bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using the United Kingdom standards for public involvement to evaluate the impact of public involvement in a multinational clinical study
Authors: Seddon Kathy , Elliott Jim , Johnson Miriam , White Clare , Watson Max , Nelson Annmarie , Noble Simon 
Published: April 2021

Abstract
Background
The publication of the United Kingdom (UK) Standards for Public Involvement (PI) (UK Standards) in research drew a clear line in the sand regarding the importance of utilising the unique experience, skills and expertise that lay people may offer to the development, conduct and dissemination of clinical research. The UK Standards provide a benchmark which researchers should aim to achieve, yet its implementation continues to be a step wise iterative process of change management. A recent evaluation by a regional research group has suggested that our understanding of PI is enhanced through reflection on the UK Standards. We report on the utility of PI in the design, conduct and dissemination of the HIDDen study, a national, multicentre clinical study based across three UK centres.

Methods
A retrospective review of PI within the HIDDen study was conducted using field notes taken by the lead author from interactions throughout their involvement as a lay representative on the study. Key members of the HIDDen study were interviewed and data analysed to explore adherence to the UK Standards.

Results
There was universal support for PI across the study management group with genuine inclusivity of lay members of the committee. All six of the UK Standards were met to varying degrees. The greatest opportunities lay in ‘working together’ and ‘support and learning’. There were challenges meeting ‘governance’ with evidence of participation in decision making but less evidence of opportunities in management, regulation, leadership.

Conclusion
This study concurs with previous research supporting the utility of the Standards in the conduct and evaluation of PI in clinical research. To our knowledge this is the first multi-national study to be evaluated against the UK Standards.
Fractal dimension analysis as an easy computational approach to improve breast cancer histopathological diagnosis
Authors: da Silva Lucas Glaucio , da Silva Monteiro Waleska Rayanne Sizinia , de Aguiar Moreira Tiago Medeiros , Rabelo Maria Aparecida Esteves , de Assis Emílio Augusto Campos Pereira , de Souza Gustavo Torres 
Published: April 2021

AbstractHistopathology is a well-established standard diagnosis employed for the majority of malignancies, including breast cancer. Nevertheless, despite training and standardization, it is considered operator-dependent and errors are still a concern. Fractal dimension analysis is a computational image processing technique that allows assessing the degree of complexity in patterns. We aimed here at providing a robust and easily attainable method for introducing computer-assisted techniques to histopathology laboratories. Slides from two databases were used: A) Breast Cancer Histopathological; and B) Grand Challenge on Breast Cancer Histology. Set A contained 2480 images from 24 patients with benign alterations, and 5429 images from 58 patients with breast cancer. Set B comprised 100 images of each type: normal tissue, benign alterations, in situ carcinoma, and invasive carcinoma. All images were analyzed with the FracLac algorithm in the ImageJ computational environment to yield the box count fractal dimension (Db) results. Images on set A on 40x magnification were statistically different (p = 0.0003), whereas images on 400x did not present differences in their means. On set B, the mean Db values presented promissing statistical differences when comparing. Normal and/or benign images to in situ and/or invasive carcinoma (all p < 0.0001). Interestingly, there was no difference when comparing normal tissue to benign alterations. These data corroborate with previous work in which fractal analysis allowed differentiating malignancies. Computer-aided diagnosis algorithms may beneficiate from using Db data; specific Db cut-off values may yield ~ 99% specificity in diagnosing breast cancer. Furthermore, the fact that it allows assessing tissue complexity, this tool may be used to understand the progression of the histological alterations in cancer.
Investigating prolonged social withdrawal behaviour as a risk factor for self-harm and suicidal behaviours
Authors: Zhu Shimin , Lee Paul H. , Wong Paul W. C. 
Published: April 2021

BackgroundSelf-harm and suicidal behaviour are recognised as public health concerns. Prolonged social withdrawal behaviour, orhikikomori, is reported as a risk factor for suicidal behaviour.AimsTo examine the occurrence and additional risk of prolonged social withdrawal behaviour on self-harm and suicidal behaviour among Chinese university students.MethodA cross-sectional online survey was conducted with three universities in southern China. A two-stage random sampling was adopted for recruitment, with students in different years of study, in different departments of each participating university. Hierarchical logistic regression analyses were conducted to investigate the sociodemographic and psychological correlates of self-harm and suicidal behaviours among male and female participants withhikikomoristatus.ResultsOf the students who completed the online survey, 1735 (72.23%) were included in the analysis; 11.5% (n= 200) reported self-harm behaviour and 11.8% (n= 204) reported suicidal behaviours in the past 12 months. Men showed a higher prevalence rate of self-harm than women (14.7%v.10.8%,P= 0.048), but a similar rate of suicidal behaviours (11.9%v.11.3%,P= 0.78). The overall prevalence rate of social withdrawal behaviour was 3.2% (7.0% for men and 2.3% for women,P< 0.001). Prolonged social withdrawal behaviour status was significantly associated with self-harm (odds ratio 2.00, 95% CI 1.22–3.29) and suicidal behaviour (odds ratio 2.35, 95% CI 1.45–3.81). However, the associations became statistically insignificant after adjustment for psychological factors in the final models in the logistic regression analyses.ConclusionsProlonged social withdrawal behaviour appears to be associated with self-harm and suicidal behaviour, but psychological factors have stronger links with suicidality.
Associations between hemispheric asymmetry and schizophrenia-related risk genes in people with schizophrenia and people at a genetic high risk of schizophrenia
Authors: Zhu Yue , Wang Shuai , Gong Xiaohong , Edmiston Elliot K. , Zhong Suyu , Li Chao , Zhao Pengfei , Wei Shengnan , Jiang Xiaowei , Qin Yue , Kang Jujiao , Wang Yi , Sun Qikun , Gong Gaolang , Wang Fei , Tang Yanqing 
Published: April 2021

BackgroundSchizophrenia is considered a polygenic disorder. People with schizophrenia and those with genetic high risk of schizophrenia (GHR) have presented with similar neurodevelopmental deficits in hemispheric asymmetry. The potential associations between neurodevelopmental abnormalities and schizophrenia-related risk genes in both schizophrenia and those with GHR remains unclear.AimsTo investigate the shared and specific alternations to the structural network in people with schizophrenia and those with GHR. And to identify an association between vulnerable structural network alternation and schizophrenia-related risk genes.MethodA total of 97 participants with schizophrenia, 79 participants with GHR and 192 healthy controls, underwent diffusion tensor imaging (DTI) scans at a single site. We used graph theory to characterise hemispheric and whole-brain structural network topological metrics. For 26 people in the schizophrenia group and 48 in the GHR group with DTI scans we also calculated their schizophrenia-related polygenic risk scores (SZ-PRSs). The correlations between alterations to the structural network and SZ-PRSs were calculated. Based on the identified genetic–neural association, bioinformatics enrichment was explored.ResultsThere were significant hemispheric asymmetric deficits of nodal efficiency, global and local efficiency in the schizophrenia and GHR groups. Hemispheric asymmetric deficit of local efficiency was significantly positively correlated with SZ-PRSs in the schizophrenia and GHR groups. Bioinformatics enrichment analysis showed that these risk genes may be linked to signal transduction, neural development and neuron structure. The schizophrenia group showed a significant decrease in the whole-brain structural network.ConclusionsThe shared asymmetric deficits in people with schizophrenia and those with GHR, and the association between anomalous asymmetry and SZ-PRSs suggested a vulnerability imaging marker regulated by schizophrenia-related risk genes. Our findings provide new insights into asymmetry regulated by risk genes and provides a better understanding of the genetic–neural pathological underpinnings of schizophrenia.
Screen, Notify, See, and Treat: Initial Results of Cervical Cancer Screening and Treatment in Rwanda
Authors: Muhimpundu Marie-Aimee , Ngabo Fidele , Sayinzoga Felix , Balinda Jean Paul , Rusine John , Harward Sardis , Eagan Arielle , Krivacsy Sara , Bayingana Alice , Uwimbabazi Jean Claude , Makuza Jean Damascene , Ngirabega Jean de Dieu , Binagwaho Agnes 
Published: April 2021

PURPOSE To describe the first year results of Rwanda's Screen, Notify, See, and Treat cervical cancer screening program, including challenges encountered and revisions made to improve service delivery. METHODS Through public radio broadcasts, meetings of local leaders, church networks, and local women's groups, public awareness of cervical cancer screening opportunities was increased and community health workers were enlisted to recruit and inform eligible women of the locations and dates on which services would be available. Screening was performed using human papillomavirus (HPV) DNA testing technology, followed by visual inspection with acetic acid (VIA), and cryotherapy, biopsy, and surgical treatment for those who tested HPV-positive. These services were provided by five district hospitals and 15 health centers to HIV-negative women of age 35-45 and HIV-positive women of age 30-50. Service utilization data were collected from the program's initiation in September 2013 to October 2014. RESULTS Of 7,520 cervical samples tested, 874 (11.6%) screened HPV-positive, leading 780 (89%) patients to undergo VIA. Cervical lesions were found in 204 patients (26.2%) during VIA; of these, 151 were treated with cryoablation and 15 were referred for biopsies. Eight patients underwent complete hysterectomy to treat advanced cervical cancer. Challenges to service delivery included recruitment of eligible patients, patient loss to follow-up, maintaining HIV status confidentiality, and efficient use of consumable resources. CONCLUSION Providing cervical cancer screening services through public health facilities is a feasible and valuable component of comprehensive women's health care in resource-limited settings. Special caution is warranted in ensuring proper adherence to follow-up and maintaining patient confidentiality.
Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation
Authors: Olson Amanda , Lin Ruitao , Marin David , Rafei Hind , Bdiwi Mustafa H. , Thall Peter F. , Basar Rafet , Abudayyeh Ala , Banerjee Pinaki , Aung Fleur M. , Kaur Indresh , Abueg Glorette , Rao Sheetal , Chemaly Roy , Mulanovich Victor , Al-Atrash Gheath , Alousi Amin M. , Andersson Borje S. , Anderlini Paolo , Bashir Qaiser , Castro Karla M. , Daher May , Galvan Isabel M. , Hosing Chitra , Im Jin S. , Jones Roy B. , Kebriaei Partow , Khouri Issa , Mehta Rohtesh , Molldrem Jeffrey , Nieto Yago , Oran Betul , Popat Uday , Qazilbash Muzaffar , Rondon Gabriela , Saini Neeraj , Spencer Bryan , Srour Samer , Washington Dominique , Barnett Melissa , Champlin Richard E. , Shpall Elizabeth J. , Rezvani Katayoun 
Published: April 2021

PURPOSE BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option. METHODS We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698 ) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed. RESULTS Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement. CONCLUSION Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT.
Association of Delirium during Critical Illness With Mortality: Multicenter Prospective Cohort Study
Authors: Hughes Christopher G. , Hayhurst Christina J. , Pandharipande Pratik P. , Shotwell Matthew S. , Feng Xiaoke , Wilson Jo Ellen , Brummel Nathan E. , Girard Timothy D. , Jackson James C. , Ely E. Wesley , Patel Mayur B. 
Published: April 2021

BACKGROUND:
The temporal association of delirium during critical illness with mortality is unclear, along with the associations of hypoactive and hyperactive motoric subtypes of delirium with mortality. We aimed to evaluate the relationship of delirium during critical illness, including hypoactive and hyperactive motoric subtypes, with mortality in the hospital and after discharge up to 1 year.

METHODS:
We analyzed a prospective cohort study of adults with respiratory failure and/or shock admitted to university, community, and Veterans Affairs hospitals. We assessed patients using the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the intensive care unit (ICU) and defined the motoric subtype according to the corresponding Richmond Agitation-Sedation Scale if delirium was present. We used Cox proportional hazard models, adjusted for baseline characteristics, coma, and daily hospital events, to determine whether delirium on a given day predicted mortality the following day in patients in the hospital and also to determine whether delirium presence and duration predicted mortality after discharge up to 1 year in patients who survived to hospital discharge. We performed similar analyses for hypoactive and hyperactive subtypes of delirium.

RESULTS:
Among 1040 critically ill patients, 214 (21%) died in the hospital and 204 (20%) died out-of-hospital by 1 year. Delirium was common, occurring in 740 (71%) patients for a median (interquartile range [IQR]) of 4 (2–7) days. Hypoactive delirium occurred in 733 (70%) patients, and hyperactive occurred in 185 (18%) patients, with a median (IQR) of 3 (2–7) days and 1 (1–2) days, respectively. Delirium on a given day (hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.32-6.21; P = .008), in particular the hypoactive subtype (HR, 3.35; 95% CI, 1.51-7.46; P = .003), was independently associated with an increased risk of death the following day in the hospital. Hyperactive delirium was not associated with an increased risk of death in the hospital (HR, 4.00; 95% CI, 0.49-32.51; P = .19). Among hospital survivors, neither delirium presence (HR, 1.01; 95% CI, 0.82-1.24; P = .95) nor duration (HR, 0.99; 95% CI, 0.97-1.01; P = .56), regardless of motoric subtype, was associated with mortality after hospital discharge up to 1 year.

CONCLUSIONS:
Delirium during critical illness is associated with nearly a 3-fold increased risk of death the following day for patients in the hospital but is not associated with mortality after hospital discharge. This finding appears primarily driven by the hypoactive motoric subtype. The independent relationship between delirium and mortality occurs early during critical illness but does not persist after hospital discharge.
Preparing Anesthesiology Residents for Operating Room Communication Challenges: A New Approach for Conflict Resolution Training
Authors: Birnbach David J. , Rosen Lisa F. , Fitzpatrick Maureen , Shekhter Ilya , Arheart Kristopher L. 
Published: April 2021

BACKGROUND:
The hierarchical culture in high-stake areas such as operating rooms (ORs) may create volatile communication challenges. This unfunded exploratory study sought to establish whether a conflict resolution course was effective in preparing anesthesiology residents to handle and deescalate disagreements that may arise in the clinical environment, especially when challenging a surgeon.

METHODS:
Thirty-seven anesthesiology residents were assessed for ability to deescalate conflict. Nineteen had completed a conflict resolution course, and 18 had not. The 2-hour course used 10 videotaped vignettes that showed attending anesthesiologists, patients, and surgeons challenging residents in a potentially confrontational situation. Guided review of the videos and discussions was focused on how the resident could optimally engage in conflict resolution. To determine efficacy of the conflict resolution course, we used simulation-based testing. The setting was a simulated OR with loud music playing (75–80 dB) under the control of the surgeon. The music was used as a tool to create a potential, realistic confrontation with the surgeon to test conflict resolution skills. The initial evaluation of the resident was whether they ignored the music, asked for the surgeon to turn it off, or attempted to turn it off themselves. The second evaluation was whether the resident attempted to deescalate (eg, calmly negotiate for the music to be turned off or down) when the surgeon was scripted to adamantly refuse. Two trained observers evaluated residents’ responses to the surgeon’s refusal.

RESULTS:
Of the residents who experienced the confrontational situation and had not yet taken the conflict resolution course, 1 of 5 (20.0%; 95% CI, 0.5–71.6) were judged to have deescalated the situation. In comparison, of those who had taken the course, 14 of 15 (93.3%; 95% CI, 68.1–99.8) were judged to have deescalated the situation (P = .002). Only 2 of 19 (10.5%; 95% CI, 1.3–33.1) of those who completed the course ignored the music on entering the OR versus 10 of 18 (55.6%; 95% CI, 30.8–78.5) who did not complete the course (P = .004).

CONCLUSIONS:
This study suggests that a conflict resolution course may improve the ability of anesthesiology residents to defuse clinical conflicts. It also demonstrated the effectiveness of a novel, simulation-based assessment of communication skills used to defuse OR confrontation.
The Evaluation of a Noninvasive Respiratory Volume Monitor in Mechanically Ventilated Neonates and Infants
Authors: Atkinson Douglas B. , Sens Brooke A. , Bernier Rachel S. , Gomez-Morad Andrea D. , Imsirovic Jasmin , Nasr Viviane G. 
Published: April 2021

BACKGROUND:
The respiratory volume monitor (RVM) (ExSpiron, Respiratory Motion Inc, Watertown, MA) uses thoracic impedance technology to noninvasively and continuously measure tidal volume (TV), respiratory rate (RR), and minute ventilation (MV). We aimed to validate the accuracy of the RVM to assess ventilation in neonates and infants by comparing it to spirometry.

METHODS:
We used the RVM and Respironics NM3 spirometer (Respironics NM3 Respiratory Profile Monitor, Philips Healthcare, Amsterdam, the Netherlands) to record simultaneous and continuous measurements of MV, TV, and RR. The RVM measurements, with and without external calibration, were compared to the Respironics NM3 spirometer using Bland-Altman analysis. The relative errors (Bland-Altman) between RVM and Respironics NM3 were calculated and used to compute individual patient bias, precision, and accuracy as the mean error, the standard deviation (SD) of the error, and the root mean square error. Bland-Altman limits of agreement (LoA) were computed, and equivalence tests were performed.

RESULTS:
Forty patients were studied to compare the RVM and Respironics NM3 measurements. The mean difference (ie, bias) for MV was 1.8% with 95% LoA, defined as mean ± 1.96 SD, in the range of −12.1% to 15.7%. Similarly, the mean difference (ie, bias) for TV and RR was 1.2% (95% LoA, −11.0% to 13.5%) and 0.6% (95% LoA, −3.7% to 5.0%), respectively. The mean measurement precision of the RVM relative to the Respironics NM3 for MV, TV, and RR was 10.8%, 8.9%, and 8.4%, respectively. The mean measurement accuracy for MV, TV, and RR across patients was 11.0%, 9.7%, and 7.1%, respectively.

CONCLUSIONS:
The data demonstrate that the RVM measures TV and MV in this cohort with an average relative error of 11% when using patient calibration and 16.9% without patient calibration. The average relative error of RR was 7.1%. The RVM provides accurate measurement of RR, TV, and MV in mechanically ventilated neonates and infants.