bluuebunny/crossref_metadata_2025_split huggingface dataset:
Censcyt: censored covariates in differential abundance analysis in cytometry
Authors: Gerber Reto , Robinson Mark D. 
Published: May 2021

AbstractBackgroundInnovations in single cell technologies have lead to a flurry of datasets and computational tools to process and interpret them, including analyses of cell composition changes and transition in cell states. Thediffcytworkflow for differential discovery in cytometry data consist of several steps, including preprocessing, cell population identification and differential testing for an association with a binary or continuous covariate. However, the commonly measured quantity of survival time in clinical studies often results in a censored covariate where classical differential testing is inapplicable.ResultsTo overcome this limitation, multiple methods to directly include censored covariates in differential abundance analysis were examined with the use of simulation studies and a case study. Results show that multiple imputation based methods offer on-par performance with the Cox proportional hazards model in terms of sensitivity and error control, while offering flexibility to account for covariates. The tested methods are implemented in the packagecenscytas an extension ofdiffcytand are available athttps://bioconductor.org/packages/censcyt.ConclusionMethods for the direct inclusion of a censored variable as a predictor in GLMMs are a valid alternative to classical survival analysis methods, such as the Cox proportional hazard model, while allowing for more flexibility in the differential analysis.
Severe secondary hyperkalemia and arrhythmia from drug interactions between calcium‐channel blocker and voriconazole: a case presentation
Authors: Zhao Xinju , Zhang Chunyan , Zhu Li , Wu Bei , Han Yun , Heung Michael , Zuo Li 
Published: May 2021

Abstract
Background
Patients with kidney disease may have concurrent hypertension and infection. Dihydropyridine calcium-channel blockers (CCB) are the most popular class of antihypertensive drugs used in clinical settings and can be metabolized by cytochrome P450 isoenzyme 3A4 (CYP3A4). Voriconazole is a commonly used antifungal treatment and a CYP3A4-inhibitor. Insufficient attention to drug interactions from the concomitant use of CCB and voriconazole may result in serious adverse reactions.

Case presentation
Here, we report a patient with acute kidney injury on stable anti-neutrophil cytoplasm antibody associated vasculitis who developed hyperkalemia resulting in sinus arrest with junctional escape rhythm attributed to drug interactions of CCB with voriconazole. This is a very rarely reported case and may be an under-recognized complication. After continuous renal replacement therapy and changing the anti-hypertensive drugs, symptoms, and laboratory abnormalities of the patient fully recovered.

Conclusions
This case warns us of severe consequences of drug interactions. Co-prescription of CYP3A4-inhibitors with calcium-channel blockers increases the risk of hypotension and acute kidney injury, which may further induce hyperkalemia and arrhythmia.
Impact of relative dose intensity of oxaliplatin in adjuvant therapy among stage III colon cancer patients on early recurrence: a retrospective cohort study
Authors: Żok Jolanta , Bieńkowski Michał , Radecka Barbara , Korniluk Jan , Adamowicz Krzysztof , Duchnowska Renata 
Published: May 2021

Abstract
Background
Oxaliplatin-based therapy with FOLFOX-4 or CAPOX administered over 6 months remains the standard adjuvant treatment for stage III colon cancer (CC) patients. However, many patients experience dose reduction or early termination of chemotherapy due to oxaliplatin toxicity, which may increase the risk of early recurrence. The objective of this study was to analyze the relationship between the relative dose intensity of oxaliplatin (RDI-O) and early recurrence among stage III CC patients.

Methods
The study included 365 patients treated at five oncology centers in Poland between 2000 and 2014. Survival analysis was performed using the Kaplan-Meier method. Univariate analysis was performed using the Cox proportional hazard model; multivariate analysis was performed with the stepwise forward approach. For all analyses the α level of 0.05 was employed.

Results
The median follow-up was 51.8 months (range 8.2–115.1). Early recurrence < 36 months after surgery occurred in 130 patients (37.8%). In this group 51 (39.2%) and 87 (66.9%) of patients were low and high-risk, respectively. Receipt < 60% of RDI-O was associated with early recurrence within 18 months after surgery (OR = 2.05; 95%CI: 1.18–3.51; p = 0.010), especially in low-risk group (HR = 1.56 (95%CI: 0.96–2.53), p = 0.07). In the multivariate analysis early recurrence was correlated with grade (OR = 2.47; 95% CI: 1.25–4.8; p = 0.008), pN (OR = 2.63; 95% CI: 1.55–4.54; p < 0.001), the number of lymph nodes harvested (OR = 0.51; 95% CI: 0.29–0.86; p = 0.013) and RDI-O (OR = 1.91; 95%CI: 1.06–3.39; p = 0.028). The early vs. late recurrence negatively correlated with OS regardless of the RDI-O (HR = 22.9 (95%CI: 13.9–37.6; p < 0.001).

Conclusions
RDI-O < 60% in adjuvant therapy among stage III CC (especially in low-risk group) increases the risk of early recurrence within 18 months of surgery. Patients with early recurrence showed worse overall survival regardless of the RDI-O.
Exploring the local policy context for reducing health inequalities in children and young people: an in depth qualitative case study of one local authority in the North of England, UK
Authors: Holding Eleanor , Fairbrother Hannah , Griffin Naomi , Wistow Jonathan , Powell Katie , Summerbell Carolyn 
Published: May 2021

Abstract
Background
Improving children and young people’s (CYP) health and addressing health inequalities are international priorities. Reducing inequalities is particularly pertinent in light of the Covid-19 outbreak which has exacerbated already widening inequalities in health. This study aimed to explore understandings of inequality, the anticipated pathways for reducing inequalities among CYP and key factors affecting the development and implementation of policy to reduce inequalities among CYP at a local level.

Methods
We carried out a qualitative case study of one local government region in the North of England (UK), comprising semi structured interviews (n = 16) with service providers with a responsibility for child health, non-participant observations of key meetings (n = 6 with 43 participants) where decisions around child health are made, and a local policy documentation review (n = 11). We employed a novel theoretical framework, drawing together different approaches to understanding policy, to guide our design and analysis.

Results
Participants in our study understood inequalities in CYP health almost exclusively as socioeconomically patterned inequalities in health practices and outcomes. Strategies which participants perceived to reduce inequalities included: preventive support and early intervention, an early years/whole family focus, targeted working in local areas of high deprivation, organisational integration and whole system/place-based approaches. Despite demonstrating a commitment to a social determinants of health approach, efforts to reduce inequalities were described as thwarted by the prevalence of poverty and budget cuts which hindered the ability of local organisations to work together. Participants critiqued national policy which aimed to reduce inequalities in CYP health for failing to recognise local economic disparities and the interrelated nature of the determinants of health.

Conclusions
Despite increased calls for a ‘whole systems’ approach to reducing inequalities in health, significant barriers to implementation remain. National governments need to work towards more joined up policy making, which takes into consideration regional disparities, allows for flexibility in interpretation and addresses the different and interrelated social determinants of health. Our findings have particular significance in light of Covid-19 and indicate the need for systems level policy responses and a health in all policies approach.
Temporal summation of mechanical pain prospectively predicts movement-evoked pain severity in adults with chronic low back pain
Authors: Overstreet Demario S. , Michl Ava N. , Penn Terence M. , Rumble Deanna D. , Aroke Edwin N. , Sims Andrew M. , King Annabel L. , Hasan Fariha N. , Quinn Tammie L. , Long D. Leann , Sorge Robert E. , Goodin Burel R. 
Published: May 2021

Abstract
Background
Biopsychosocial factors above and beyond pathoanatomical changes likely contribute to the severity of chronic low back pain. A pro-nociceptive endogenous pain modulatory balance (↓inhibition and ↑facilitation) may be an important contributor to chronic low back pain severity and physical function; however, additional research is needed to address this possibility. The objective of this study was to determine whether quantitative sensory tests of endogenous pain inhibition and facilitation prospectively predict movement-evoked pain and cLBP severity self-reported on a validated questionnaire.

Methods
One hundred thirty-four individuals with chronic low back pain were enrolled in this two-session study. During the first study session, temporal summation of mechanical pain and conditioned pain modulation were assessed at the lumbar spine to determine endogenous pain facilitation and inhibition, respectively. One week later, participants returned for a second study session whereby they reported their pain severity and pain interference using the Brief Pain Inventory-Short Form. Movement-evoked pain and physical function capacity were assessed upon completion of the balance, walking, and transition from sit to stand tests of the Short Physical Performance Battery.

Results
Temporal summation of mechanical pain, but not conditioned pain modulation, significantly and prospectively predicted greater movement-evoked pain and poorer physical function on the Short Physical Performance Battery. Neither temporal summation nor conditioned pain modulation were significantly related to self-reported pain severity or pain interference on the Brief Pain Inventory-Short Form.

Conclusions
Findings suggest that a pro-nociceptive pain modulatory balance characterized by enhanced pain facilitation may be an important driver of movement-evoked pain severity and poor physical function in individuals with chronic low back pain.
Why clinical training in China should improve: a cross-sectional study of MD graduates
Authors: Zhang Xiaoning , Li Chong , Yue Cailing , Jiang Xue , Cao Junli , ten Cate Olle 
Published: May 2021

Abstract
Background
China is experiencing major medical education reforms that include establishing national training standards, standards for health professionals, and advanced health delivery system requirements. Graduate medical education (GME) is being piloted as a merger of Doctor of Medicine (MD) with PhD programs to improve academic research and clinical training. However, the academic degree-centred system has led to a preoccupation with research rather than clinical training. Unfortunately, there is a shortage of quality information regarding the clinical training of MD graduates from Chinese medical schools. To fill this gap, this general investigation aims to provide the perspective of recent MD graduates in China for the different subspecialties of clinical training as experienced in different contexts.

Methods
There were 432 MD graduates who participated in an online survey regarding their clinical training. Information collected included overall satisfaction, educational supervision, supervised learning events, curriculum coverage, local teaching, teamwork, educational governance, workload, supportiveness of the environment, feedback, clinical experience, patient safety, handovers, and reporting systems.

Results
Only 37.4% reported satisfaction with the overall clinical training quality; 54.6% rated the informal and bedside quality as “good”; 64.4% reported they knew who provided clinical supervision; but only 35.5% rated the quality of clinical supervision as high; 51.8% reported that they judged senior physicians as “not competent”; 41.9% agreed that the staff treated each other respectfully; 97.4% admitted that they worked beyond the mandatory hours and claimed they were regularly short of sleep; 84.2% raised concerns about patient safety; 45.3% reported that they received regular informal feedback; 48.1% believed that their concerns about education and training would be addressed.

Conclusions
This study suggests that the quality of clinical training for MD graduates should be improved. While the overall satisfaction with the teaching quality was acceptable, the quality of many clinical training aspects scored poorly. A major problem seems an undue focus on research in MD/PhD training at the cost of the quality of clinical training, due to career perspectives that undervalue clinical competence. The findings of this study should benefit from a deeper investigation to understand the causes and possible remediation. Suggestions include defining subspecialties and training lengths; monitoring, evaluation, and integration SST with MD degree; providing funds or rewards for academic and clinical training; establishing supervising teams to guide clinical training; and establishing physician scientist task force to help overcome challenges.
The experiences, attitudes and understanding of research amongst medical students at an Australian medical school
Authors: Muhandiramge Jaidyn , Vu Tony , Wallace Megan J. , Segelov Eva 
Published: May 2021

Abstract
Background
Research engagement plays an integral role in developing clinicians that practice effective, evidence-based medicine. Research participation by clinicians, however, is declining. Given the link between research during medical school and future research output, promotion of medical student research is one avenue by which this shortage can be addressed. Student research attitudes and participation in Australia are not well-documented in the literature. This study therefore aims to investigate research practices, motivators, and barriers amongst Australian medical students in order to determine whether there is a need for further integration of research within Australian medical school curriculums.

Methods
A cross-sectional study design was used to explore research experience and attitudes, as well as the enablers and barriers to research amongst students enrolled in all years of the five-year medical course at Monash University. A questionnaire was created by combining questions from several surveys on medical student research and comprised Likert scales, multiple choice options and free-text responses assessing research experience, attitudes, motivators, and barriers.

Results
Seven hundred and four respondents (69.4% female; survey response rate 36.7%) reported variable research experience and interest. Less than half of the cohort (n = 296; 44.9%) had contributed to a research project. Increasing employability for specialty training programs was the primary motivating factor (n = 345; 51.9%) for pursuing research, with only 20.5% (n = 136) citing an interest in academia as a motivator. Time constraints (n = 460; 65.3%) and uncertainty surrounding how to find research opportunities (n = 449; 63.8%) were the most common barriers to research.

Conclusions
Medical students at Monash University are interested in but have limited experience with research. Students are, however, primarily motivated by the prospect of increasing employability for specialist training; medical schools should therefore focus on encouraging intrinsic motivation for pursuing research. Greater integration of research education and opportunities within medical school curricula may also be required to provide students with the skills necessary to both pursue research and practice evidence-based medicine.
Stigma about mental disease in Portuguese medical students: a cross-sectional study
Authors: Moreira Ana-Raquel , Oura Maria-Joao , Santos Paulo 
Published: May 2021

Abstract
Background
The stigma about mental diseases is common in the population and also in medical students, where it may condition their future practice and the way they deal with these patients.

Aim
To evaluate and characterize the stigma on mental diseases in Portuguese sixth-year medical students, based on a clinical scenario of a classmate suffering from a mental disorder.

Methods
Observational cross-sectional study, involving sixth-year students of all Portuguese medical schools. We applied an online self-response questionnaire, using the Portuguese version of the Attribution Questionnaire AQ-9, and a vignette of a classmate colleague, presenting mental illness symptoms. Stigma scores were calculated. We used logistic regression to estimate the effect of social determinants on stigma pattern, and we analysed the correlation between 9 variables evaluated by the AQ-9 and total stigma.

Results
A total of 501 participants were included for analysis (69.5% females, median age of 24 years old). Medical students were available to help in the proposed clinical scenario (6.93/9.00; 95%CI:6.77–7.10), if necessary using coercion for treatment (3.85; 95%CI:3.63–4.07), because they felt pity (6.86; 95%CI:6.67–7.06) and they perceived some kind of dangerousness (4.06; 95%CI:3.84–4.28). Stigma was lower in students having a personal history of mental illness (OR:0.498; 95%CI:0.324–0.767; p = 0.002) and in those with positive familial history (OR: 0.691; 95%CI:0.485–0.986; p = 0.041).

Conclusion
Our results show the importance of implementing anti-stigma education, to improve medical students’ attitudes towards peers living with mental diseases.
Precision medicine and the principle of equal treatment: a conjoint analysis
Authors: Tranvåg Eirik Joakim , Strand Roger , Ottersen Trygve , Norheim Ole Frithjof 
Published: May 2021

Abstract
Background
In precision medicine biomarkers stratify patients into groups that are offered different treatments, but this may conflict with the principle of equal treatment. While some patient characteristics are seen as relevant for unequal treatment and others not, it is known that they all may influence treatment decisions. How biomarkers influence these decisions is not known, nor is their ethical relevance well discussed.

Methods
We distributed an email survey designed to elicit treatment preferences from Norwegian doctors working with cancer patients. In a forced-choice conjoint analysis pairs of hypothetical patients were presented, and we calculated the average marginal component effect of seven individual patient characteristics, to estimate how each of them influence doctors’ priority-setting decisions.

Results
A positive biomarker status increased the probability of being allocated the new drug, while older age, severe comorbidity and reduced physical function reduced the probability. Importantly, sex, education level and smoking status had no significant influence on the decision.

Conclusion
Biomarker status is perceived as relevant for priority setting decisions, alongside more well-known patient characteristics like age, physical function and comorbidity. Based on our results, we discuss a framework that can help clarify whether biomarker status should be seen as an ethically acceptable factor for providing unequal treatment to patients with the same disease.
Implementing a telehealth prehabilitation education session for patients preparing for major cancer surgery
Authors: Waterland Jamie L. , Chahal Rani , Ismail Hilmy , Sinton Catherine , Riedel Bernhard , Francis Jill J. , Denehy Linda 
Published: May 2021

Abstract
Background
Prehabilitation services assist patients in preparing for surgery, yet access to these services are often limited by geographical factors. Enabling rural and regional patients to access specialist surgical prehabilitation support with the use of telehealth technology has the potential to overcome health inequities and improve post-operative outcomes.

Aim
To evaluate the current and likely future impact of a telehealth preoperative education package for patients preparing for major abdominal cancer surgery.

Methods
A telehealth alternative to a hospital based pre-operative education session was developed and implemented at a dedicated cancer hospital. Adult patients (≥18 years) scheduled for elective major cancer surgery were offered this telehealth alternative. Impact evaluation was conducted using the RE-AIM framework.

Results
To date, 35 participants have consented to participate in the study. Thirty-one participants attended the intervention; 24 (69%) residing in rural or regional areas. Twenty-four (77%) reported that if given a choice they would prefer the online session as opposed to attending the hospital in person. The majority (97%) reported they would recommend the intervention to others preparing for surgery. Session information was recalled by all 26 participants and 77% of participants reported acting on recommendations 2 weeks after the session. Lessons learnt and recommendations for providers implementing similar programs are reported.

Conclusion
Telehealth alternatives to hospital based pre-operative education are well received by patients preparing for major cancer surgery. We make seven recommendations to improve implementation. Further evaluation of implementation strategies alongside clinical effectiveness in future studies is essential.

Trial registration
ACTRN12620000096954, 04/02/2020.
Recent advances in near-infrared II imaging technology for biological detection
Authors: Zhang Nan-nan , Lu Chen-ying , Chen Min-jiang , Xu Xiao-ling , Shu Gao-feng , Du Yong-zhong , Ji Jian-song 
Published: May 2021

AbstractMolecular imaging technology enables us to observe the physiological or pathological processes in living tissue at the molecular level to accurately diagnose diseases at an early stage. Optical imaging can be employed to achieve the dynamic monitoring of tissue and pathological processes and has promising applications in biomedicine. The traditional first near-infrared (NIR-I) window (NIR-I, range from 700 to 900 nm) imaging technique has been available for more than two decades and has been extensively utilized in clinical diagnosis, treatment and scientific research. Compared with NIR-I, the second NIR window optical imaging (NIR-II, range from 1000 to 1700 nm) technology has low autofluorescence, a high signal-to-noise ratio, a high tissue penetration depth and a large Stokes shift. Recently, this technology has attracted significant attention and has also become a heavily researched topic in biomedicine. In this study, the optical characteristics of different fluorescence nanoprobes and the latest reports regarding the application of NIR-II nanoprobes in different biological tissues will be described. Furthermore, the existing problems and future application perspectives of NIR-II optical imaging probes will also be discussed.