 0.24–1.02; p = 0.058) than the patients who did not experience irAEs. Regarding the type of irAE, the patients with either skin/vitiligo or endocrine irAEs showed better PFS (median PFS, 6.1 vs. 2.7 months; HR, 0.40, 95% CI: 0.21–0.74; p = 0.003) and OS (median OS, 18.7 vs. 4.5 months; HR, 0.34, 95% CI: 0.17–0.69, p = 0.003) than patients without any of these irAEs.

Conclusions
Melanoma patients undergoing anti-PD-1 monotherapy and experiencing mild-to-moderate irAEs (grade 1–2), particularly skin (vitiligo)/endocrine irAEs had favorable survival outcomes. Therefore, the association between irAEs and the clinical outcomes in melanoma patients undergoing anti-PD-1 ICIs may be severity and type dependent.
An immunochemistry-based screen for chemical inhibitors of DNA-protein interactions and its application to human CGGBP1
Authors: Patel Manthan , Patel Divyesh , Datta Subhamoy , Singh Umashankar 
Published: October 2020

Abstract
Background
Inhibition of DNA-binding of proteins by small-molecule chemicals holds immense potential in manipulating the activities of DNA-binding proteins. Such a chemical inhibition of DNA-binding of proteins can be used to modulate processes such as replication, transcription, DNA repair and maintenance of epigenetic states. This prospect is currently challenged with the absence of robust and generic protocols to identify DNA-protein interactions. Additionally, much of the current approaches to designing inhibitors requires structural information of the target proteins.

Methods
We have developed a simple dot blot and immunodetection-based assay to screen chemical libraries for inhibitors of DNA-protein interactions. The assay has been applied to a library of 1685 FDA-approved chemicals to discover inhibitors of CGGBP1, a multifunctional DNA-binding protein with no known structure. Additional in vitro and in cellulo assays have been performed to verify and supplement the findings of the screen.

Results
Our primary screen has identified multiple inhibitors of direct or indirect interactions between CGGBP1 and genomic DNA. Of these, one inhibitor, Givinostat, was found to inhibit direct DNA-binding of CGGBP1 in the secondary screen using purified recombinant protein as the target. DNA and chromatin immunoprecipitation assays reinforced the findings of the screen that Givinostat inhibits CGGBP1-DNA binding.

Conclusions
The assay we have described successfully identifies verifiable inhibitors of DNA-binding of protein; in this example, the human CGGBP1. This assay is customizable for a wide range of targets for which primary antibodies are available. It works with different sources of the target protein, cell lysates or purified recombinant preparations and does not require special equipment, DNA modifications or protein structural data. This assay is scalable and highly adaptable with the potential to discover inhibitors of transcription factors with implications in cancer biology.
Body temperature instability and respiratory morbidity in the very low birth weight infant: a multiple case, intensive longitudinal study
Authors: Ralphe Jane L. , Silva Susan G. , Dail Robin B. , Brandon Debra H. 
Published: October 2020

AbstractBackgroundVery low birth weight (VLBW) infant thermal instability upon neonatal intensive care unit admission has been associated with respiratory morbidity; however, the association between ongoing thermal instability and respiratory morbidity remains unclear.MethodsA longitudinal data analysis was conducted on 12 VLBW infants. Chronic respiratory morbidity risk was defined as supplemental oxygen requirement (FiO2) or scheduled diuretic dosing at 36 weeks post-menstrual age. Acute respiratory morbidity was quantified as desaturations (SpO2<90%), bradycardia with desaturations (HR<100 and SpO2<90%), apnea, increase in FiO2requirement, or increase in respiratory support. Multi-level, mixed-effects models and regression analysis examined the relationships between body temperature over the first 14 days of life and respiratory morbidities.ResultsBody temperature was not associated with chronic respiratory morbidity risk (p=0.2765). Desaturations, bradycardia with desaturations, increased FiO2requirement, and increased respiratory support were associated with decreased body temperature (p<0.05). Apnea was associated with increased body temperature (p<0.05). The covariate-adjusted risk of desaturations (aOR=1.3), bradycardia with desaturations (aOR=2.2), increase in FiO2requirement(aOR=1.2), and increase in respiratory support (aOR=1.2) were significantly greater during episodes of hypothermia.ConclusionVLBW infants are dependent on a neutral thermal environment for optimal growth and development. Therefore, the significant associations between hypothermia and symptoms of acute respiratory morbidity require further study to delineate if these are causal relationships that could be attenuated with clinical practice changes, or if these are concurrent symptoms that cluster during episodes of physiological instability.
The immediate effect of COVID-19 pandemic on children and adolescents with obsessive compulsive disorder
Authors: Nissen J. B. , Højgaard D.R.M.A. , Thomsen P. H. 
Published: October 2020

Abstract
Background
Obsessive compulsive disorder (OCD) is a distressing psychiatric disorder. Traumas may trigger or aggravate OCD symptoms. COVID-19 pandemic has coursed a global crisis and has been associated with onset of psychiatric disorders in adults. Little is known about children/adolescents with OCD. The present study aimed to examine how children/adolescents with OCD react towards COVID-19 crisis.

Methods
A questionnaire was distributed to two separate groups of children/adolescents. One group was a clinical group newly diagnosed at a specialized OCD clinic. All the children/adolescents had a current close contact to a therapist or doctor. The other group was a survey group identified through the Danish OCD Association. Most of these children/adolescents were diagnosed years ago, and their primary treatment was completed. For the clinical group, data from patient files was available.

Results
In both groups, but most pronounced in the survey group, participants experienced a worsening of their OCD, anxiety, and depressive symptoms. The aggravation of OCD correlated with the worsening of anxiety, depressive symptoms, and the extent of avoidance behavior. For both groups, OCD aggressive symptoms predicted a significant worsening. Poor baseline insight showed a trend to predict a symptom worsening. The worsening was most pronounced in children with early age of onset and a family history of attention deficit hyperactivity disorder.

Conclusions
To our knowledge, this is one of the first studies examining the effect of COVID-19 in children/adolescents with OCD. The effect was examined in two separate populations strengthening the findings. The study points towards an influence of the OCD phenotype, baseline insight suggesting a continued vulnerability, and a family history of psychiatric disorders.

Trial registration
The study is approved by the Danish Data Protection Agency (1–16–02-147-20) registered 1st of April 2020. Oral and written information was given to parents and patients and written consent from patients over 15 years and parents were received.
Attenuated self-serving bias in people with internet gaming disorder is related to altered neural activity in subcortical-cortical midline structures
Authors: Wang Yifan , Zheng Li , Wang Chenggong , Guo Xiuyan 
Published: October 2020

Abstract
Background
To protect and maintain the positivity of self-concept, normal people usually show a self-serving bias (internal attribution of positive events and external attribution of negative events) by the motives of self-enhancement and self-protection. Additionally, self-serving assessments predominantly activate the subcortical-cortical midline structures (CMS) in healthy individuals. However, little is known about self-serving bias and its underlying neural correlates among individuals with Internet gaming disorder (IGD).

Methods
Twenty-four participants with IGD and 25 recreational Internet gaming users (RGUs) were scanned while attributing the causes of positive/negative self- and other-related events that could occur in both the game-world and real-world contexts. Region-of-interest (within CMS regions) and parametric analysis were performed to investigate the neural correlates of self-serving bias in IGD.

Results
Behaviorally, the IGD participants attributed more negative and fewer positive events to themselves than RGU participants in both contexts. Neurally, during the attributions of negative events, the IGD participants exhibited increased ventromedial prefrontal cortex (vmPFC) activation in both contexts compared with RGU participants. Higher vmPFC activation was associated with weaker self-protective motivation in the IGD group. Meanwhile, during the attributions of positive events, the IGD participants exhibited decreased precuneus/posterior cingulate cortex activation in the real world compared with RGU participants. Parametric analysis showed a reduced positive correlation between precuneus activation and self-attribution ratings of positive events in the real world in the IGD group relative to the RGU group.

Conclusion
These results suggest that individuals with IGD show an attenuated self-serving bias and altered brain activity within CMS regions involved in self-attribution, providing evidence for the negative self-concept and weakened abilities in both self-enhancement and self-protection in IGD.
Informing the personalisation of interventions for parents of children with conduct problems: a qualitative study
Authors: McKay Kathy , Kennedy Eilis , Senior Rob , Scott Stephen , Hill Jonathan , Doolan Moira , Woolgar Matt , Peeren Siofra , Young Bridget 
Published: October 2020

Abstract
Background
Parenting programmes aim to alleviate behavioural problems in children, including conduct disorder. This study was part of a multi-phase mixed-methods project seeking to extend the reach of parenting programmes for the treatment of conduct problems through developing an evidence base to inform a personalised approach. It explored the narratives of parents of children with behavioural and conduct problems about parenting programmes to identify how such programmes could be personalised in order to extend their reach to parents and children who do not currently benefit.

Methods
Face-to-face semi-structured interviews with a purposive sample of 42 parents, who had different experiences of parenting programmes. Interviews were conversational and informed by a topic guide. Analysis of transcripts of audio-recorded interviews drew on inductive thematic approaches and was framed largely within a phenomenological perspective.

Results
Parents’ accounts demonstrated three themes: 1) a personalised approach needs to include the child; 2) a supportive school matters; and, 3) the programme needs to feel personal. Parents were more likely to have a positive experience at a parenting programme, and for their child to demonstrate positive behavioural changes, when they felt their concerns were validated within the group and they also felt supported by the child’s teachers. Parents whose children had been assessed prior to undertaking the programme were also more likely to perceive the programme to be beneficial, compared to parents who felt their child’s individual issues were never considered.

Conclusions
Our findings point to the potential for personalised approaches to extend the reach of parenting programmes to parents and children who do not currently benefit from such programmes. Important in personalising parenting programmes is assessing children before parents are referred, to directly work with children as well as parents, and to work collaboratively with parents and children to identify which families are most suited to group support or one-to-one support and how this may change depending on circumstances.
Pneumococcal vaccine coverage among individuals aged 18 to 64 years old with underlying medical conditions in the UK: a retrospective database analysis
Authors: Matthews Ian , Lu Xiaoyan , Xia Qian , Black Wynona , Nozad Bayad 
Published: October 2020

Abstract
Background
In the UK certain groups with pre-disposing conditions are eligible for vaccination with the pneumococcal polysaccharide vaccine (PPV23). Uptake of the vaccine in these individuals has not been reported for 10 years. Hence this study investigated the rates of pneumococcal vaccination, the time to vaccination since diagnosis, and factors associated with vaccination in individuals aged 18–64 years with certain underlying medical conditions.

Methods
A retrospective database analysis was conducted using the Clinical Practice Research Datalink (CPRD). Individuals aged 18 to 64 years who had a diagnosis for underlying medical conditions of interest at the index date (January 1, 2011 to December 31, 2015) were included in this study. Both underlying conditions and pneumococcal vaccination were identified using Read codes. A multivariable logistic regression model was used to identify factors associated with pneumococcal vaccination.

Results
A total of 99,153 individuals with underlying medical conditions were included in this study. Within 1 year of follow-up, 13.6% had received pneumococcal vaccination. This figure rose to 32.0% after 4 years of follow-up. The mean time between diagnosis and vaccination was 148.7 days across the overall cohort. Based on multivariate analysis of results, individuals with chronic heart disease, chronic kidney disease, chronic liver disease, chronic respiratory disease or diabetes mellitus were significantly less likely (P < 0.0001) to be vaccinated than those with immunosuppression. Individuals were significantly more likely to receive a pneumococcal vaccination if they received an influenza vaccination in the first year of follow-up than those who did not (P < 0.001).

Conclusions
Despite the Joint Committee on Vaccination and Immunisation (JCVI) recommendations for pneumococcal vaccination in clinical risk groups, rates of pneumococcal vaccination are suboptimal in the UK for individuals aged 18–64 with underlying medical conditions. Further emphasis should be made on the importance of increased pneumococcal vaccination coverage in the UK, given the increased risk of morbidity and mortality associated with indicative underlying medical conditions.
Identifying interventions with Gypsies, Roma and Travellers to promote immunisation uptake: methodological approach and findings
Authors: Dyson Lisa , Bedford Helen , Condon Louise , Emslie Carol , Ireland Lana , Mytton Julie , Overend Karen , Redsell Sarah , Richardson Zoe , Jackson Cath 
Published: October 2020

Abstract
Background
In the UK, Gypsy, Roma and Traveller (GRT) communities are generally considered to be at risk of low or variable immunisation uptake. Many strategies to increase uptake for the general population are relevant for GRT communities, however additional approaches may also be required, and importantly one cannot assume that “one size fits all”. Robust methods are needed to identify content and methods of delivery that are likely to be acceptable, feasible, effective and cost effective. In this paper, we describe the approach taken to identify potential interventions to increase uptake of immunisations in six GRT communities in four UK cities; and present the list of prioritised interventions that emerged.

Methods
This work was conducted in three stages: (1) a modified intervention mapping process to identify ideas for potential interventions; (2) a two-step prioritisation activity at workshops with 51 GRTs and 25 Service Providers to agree a prioritised list of potentially feasible and acceptable interventions for each community; (3) cross-community synthesis to produce a final list of interventions. The theoretical framework underpinning the study was the Social Ecological Model.

Results
Five priority interventions were agreed across communities and Service Providers to improve the uptake of immunisation amongst GRTs who are housed or settled on an authorised site. These interventions are all at the Institutional (e.g. cultural competence training) and Policy (e.g. protected funding) levels of the Social Ecological Model.

Conclusions
The “upstream” nature of the five interventions reinforces the key role of GP practices, frontline workers and wider NHS systems on improving immunisation uptake. All five interventions have potentially broader applicability than GRTs. We believe that their impact would be enhanced if delivered as a combined package. The robust intervention development and co-production methods described could usefully be applied to other communities where poor uptake of immunisation is a concern.

Study registration
Current Controlled Trials ISRCTN20019630, Date of registration 01-08-2013, Prospectively registered.
Patient acceptability of targeted risk-based detection of non-communicable diseases in a dental and pharmacy setting
Authors: Yonel Zehra , Yahyouche Asma , Jalal Zahra , James Alistair , Dietrich Thomas , Chapple Iain L. C. 
Published: October 2020

Abstract
Background
Non-communicable diseases [NCDs] are the major cause of mortality globally and are increasing in prevalence. Different healthcare professionals’ access different population groups; and engaging allied healthcare professionals in risk-driven early case detection of certain NCDs may be beneficial, especially those who have not been tested for NCDs within the previous 12 months.
The objectives of this study were to determine: whether NCD case finding in dental/community pharmacy settings is feasible in terms of patient acceptability, barriers to recruitment, impact on the existing service. Determine time taken to test for: type 2 diabetes risk [T2DM], chronic obstructive pulmonary disease [COPD], hypertension, vitamin D deficiency and chronic kidney disease [CKD]. Determine whether there is added benefit of point of care testing [POCT] to identify diabetes risk compared to a validated screening questionnaire alone.

Methods
An exploratory study was undertaken to explore issues associated with NCD assessment in one dental practice and one community pharmacy within the West-Midlands, UK. Fifty patients > 40 years-of-age were recruited per site. Participants undertook: a questionnaire providing demographic data, any previous NCD diagnosis or positive family history. Validated questionnaires for determining NCD risk [T2DM/COPD]. Chair-side capillary blood [finger-prick] samples for HbA1C, creatinine/eGFR, Vitamin-D.
Prior work had been undertaken to measure the agreement between point of care testing [POCT] devices and a central laboratory method, and to gauge the opinions of participants regarding discomfort experienced using venous (antecubital fossa) and capillary (finger-prick) blood collection, via a 10 cm Visual-Analogue-Scale. The POCT devices demonstrated good concordance with laboratory testing and were acceptable methods of blood collection for participants.

Results
Recruitment rates demonstrated that 8 days were needed to recruit 50 participants and 60% of those approached opted to participate. The principal barrier to participation was time, with average time taken to test being 19mins. Utilising dental and pharmacy settings identified potential cases of previously undiagnosed disease.

Conclusions
Risk-targeted testing for NCDs in high street dental and community pharmacies is both attractive and acceptable to patients.
Formative research to inform the development of a peer-led HIV self-testing intervention to improve HIV testing uptake and linkage to HIV care among adolescents, young people and adult men in Kasensero fishing community, Rakai, Uganda: a qualitative study
Authors: Matovu Joseph K. B. , Nambuusi Aminah , Nakabirye Scovia , Wanyenze Rhoda K. , Serwadda David 
Published: October 2020

AbstractBackgroundDespite efforts to improve HIV testing and linkage to HIV care among adolescents, young people and adult men, uptake rates remain below global targets. We conducted formative research to generate data necessary to inform the design of a peer-led HIV self-testing (HIVST) intervention intended to improve HIV testing uptake and linkage to HIV care in Kasensero fishing community in rural Uganda.MethodsThis qualitative study was conducted in three study communities in Kasensero fishing community in Rakai district, Uganda, in May 2019. Six single-sex focus group discussions (FGDs) comprising 7–8 participants were conducted with adolescents and young people (15–24 years) and adult men (25+ years). We collected data on people’s perceptions about peer-led HIVST; potential acceptability of a peer-led HIVST intervention and suggestions on how to improve linkage to HIV care after a positive HIVST result. Peer-led HIVST was defined as an approach where trained lay people distribute HIVST kits to other people in the community. FGDs were audio-recorded with permission from the participants, transcribed verbatim and analysed manually following a thematic framework approach.ResultsForty-seven participants (31 men and 16 women) participated in the FGDs. Across communities and age-groups, most participants mentioned that peer-led HIVST would be generally acceptable to people in the fishing community but people will need support in performing the test due to fear of performing the test wrongly or failing to cope with HIV-positive results. Most participants felt that peer-led HIVST would bring HIV testing services closer to the community “because [the peer-leader] could be my immediate neighbour”, making it easier for people to obtain the kits at any time of their convenience. To improve linkage to HIV care, participants felt that the use of peer-leaders to deliver the initial ART dose to self-tested HIV-positive individuals would be more preferable to the use of community-based ART groups or home-based ART initiation.ConclusionOur study shows that peer-led HIVST is potentially acceptable in the fishing community. These findings suggest that this approach can improve uptake of HIV testing and linkage to HIV care services among populations that are usually missed through conventional HIV testing services.