bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene-set distance analysis (GSDA): a powerful tool for gene-set association analysis
Authors: Cao Xueyuan , Pounds Stan 
Published: April 2021

AbstractBackgroundIdentifying sets of related genes (gene sets) that are empirically associated with a treatment or phenotype often yields valuable biological insights. Several methods effectively identify gene sets in which individual genes have simple monotonic relationships with categorical, quantitative, or censored event-time variables. Some distance-based methods, such as distance correlations, may detect complex non-monotone associations of a gene-set with a quantitative variable that elude other methods. However, the distance correlations have yet to be generalized to associate gene-sets with categorical and censored event-time endpoints. Also, there is a need to determine which genes empirically drive the significance of an association of a gene set with an endpoint.ResultsWe develop gene-set distance analysis (GSDA) by generalizing distance correlations to evaluate the association of a gene set with categorical and censored event-time variables. We also develop a backward elimination procedure to identify a subset of genes that empirically drive significant associations. In simulation studies, GSDA more effectively identified complex non-monotone gene-set associations than did six other published methods. In the analysis of a pediatric acute myeloid leukemia (AML) data set, GSDA was the only method to discover that event-free survival (EFS) was associated with the 56-gene AML pathway gene-set, narrow that result down to 5 genes, and confirm the association of those 5 genes with EFS in a separate validation cohort. These results indicate that GSDA effectively identifies and characterizes complex non-monotonic gene-set associations that are missed by other methods.ConclusionGSDA is a powerful and flexible method to detect gene-set association with categorical, quantitative, or censored event-time variables, especially to detect complex non-monotonic gene-set associations. Available athttps://CRAN.R-project.org/package=GSDA.
The BioCyc Metabolic Network Explorer
Authors: Paley Suzanne , Karp Peter D. 
Published: April 2021

Abstract
Background
The Metabolic Network Explorer is a new addition to the BioCyc.org website and the Pathway Tools software suite that supports the interactive exploration of metabolic networks. Any metabolic network visualization tool must by necessity show only a subset of all possible metabolite connections, or the results will be visually overwhelming. Existing tools, even those that purport to show an organism’s full metabolic network, limit the set of displayed connections based on predefined pathways or other preselected criteria. We sought instead to provide a tool that would give the user dynamic control over which connections to follow.

Results
The Metabolic Network Explorer is an easy-to-use, web-based software tool that allows the user to specify a starting metabolite of interest and interactively explore its immediate metabolic neighborhood in either or both directions to any desired depth, letting the user select from the full set of connected reactions. Although, as for other tools, only a small portion of the metabolic network is visible at a time, that portion is selected by the user, based on the full reaction complement, and it is easy to switch among alternate paths of interest. The display is intuitive, customizable, and provides copious links to more detailed information pages.

Conclusions
The Metabolic Network Explorer fills a gap in the set of metabolic network visualization tools and complements other modes of exploration. Its primary strengths are its ease of use, diagrams that are intuitive to biologists, and its integration with the broader corpus of data provided by a BioCyc Pathway/Genome Database.
Using CPAP in COVID-19 patients outside of the intensive care setting: a comparison of survival and outcomes between dialysis and non-dialysis dependent patients
Authors: Floyd Lauren , Stauss Madelena , Storrar Joshua , Vanalia Parthvi , France Anna , Dhaygude Ajay 
Published: April 2021

Abstract
Background
SARS-CoV-2 (COVID-19) is a novel coronavirus associated with high mortality rates. The use of Continuous Positive Airway Pressure (CPAP) has been recognised as a management option for severe COVID-19 (NHS, Specialty guides for patient management during the coronavirus pandemic Guidance for the role and use of non-invasive respiratory support in adult patients with coronavirus (confirmed or suspected), https://www.nice.org.uk/guidance/ng159). We offered ward-based CPAP to COVID-19, dialysis patients not suitable for escalation to ICU. The aim of the study was to evaluate the use of CPAP for COVID-19 dialysis patients compared to non-dialysis COVID-19 patients outside of the intensive care setting. We further aimed to investigate factors associated with improved outcomes.

Methods
Data was collected from a single centre (Royal Preston Hospital, UK), from March to June 2020. Treatment outcomes were compared for dialysis and non-dialysis dependent patients who received CPAP with limitations on their escalation and resuscitation status. Kaplan-Meier survival curves and Cox regression models were used to compare outcomes. The primary study outcome was 30 day mortality. Confounders including length of admission, systemic anticoagulation and ultrafiltration volumes on dialysis were also analysed.

Results
Over the study period, 40 dialysis patients tested positive for COVID-19, with 30 requiring hospital admission. 93% (n = 28) required supplementary oxygen and 12% (n = 9) required CPAP on the ward. These patients were compared to a serial selection of 14 non-dialysis patients treated with CPAP during the same period. Results showed a significant difference in 30 day survival rates between the two groups: 88.9% in the dialysis group vs. 21.4% in the non-dialysis group. Statistical modelling showed that anticoagulation was also an important factor and correlated with better outcomes.

Conclusion
This is to the best of our knowledge, the largest series of COVID-19 dialysis patients treated with CPAP in a ward-based setting. In general, dialysis dependent patients have multiple co-morbidities including cardiovascular disease and diabetes mellitus making them vulnerable to COVID-19 and not always suitable for treatment in ICU. We showed a significantly lower 30 day mortality rate with the use of CPAP in the dialysis group (11.1%) compared to the non-dialysis group (78.6%). Despite a small sample size, we believe this study provides impetus for further work clarifying the role of CPAP in treating COVID-19 dialysis dependent patients.
Aging-associated inflammation and fibrosis in arachnoid membrane
Authors: Suzuki Hime , Mikami Takeshi , Iwahara Naotoshi , Akiyama Yukinori , Wanibuchi Masahiko , Komatsu Katsuya , Yokoyama Rintaro , Hirano Tsukasa , Hosoda Ryusuke , Horio Yoshiyuki , Kuno Atsushi , Mikuni Nobuhiro 
Published: April 2021

Abstract
Background
The physiological and pathological significance of the arachnoid membrane (AM) is still unknown. In this study, we investigated various characteristics of the AM, focusing on the influence of inflammation and fibrosis.

Methods
Small pieces of AM sample were obtained during neurosurgical procedures from 74 cases. The clinical and pathological characteristics of the hyperplastic AM group (≥ 50 μm) and the non-hyperplastic AM group (< 50 μm) were compared. Then, potential correlations between AM thickness and clinical characteristics were analyzed. Moreover, VEGFα, TGFβ, and TGFα levels were quantitated by real time PCR. Then, the potential correlations between AM thickness and these inflammatory or anti-inflammatory markers, and the influence of the original disease were calculated.

Results
The median age of the patients in hyperplastic AM group was significantly older than that of the non-hyperplastic AM group. Moreover, the number of fibroblasts, CD68+ cells, CD86+ cells, and CD206+ cells in the hyperplastic AM group was significantly higher than that in the non-hyperplastic AM group. The AM thickness was significantly correlated to age and number of fibroblasts, CD68+ cells, CD86+ cells, and CD206+ cells. The thickness of the AM was significantly correlated to the messenger RNA expression levels of VEGFα (ρ = 0.337), and the VEGFα expression levels were significantly correlated with TGFβ and TNFα.

Conclusions
The AM hyperplasia was influenced by aging and could be a result of inflammation and fibrosis through cytokine secretion from the inflammatory cells and fibroblasts in the AM.
Effect of the CRADLE vital signs alert device intervention on referrals for obstetric haemorrhage in low-middle income countries: a secondary analysis of a stepped- wedge cluster-randomised control trial
Authors: Giblin Lucie , Vousden Nicola , Nathan Hannah , Gidiri Francis , Goudar Shivaprasad , Charantimath Umesh , Sandall Jane , Seed Paul T. , Chappell Lucy C. , Shennan Andrew H. 
Published: April 2021

Abstract
Background
Obstetric haemorrhage is the leading cause of maternal death worldwide, 99% of which occur in low and middle income countries. The majority of deaths and adverse events are associated with delays in identifying compromise and escalating care. Management of severely compromised pregnant women may require transfer to tertiary centres for specialised treatment, therefore early recognition is vital for efficient management. The CRADLE vital signs alert device accurately measures blood pressure and heart rate, calculates the shock index (heart rate divided by systolic blood pressure) and alerts the user to compromise through a traffic light system reflecting previously validated shock index thresholds.

Methods
This is a planned secondary analysis of data from the CRADLE-3 trial from ten clusters across Africa, India and Haiti where the device and training package were randomly introduced. Referral data were prospectively collected for a 4-week period before, and a 4-week period 3 months after implementation. Referrals from primary or secondary care facilities to higher level care for any cause were recorded. The denominator was the number of women seen for maternity care in these facilities.

Results
Between April 1 2016 and Nov 30th, 2017 536,223 women attended maternity care facilities. Overall, 3.7% (n = 2784/74,828) of women seen in peripheral maternity facilities were referred to higher level care in the control period compared to 4.4% (n = 3212/73,371) in the intervention period (OR 0.89; 0.39–2.05) (data for nine sites that were able to collect denominator). Of these 0.29% (n = 212) pre-intervention and 0.16% (n = 120) post-intervention were referred to higher-level facilities for maternal haemorrhage. Although overall referrals did not significantly reduce there was a significant reduction in referrals for obstetric haemorrhage (OR 0.56 (0.39–0.65) following introduction of the device with homogeneity (i-squared 26.1) between sites. There was no increase in any bleeding-related morbidity (maternal death or emergency hysterectomy).

Conclusions
Referrals for obstetric haemorrhage reduced following implementation of the CRADLE Vital Signs Alert Device, occurring without an increase in maternal death or emergency hysterectomy. This demonstrates the potential benefit of shock index in management pathways for obstetric haemorrhage and targeting limited resources in low- middle- income settings.

Trial registration
This study is registered with the ISRCTN registry, number ISRCTN41244132 (02/02/2016).
Clinical outcomes observation in stage IIB–IIIB cervical cancer treated by adjuvant surgery following concurrent chemoradiotherapy
Authors: Li Yong , Chen Zhiying , Wang Xiang , Li Xiumei , Zhou Jie , Zhang Yongchun 
Published: April 2021

AbstractBackgroundTo explore the feasibility of adjuvant surgery following concurrent chemoradiation therapy (CCRT) in stage IIB–IIIB (according to FIGO staging of 2009) cervical cancer and analyze risk factors of recurrence after surgery.MethodsForty-nine patients diagnosed with stage IIB–IIIB cervical cancer were reviewed retrospectively. We investigated the risk factors of recurrence after surgery using Chi-squared Test and further analyzed multiple factors affecting postoperative recurrence using the multi-factor logistic regression. Furthermore, the correlation of surgery outcomes (including operation time, bleeding, and hospitalization date and surgery complications) with the time which carried out between CCRT and completion surgery was analyzed.ResultsTumor histology and residual tumor in the cervix were significantly associated with postoperative recurrence (P = 0.014 andP = 0.040, respectively). Logistic regression analysis demonstrated that the independent risk factors of postoperative recurrence were age and residual tumor in the cervix (P = 0.017 andP = 0.030, respectively). Complications (operation time, bleeding, hospitalization date) were compared between patients with an interval with radiotherapy less than 6 weeks and patients with an interval longer than 6 weeks. There were statistical differences in the amount of bleeding and postoperative complications between the two groups (P = 0.019 andP = 0.044, respectively).ConclusionCCRT combined with surgery for stage IIB–IIIB cervical cancer was feasible, reduced the rate of postoperative recurrence and surgery complications were tolerated.
Intrinsic and extrinsic apoptosis responses in leukaemia cells following daunorubicin treatment
Authors: Al-Aamri Hussain Mubarak , Irving Helen R. , Bradley Christopher , Meehan-Andrews Terri 
Published: April 2021

AbstractBackgroundDaunorubicin is used clinically in the treatment of myeloma, acute lymphatic and myelocytic leukaemia. The toxic lesions caused by daunorubicin induce various modes of cell death, including apoptosis. Apoptosis is highly regulated programmed cell death that can be initiated mainly via two pathways, through death receptors (extrinsic) or involvement of the mitochondria (intrinsic). Induction of apoptosis via these pathways has been alluded following treatment with daunorubicin, but never compared in acute lymphoblastic leukaemia over a time course.MethodsThis study investigated the mechanisms of daunorubicin induced apoptosis in the treatment of CCRF-CEM, MOLT-4 (acute T-lymphoblastic leukaemia) and SUP-B15 (acute B-lymphoblastic leukaemia) cells. Cells were treated with daunorubicin for 4 h, and then placed in recovery medium (without daunorubicin) for 4 h, 12 h and 24 h. Apoptotic response was analysing using annexin-V expression, caspase activity, mitochondrial membrane potential change and an array to detect 43 apoptotic proteins.ResultsDaunorubicin induced apoptosis in all leukemic cell lines, but with different levels and duration of response. Both apoptosis levels and caspase activity increased after four hours recovery then declined in CCRF-CEM and MOLT-4 cells. However, SUP-B15 cells displayed initially comparable levels but remained elevated over the 24 h assessment period. Changes in mitochondrial membrane potential occurred in both MOLT-4 and CCRF-CEM cells but not in SUP-B15 cells. Expression of apoptotic proteins, including Bcl-2, Bax, caspase 3 and FADD, indicated that daunorubicin potentially induced both extrinsic and intrinsic apoptosis in both CCRF-CEM and MOLT-4 cells, but only extrinsic apoptosis in SUP-B15 cells.ConclusionsThis study describes variations in sensitivities and timing of apoptotic responses in different leukaemia cell lines. These differences could be attributed to the lack of functional p53 in coordinating the cells response following cytotoxic treatment with daunorubicin, which appears to delay apoptosis and utilises alternative signalling mechanisms that need to be further explored.
Improving knowledge, attitudes and practice to prevent COVID-19 transmission in healthcare workers and the public in Thailand
Authors: Maude Rapeephan R. , Jongdeepaisal Monnaphat , Skuntaniyom Sumawadee , Muntajit Thanomvong , Blacksell Stuart D. , Khuenpetch Worarat , Pan-Ngum Wirichada , Taleangkaphan Keetakarn , Malathum Kumtorn , Maude Richard James 
Published: April 2021

AbstractBackgroundKey infection prevention and control measures to limit transmission of COVID-19 include social distancing, hand hygiene, use of facemasks and personal protective equipment. However, these have limited or no impact if not applied correctly through lack of knowledge, inappropriate attitude or incorrect practice. In order to maximise the impact of infection prevention and control measures on COVID-19 spread, we undertook a study to assess and improve knowledge, attitudes and practice among 119 healthcare workers and 100 general public in Thailand. The study setting was two inpatient hospitals providing COVID-19 testing and treatment. Detailed information on knowledge, attitudes and practice among the general public and healthcare workers regarding COVID-19 transmission and its prevention were obtained from a combination of questionnaires and observations.ResultsKnowledge of the main transmission routes, commonest symptoms and recommended prevention methods was mostly very high (> 80%) in both groups. There was lower awareness of aerosols, food and drink and pets as sources of transmission; of the correct duration for handwashing; recommended distance for social/physical distancing; and about recommended types of face coverings. Information sources most used and most trusted were the workplace, work colleagues, health workers and television. The results were used to produce a set of targeted educational videos which addressed many of these gaps with subsequent improvements on retesting in a number of areas. This included improvements in handwashing practice with an increase in the number of areas correctly washed in 65.5% of the public, and 57.9% of healthcare workers. The videos were then further optimized with feedback from participants followed by another round of retesting.ConclusionsDetailed information on gaps in knowledge, attitudes and practice among the general public and healthcare workers regarding COVID-19 transmission and its prevention were obtained from a combination of questionnaires and observations. This was used to produce targeted educational videos which addressed these gaps with subsequent improvements on retesting. The resulting videos were then disseminated as a resource to aid in efforts to fight COVID-19 in Thailand and worldwide.
A cross-sectional study of opioid involvement in non-poisoning suicide – risks and prevention opportunities
Authors: Mason Maryann , Welch Sarah B. , McLone Suzanne , Bartell Tami , Lank Patrick M. , Sheehan Karen , Post Lori Ann 
Published: April 2021

Abstract
Objective
To examine prevalence, demographic, and incident factors associated with opioid-positivity in Illinois suicide decedents who died by causes other than poisoning.

Method
Cross-sectional study of Illinois’ suicide decedents occurring between January 2015 and December 2017. Data come from the National Violent Death Reporting System. We used Chi-square tests to compare decedent and incident circumstance characteristics by opioid toxicology screen status. Incident narratives were analyzed to obtain physical and mental health histories and circumstances related to fatal injury events.

Results
Of 1007 non-poisoning suicide decedents screened for opioids, 16.4% were opioid-positive. White race, age 75 and over, and widowed or unknown marital status were associated with opioid-positivity. Among opioid-positive decedents, 25% had a history of substance use disorder (SUD), 61% depression, and 19% anxiety. The majority (52%) of opioid-positive decedents died by firearm, a higher percentage than opioid-negative decedents.

Conclusion
The opioid overdose crisis largely has not overlapped with non-poisoning suicide in this study. Overall, our analyses have not identified additional risk factors for suicide among opioid-positive suicide decedents. However, the overlap between opioid-positivity, SUD, and physical and mental health problems found among decedents in our data suggest several suicide prevention opportunities. These include medication assisted treatment for SUD which has been shown to reduce suicide, screening for opioid/benzodiazepine overlap, and limiting access to lethal means during opioid use. Improved death scene investigations for substances and use of the Prescription Drug Monitoring Program to document prescriptions are needed to further understanding of the role of substances in non-poisoning suicide.
Empathy and attitude toward communication skill learning as a predictor of patient-centered attitude: a cross-sectional study of dental students in Korea
Authors: Lee Minjung , Ihm Jungjoon 
Published: April 2021

Abstract
Background
Enhancing medical students’ practice of patient-centered care is a goal of medical schools. In addition to exploring the demographic and academic factors of the students, it is necessary to identify other attitudes and perceptions that may influence the student’s patient-centered attitude and inclination toward communication skill learning. This study aimed to assess patient-centered attitudes among dental students in Korea and identify the association between the students’ characteristics and empathy, communication skill learning attitude, and patient-centered attitude.

Methods
Data were collected via a cross-sectional online survey, and 312 dental students were included in the analyses. The study participants completed the Patient–Practitioner Orientation Scale (PPOS), the Interpersonal Reactivity Index (IRI), and the Communication Skills Attitude Scale (CSAS). Analyses were performed using independent samples’ t-tests, hierarchical multi-variable regression, and ANOVA with a post-hoc Tukey test.

Results
The students tend to be moderately patient-oriented toward the sharing subscale of PPOS score (M = 3.78, standard deviation [SD] = 0.54) and slightly more patient-centered toward the caring subscale of PPOS score (M = 4.41, SD = 0.52) of patient-centered attitudes. Being a female and a shorter academic period in dentistry were associated with attitudes toward patient-centered care. Empathy and positive attitude toward learning communication skills were also related to a patient-centered attitude, and among aspects of empathy, “empathic concern” had the greatest significant impact on patient-centered attitude.

Conclusions
Gender, academic period, empathy, and attitudes on learning communication skills were important influencing factors of patient-centered attitudes. Patient-centered attitude can and must be taught. Education programs should focus on enhancing empathy, emphasizing positive attitudes on learning communication skills, and conducting follow-up educational sessions to prevent students from becoming less patient-centered with an increase in duration of their academic period.