bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of tyrosine kinase inhibitors combined with antiprogrammed cell death protein 1 antibody in tyrosine kinase inhibitor-responsive patients with microsatellite stable/proficient mismatch repair metastatic colorectal adenocarcinoma: protocol for open-label, single-arm trial
Authors: Dong Qian , Diao Yanwen , Sun Xin , Zhou Yang , Ran Jialing , Zhang Jingdong 
Published: November 2022

Introduction
The prognosis of patients with advanced metastatic colorectal adenocarcinoma (mCRC) after multiple-line therapy remains poor due to the high tumour load, high level of malignancy and strong drug resistance. The application of programmed cell death protein 1 (PD-1) blockade alone for patients with microsatellite stable/proficient mismatch repair (MSS/pMMR) mCRC is ineffective. PD-1 blockade combined with antiangiogenic therapy has synergistic effects and has initially shown therapeutic effects. The aim of this trial is to explore the efficiency and safety of tyrosine kinase inhibitors (TKIs) combined with PD-1 blockade therapy in patients with mCRC with MSS/pMMR.

Methods and analysis
The screening phase of the trial will involve administering one cycle of TKIs (fruquintinib or regorafenib). Patients will be divided into three arms—arm A (obvious response to TKIs), arm B (general response to TKIs) and arm C (poor response to TKIs)—according to their response to TKIs, as determined by significant changes in imaging findings. Patients in arm A will then receive TKIs in combination with anti-PD-1 antibody, patients in arm C will withdraw from the study, and those in arm B will continue to take TKIs for another one further cycle. Next, patients with obvious response to TKIs will be reallocated to arm A, those with general response to TKIs will stay in arm B and will continue to take TKIs, and patients with poor response to TKIs will withdraw from the study. Administration of arm A or arm B will last until disease progression or intolerable toxicity. Anti-PD-1 antibody can be administered for up to 2 years. This trial will provide necessary data to improve the prognosis of patients with MSS/pMMR mCRC.

Trial registration number

NCT04483219; Pre-results.
COVID-19-related dynamic coagulation disturbances and anticoagulation strategies using conventional D-dimer and point-of-care Sonoclot tests: a prospective cohort study
Authors: Premkumar Madhumita , Loganathan Sekar , Kajal Kamal , Hazarika Amarjyoti , Soni Shiv , Puri Goverdhan Dutt , Sehgal Inderpaul Singh , Suri Vikas , Malhotra Pankaj , Singh Virendra , Duseja Ajay , Bhalla Ashish , Ahluwalia Jasmina , Kumar Narender , Kekan Kushal , Ram Sant , Singla Karan , Mahajan Varun , Yaddanapudi Narayana 
Published: November 2022

Objectives
Coagulation changes associated with COVID-19 suggest the presence of a hypercoagulable state with pulmonary microthrombosis and thromboembolic complications. We assessed the dynamic association of COVID-19-related coagulation abnormalities with respiratory failure and mortality.

Design
Single-centre, prospective cohort study with descriptive analysis and logistic regression.

Setting
Tertiary care hospital, North India.

Participants
Patients with COVID-19 pneumonia requiring intensive care unit (ICU) admission between August 2020 and November 2020.

Primary and secondary outcome measures
We compared the coagulation abnormalities using standard coagulation tests like prothrombin time, D-dimer, platelet count, etc and point-of-care global coagulation test, Sonoclot (glass beaded(gb) and heparinase-treated(h)). Incidence of thromboembolic or bleeding events and presence of endogenous heparinoids were assessed. Cox proportional Hazards test was used to assess the predictors of 28-day mortality.

Measurement
All patients underwent Sonoclot (glass beaded) test at admission apart from the routine investigations. In patients at risk of thromboembolic or bleeding phenomena, paired tests were performed at day 1 and 3 with Sonoclot. Activated clotting time (ACT) <110 s and peak amplitude >75 units were used as the cut-off for hypercoagulable state. Presence of heparin-like effect (HLE) was defined by a correction of ACT ≥40 s in h-Sonoclot.

Results
Of 215 patients admitted to ICU, we included 74 treatment naive subjects. A procoagulant profile was seen in 45.5% (n=5), 32.4% (n=11) and 20.7% (n=6) in low-flow, high-flow and invasive ventilation groups. Paired Sonoclot assays in a subgroup of 33 patients demonstrated the presence of HLE in 17 (51.5%) and 20 (62.5%) at day 1 and 3, respectively. HLE (day 1) was noted in 59% of those who bled during the disease course. Mortality was observed only in the invasive ventilation group (16, 55.2%) with overall mortality of 21.6%. HLE predicted the need for mechanical ventilation (HR 1.2 CI 1.04 to 1.4 p=0.00). On multivariate analysis, the presence of HLE (HR 1.01; CI 1.006 to 1.030; p=0.025), increased C reactive protein (HR 1.040; CI 1.020 to 1.090; p=0.014), decreased platelet function (HR 0.901; CI 0.702 to 1.100 p=0.045) predicted mortality at 28days.

Conclusion
HLE contributed to hypocoagulable effect and associated with the need for invasive ventilation and mortality in patients with severe COVID-19 pneumonia.

Trial registration

NCT04668404; ClinicalTrials.gov.in . Available fromhttps://clinicaltrials.gov/ct2/show/NCT04668404.
Associations between moral injury and ICD-11 post-traumatic stress disorder (PTSD) and complex PTSD among help-seeking nurses: a cross-sectional study
Authors: Jovarauskaite Lina , Murphy Dominic , Truskauskaite-Kuneviciene Inga , Dumarkaite Austeja , Andersson Gerhard , Kazlauskas Evaldas 
Published: November 2022

ObjectivesThis study aimed to evaluate how moral injury (MI), traumatic experiences and daily stressors were related to the symptoms of post-traumatic stress disorder (PTSD) and International Classification of Diseases 11th revision specific complex PTSD (CPTSD) symptoms of disturbances in self-organisation (DSO) in a treatment-seeking sample of nurses.DesignA cross-sectional study.SettingNurses from all regions of Lithuania participated in the study. The data were collected between April and May 2021.ParticipantsA total of 206 nurses, mean age 42.34 years (SD=11.68), 97.1% women and with 65% >10 years of work experience.ResultsThe prevalence of PTSD and CPTSD in the treatment-seeking sample of nurses was 9.2% and 10.2%, respectively. The results of structural equation modelling indicated an acceptable model fit for the model regarding the links between trauma exposure, daily stressors, MI, PTSD and DSO symptoms, (χ2 (df)=219.718 (123), p<0.001, Comparative Fit Index/Tucker-Lewis Index=0.937/0.922, root mean square error of approximation (90% CI)=0.062 (0.048 to 0.075), standardised root mean square residual=0.049). MI had a large effect on DSO symptoms, β=0.667, p<0.001, and a medium effect on PTSD symptoms, β=0.394, p<0.001. Daily stress but not trauma exposure was significantly related to MI, β=0.618, p<0.001.ConclusionsThe prevalence of PTSD and CPTSD in a treatment-seeking sample of nurses inform healthcare administrators, policymakers and medical staff about the demand for psychosocial interventions for healthcare workers focused on stress management to address their daily stressors and mitigate effects on MI or trauma-focused treatments for PTSD/CPTSD.Trial registration numberNCT04817995; Pre-results.
Comparative effectiveness of paediatric kidney stone surgery (the PKIDS trial): study protocol for a patient-centred pragmatic clinical trial
Authors: Ellison Jonathan S , Lorenzo Matthew , Beck Hunter , Beck Ruth , Chu David I , Forrest Christopher , Huang Jing , Kratchman Amy , Kurth Anna , Kurth Laura , Kurtz Michael , Lendvay Thomas , Sturm Renae , Tasian Gregory 
Published: November 2022

Introduction
The strength of the evidence base for the comparative effectiveness of three common surgical modalities for paediatric nephrolithiasis (ureteroscopy, shockwave lithotripsy and percutaneous nephrolithotomy) and its relevance to patients and caregivers are insufficient. We describe the methods and rationale for the Pediatric KIDney Stone (PKIDS) Care Improvement Network Trial with the aim to compare effectiveness of surgical modalities in paediatric nephrolithiasis based on stone clearance and lived patient experiences. This protocol serves as a patient-centred alternative to randomised controlled trials for interventions where clinical equipoise is lacking.

Methods and analysis
The PKIDS is a collaborative learning organisation composed of 26 hospitals that is conducting a prospective pragmatic clinical trial comparing the effectiveness of ureteroscopy, shockwave lithotripsy and percutaneous nephrolithotomy for youth aged 8–21 years with kidney and/or ureteral stones. Embedded within clinical care, the PKIDS trial will collect granular patient-level, surgeon-level and institution-level data, with a goal enrolment of 1290 participants over a 21-month period. The primary study outcome is stone clearance, defined as absence of a residual calculus of >4 mm on postoperative ultrasound. Secondary outcomes include patient-reported physical, emotional and social health outcomes (primarily using the Patient-Reported Outcome Measurement Information System), analgesic use and healthcare resource use. Timing and content of secondary outcomes assessments were set based on feedback from patient partners. Heterogeneity of treatment effect for stone clearance and patient-reported outcomes by participant and stone characteristics will be assessed.

Ethics and dissemination
This study is approved by the central institutional review board with reliance across participating sites. Participating stakeholders will review results and contribute to development dissemination at regional, national and international meetings.

Trial registration number

NCT04285658; Pre-results.
Protocol for a type 2 hybrid effectiveness-implementation study expanding, implementing and evaluating electronic health record-integrated patient-reported symptom monitoring in a multisite cancer centre
Authors: Garcia Sofia F , Smith Justin D , Kallen Michael , Webster Kimberly A , Lyleroehr Madison , Kircher Sheetal , Bass Michael , Cella David , Penedo Frank J 
Published: November 2022

Introduction
Cancer symptom monitoring and management interventions can address concerns that may otherwise go undertreated. However, such programmes and their evaluations remain largely limited to trials versus healthcare systemwide applications. We previously developed and piloted an electronic patient-reported symptom and need assessment (‘cPRO’ for cancer patient-reported outcomes) within the electronic health record (EHR). This study will expand cPRO implementation to medical oncology clinics across a large healthcare system. We will conduct a formal evaluation via a stepped wedge trial with a type 2 hybrid effectiveness-implementation design.

Methods and analysis
Aim 1 comprises a mixed method evaluation of cPRO implementation. Adult outpatients will complete cPRO assessments (pain, fatigue, physical function, depression, anxiety and supportive care needs) before medical oncology visits. Results are available in the EHR; severe symptoms and endorsed needs trigger clinician notifications. We will track implementation strategies using the Longitudinal Implementation Strategy Tracking System. Aim 2 will evaluate cPRO’s impact on patient and system outcomes over 12 months via (a) a quality improvement study (n=4000 cases) and (b) a human subjects substudy (n=1000 patients). Aim 2a will evaluate EHR-documented healthcare usage and patient satisfaction. In aim 2b, participating patients will complete patient-reported healthcare utilisation and quality, symptoms and health-related quality of life measures at baseline, 6 and 12 months. We will analyse data using generalised linear mixed models and estimate individual trajectories of patient-reported symptom scores at baseline, 6 and 12 months. Using growth mixture modelling, we will characterise the overall trajectories of each symptom. Aim 3 will identify cPRO implementation facilitators and barriers via mixed methods research gathering feedback from stakeholders. Patients (n=50) will participate in focus groups or interviews. Clinicians and administrators (n=40) will complete surveys to evaluate implementation. We will graphically depict longitudinal implementation survey results and code qualitative data using directed content analysis.

Ethics and dissemination
This study was approved by the Northwestern University Institutional Review Board (STU00207807). Findings will be disseminated via local and conference presentations and peer-reviewed journals.

Trial registration number

NCT04014751; ClinicalTrials.gov.
MET-PREVENT: metformin to improve physical performance in older people with sarcopenia and physical prefrailty/frailty – protocol for a double-blind, randomised controlled proof-of-concept trial
Authors: Rennie Katherine J , Witham Miles , Bradley Penny , Clegg Andrew , Connolly Stephen , Hancock Helen C , Hiu Shaun , Marsay Leanne , McDonald Claire , Robertson Laura , Simms Laura , Steel Alison J , Steves Claire J , Storey Bryony , Wason James , Wilson Nina , von Zglinicki Thomas , Sayer Avan A P 
Published: November 2022

IntroductionSkeletal muscle dysfunction is central to both sarcopenia and physical frailty, which are associated with a wide range of adverse outcomes including falls and fractures, longer hospital stays, dependency and the need for care. Resistance training may prevent and treat sarcopenia and physical frailty, but not everyone can or wants to exercise. Finding alternatives is critical to alleviate the burden of adverse outcomes associated with sarcopenia and physical frailty. This trial will provide proof-of-concept evidence as to whether metformin can improve physical performance in older people with sarcopenia and physical prefrailty or frailty.Methods and analysisMET-PREVENT is a parallel group, double-blind, placebo-controlled proof-of-concept trial. Trial participants can participate from their own homes, including completing informed consent and screening assessments. Eligible participants with low grip strength or prolonged sit-to-stand time together with slow walk speed will be randomised to either oral metformin hydrochloride 500 mg tablets or matched placebo, taken three times a day for 4 months. The recruitment target is 80 participants from two secondary care hospitals in Newcastle and Gateshead, UK. Local primary care practices will act as participant identification centres. Randomisation will be performed using a web-based minimisation system with a random element, balancing on sex and baseline walk speed. Participants will be followed up for 4 months post-randomisation, with outcomes collected at baseline and 4 months. The primary outcome measure is the four metre walk speed at the 4-month follow-up visit.Ethics and disseminationThe trial has been approved by the Liverpool NHS Research Ethics Committee (20/NW/0470), the Medicines and Healthcare Regulatory Authority (EudraCT 2020-004023-16) and the UK Health Research Authority (IRAS 275219). Results will be made available to participants, their families, patients with sarcopenia, the public, regional and national clinical teams, and the international scientific community.Trial registration numberNCT29932357.
Indocyanine green clearance test in liver transplantation: defining cut-off levels for graft viability assessment during organ retrieval and for the prediction of post-transplant graft function recovery - the Liver Indocyanine Green (LivInG) Trial Study Protocol
Authors: Coppola Alessandro , Bianco Giuseppe , Lai Quirino , Marrone Giuseppe , Caimano Miriam , Agnes Salvatore , Spoletini Gabriele 
Published: November 2022

Introduction
Viability assessment of the graft is essential to lower the risk of liver transplantation (LT) failure and need for emergency retransplantation, however, this still relies mainly on surgeon’s experience. Post-LT graft function recovery assessment is also essential to aid physicians in the management of LT recipients and guide them through challenging decision making.
This study aims to trial the use of indocyanine green clearance test (IGT) in the donor as an objective tool to assess graft viability and in the recipient to assess graft function recovery after LT.

Methods and analysis
This is an observational prospective single-centre study on consecutive liver transplant donors and recipients.

Primary objective
To determine the capability of IGT of predicting graft viability at the time of organ retrieval. Indocyanine green will be administered to the donor and the plasma disappearance rate (PDR) measured using the pulsidensitometric method. Some 162 IGT donor procedures will be required (α, 5%; β, 20%) using an IGT-PDR cut-off value of 13% to achieve a significant discrimination between viable and non-viable grafts.

Secondary objective
IGT-PDR will be measured at different time-points in the LT recipient: during the anhepatic phase, after graft reperfusion, at 24 hours, on day 3 and day 7 after LT. The slope of IGT values from the donor to the recipient will be evaluated for correlation with the development of early allograft dysfunction.

Ethics and dissemination
This research protocol was approved by Fondazione Policlinico Universitario Agostino Gemelli IRCCS Ethics Committee (reference number: 0048466/20, study ID: 3656) and by the Italian National Transplant Center (CNT) (reference number: Prot.11/CNT2021). Liver recipients will be required to provide written informed consent. Results will be published in international peer-reviewed scientific journals and presented in congresses.

Trial registration number

NCT05228587.
Physiotherapy exercise rehabilitation with tailored exercise adherence support for people with osteoporosis and vertebral fractures: protocol for a randomised controlled trial – the OsteoPorosis Tailored exercise adherence INtervention (OPTIN) study
Authors: Barker Karen L , Room Jonathan , Knight Ruth , Hannink Erin , Newman Meredith 
Published: November 2022

IntroductionVertebral fragility fractures affect at least 20% of the older population in the UK. Best practice guidelines recommend the use of exercise to slow the rate of bone loss, to maintain muscle strength and physical function, and to prevent falls and further fractures. However, treatment effects are often small and difficult to sustain and adherence, or the extent to which patients engage in treatment, has been identified as an important issue by many studies. Our hypothesis is that integrating adherence intervention strategies with an exercise intervention will be beneficial. We will compare physiotherapy exercise rehabilitation with adherence support versus physiotherapy exercise rehabilitation alone in terms of effects on (A) physical function, quality of life and fear of falling and (B) exercise self-efficacy and adherence.Methods and analysisA multicentre, two-arm, parallel group, superiority randomised controlled trial with blinded assessments at baseline (0) and 4, 8 and 12 months, with a nested qualitative study and health economic analysis. 116 participants will be allocated to either (1) outpatient physiotherapy which will include a musculoskeletal assessment and treatment including balance, posture, strength training and low impact weight-bearing exercises over 16 weeks or (2) OsteoPorosis Tailored exercise adherence INtervention intervention. This includes standard physiotherapy as above plus an additional, integrated assessment interview (30 min) and 60 min of adherence support spread over the subsequent 16 weeks.Ethics and disseminationThe study protocol was approved by West of Scotland Research Ethics Committee 4 (21/WS/0071). Trial registration numberNCT14465704. The paper is based on Protocol V.4.Trial registration numberNCT 14465704.
An explainable machine learning model for predicting the outcome of ischemic stroke after mechanical thrombectomy
Authors: Yao Zhelv , Mao Chenglu , Ke Zhihong , Xu Yun 
Published: November 2022

BackgroundThere is high variability in the clinical outcomes of patients with acute ischemic stroke (AIS) after mechanical thrombectomy (MT).Methods217 consecutive patients with anterior circulation large vessel occlusion who underwent MT between August 2018 and January 2022 were analysed. The primary outcome was functional independence defined as a modified Rankin Scale score of 0–2 at 3 months. In the derivation cohort (August 2018 to December 2020), 7 ensemble ML models were trained on 70% of patients and tested on the remaining 30%. The model’s performance was further validated on the temporal validation cohort (January 2021 to January 2022). The SHapley Additive exPlanations (SHAP) framework was applied to interpret the prediction model.ResultsDerivation analyses generated a 9-item score (PFCML-MT) comprising age, National Institutes of Health Stroke Scale score, collateral status, and postoperative laboratory indices (albumin-to-globulin ratio, estimated glomerular filtration rate, blood neutrophil count, C-reactive protein, albumin and serum glucose levels). The area under the curve was 0.87 for the test set and 0.84 for the temporal validation cohort. SHAP analysis further determined the thresholds for the top continuous features. This model has been translated into an online calculator that is freely available to the public (https://zhelvyao-123-60-sial5s.streamlitapp.com).ConclusionsUsing ML and readily available features, we developed an ML model that can potentially be used in clinical practice to generate real-time, accurate predictions of the outcome of patients with AIS treated with MT.
Effect of fiber properties and dispersion management on distortions associated with two subcarriers modulation of laser diode in radio over fiber systems
Authors: Mahmoud Alaa , Abd El-Salam Yasmin , Ahmed Moustafa , Mohamed Tarek 
Published: November 2022

AbstractWe present numerical modeling and simulation on the effects of standard single-mode fiber (SSMF) properties and different dispersion management approaches on the distortions of laser diode. These distortions are associated with the two-tone modulation of laser diode for use in radio over fiber systems. The fiber properties include attenuation and dispersion. The dispersion management approaches include the use of nonzero dispersion-shifted fiber (NZ-DSF), fiber Brag grating (FBG), and dispersion-compensating fiber (DCF). The laser is directly modulated with two analog frequencies of 25 and 25.1 GHz at different modulation depths (m). The modulated laser signals are then propagated through SSMF at different lengths (L). The investigated laser signal distortions include the 2nd harmonic distortion (HD2), and the 2nd and 3rd intermodulation distortions (IMD2 and IMD3, respectively). The results reveal that all laser distortions are exacerbated as the fiber length increases, which is mainly due to the chromatic dispersion, while fiber attenuation has no effect. The use of dispersion management approaches gives almost similar effects on the reduction of IMD3 whenL = 1 km, regardless of the value ofm. Up tom = 0.3, DCF is the most effective approach for reducing all distortions over the entire fiber length range, while NZ-DSF is the least. WhenL = 2 km, FBG is the most effective approach for reducing both IMD2 and HD2 whenm ≥ 0.4, whereas whenLis increased to 6 km, DCF is the most effective approach up tom = 0.5.Graphical abstractSimulation setup of RoF system for two-tone direct modulation of laser diode using different dispersion management approaches