bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QOL NL) in the Dutch population: a validation study
Authors: Keizer Alieke L , van Kesteren Paul J M , Terwee Caroline , de Lange Maria E , Hehenkamp Wouter J K , Kok Helen S 
Published: November 2021

ObjectiveUterine fibroids can cause a variety of symptoms in women, from heavy menstrual bleeding and dysmenorrhea to bulk symptoms. The Uterine Fibroid Symptom and health-related Quality Of Life questionnaire (UFS-QOL) is a patient-reported outcome measure developed for assessing fibroid-related symptoms in a standardised way. Our aim was to translate and validate the UFS-QOL in Dutch.DesignValidation study.SettingPatients were recruited by a gynaecologist at the outpatient clinic.ParticipantsWomen with uterine fibroids.MethodsThe UFS-QOL was translated into Dutch (UFS-QOL NL) and validated through testing construct validity (comprising of structural validity and hypotheses testing), reliability, responsiveness and interpretability, assessing floor and ceiling effects and minimal important change. An option to answer ‘not applicable’ was added to the translated questionnaire.Results191 women with uterine fibroids completed the UFS-QOL NL at baseline, after 2 weeks and after 3 months. The questionnaire retained the same factor structure after translation (Comparative Fit Index 0.94–0.95; Tucker-Lewis fit Index 0.93–0.95; Root Mean Square Error of Approximation 0.10–0.11) and correlations to other questionnaires (RAND 36, Hospital Anxiety and Depression Scale and Golombok Rust Inventory of Sexual Satisfaction) were generally moderate, as hypothesised (Pearson’s r 0.3–0.7). We found a sufficient reliability with intraclass correlation coefficients of approximately 0.8–0.9 for all subscales. Responsiveness was sufficient when testing hypotheses comparing women who had surgery with those who did not. Cronbach’s alpha was higher than 0.7 for all subscales, indicating sufficient internal consistency and there were no concerns about floor or ceiling effects. Minimal important change could not be calculated due to low correlation between the different subscales and the anchor question.ConclusionsThe results support the measurement properties of the Dutch UFS-QOL for assessing fibroid-related symptoms and health-related quality of life in Dutch women with uterine fibroids.
Protocol for a multicentre, parallel-group, open-label randomised controlled trial comparing ferric carboxymaltose with the standard of care in anaemic Malawian pregnant women: the REVAMP trial
Authors: Mwangi Martin N , Mzembe Glory , Moya Ernest , Braat Sabine , Harding Rebecca , Robberstad Bjarne , Simpson Julie , Stones William , Rogerson Stephen , Biselele Kabeya , Chinkhumba Jobiba , Larson Leila , Ataíde Ricardo , Phiri Kamija S , Pasricha Sant-Rayn 
Published: November 2021

IntroductionAnaemia in pregnancy remains a critical global health problem, affecting 46% of pregnant women in Africa and 49% in Asia. Oral iron therapy requires extended adherence to achieve correction of anaemia and replenishment of iron stores. Ferric carboxymaltose (FCM) is a recently established intravenous iron formulation associated with substantial advantages in safety, speed of delivery and total dose deliverable in a single infusion. We aim to determine whether FCM given once during the second trimester of pregnancy compared with standard oral iron distributed through routine antenatal services is effective and safe for treatment of moderate to severe maternal anaemia in sub-Saharan Africa.Methods and analysisThe randomized controlled trial of the effect of intravenous iron on anaemia in Malawian pregnant women (REVAMP) is a two-arm confirmatory individually randomised trial set in Blantyre and Zomba districts in Malawi. The trial will randomise 862 women in the second trimester of pregnancy with a capillary haemoglobin concentration below 100.0 g/L. The study comprises two arms: (a) intravenous FCM (20 mg/kg up to 1000 mg) given once at randomisation, and (b) standard of care oral iron (65 mg elemental iron two times per day) for 90 days (or the duration of pregnancy, whichever is shorter) provided according to local healthcare practices. Both arms receive sulfadoxine-pyrimethamine as intermittent preventive treatment in pregnancy. The primary outcome is the prevalence of anaemia (Hb <110.0 g/L) at 36 weeks’ gestation. Secondary outcomes include birth weight, gestation duration and safety outcomes, including clinical malaria, serious perinatal events and postpartum haematologic and health-related outcomes in the mother and child.Ethics and disseminationEthical approval was granted by the Research Ethics Committee (COMREC P.02/18/2357) in Malawi and the Human Research Ethics Committee (WEHI: 18/02), Melbourne, Australia. The protocol is registered with the Australian and New Zealand Clinical Trials Registry. The results will be shared with the local community that enabled the research, and also to the international fora.Trial registration numberACTRN12618001268235; Pre-results.
Feasibility of allied health assistant management of people with acute hip fracture: protocol for a feasibility randomised controlled trial
Authors: Snowdon David A , Vincent Peggy , Callisaya Michele L , Collyer Taya A , Wang Yi Tian , Taylor Nicholas F 
Published: November 2021

IntroductionGuidelines for hip fracture care state that patients with hip fracture should be mobilised on the day after surgery and at least once a day thereafter. However, compliance with these guidelines is poor. One approach that would assist physiotherapists to meet mobility guidelines after hip fracture is to delegate the provision of daily mobilisation to allied health assistants under their supervision. Therefore, we plan to conduct a randomised controlled trial to determine the feasibility of an allied health assistant providing daily inpatient rehabilitation to patients with hip fracture.Methods and analysisUsing a parallel group randomised controlled design with one-to-one allocation, participants will be randomly allocated to an experimental group (allied health assistant management) or a comparison group (physiotherapist management). Inclusion criteria are: adult with diagnosis of hip fracture; inpatient in acute hospital; walked independently pre-hip fracture and able to communicate in conversational English. The experimental group will receive routine physiotherapy rehabilitation, including daily mobilisation, from an allied health assistant following initial physiotherapist assessment. The comparison group will receive routine rehabilitation from a physiotherapist. The primary outcome will be the feasibility of allied health assistant management of patients with hip fracture. Feasibility will be determined using the following areas of focus in Bowen’s feasibility framework: acceptability (patient satisfaction), demand (proportion of patients who participate), implementation (time allied health assistant/physiotherapist spends with participant, occasions of service) and practicality (cost, adverse events). Staff involved in the implementation of allied health assistant care will be interviewed to explore their perspectives on feasibility. Secondary outcomes include compliance with daily mobilisation guidelines, discharge destination, hospital readmission, falls, functional activity and length of stay. We aim to recruit 50 participants. Descriptive statistics will be used to describe feasibility and mobilisation rates will be calculated using Cox proportional hazards regression to compare compliance with mobilisation guidelines.Ethics and disseminationEthics approval was obtained from the Peninsula Health human research ethics committee (HREC/63 005/PH-2020). The findings will be disseminated in peer-reviewed journals and conference presentations.Trail registration numberAustralian and New Zealand Clinical Trial Registry; ACTRN12620000877987; Pre-results.
MRI-based 3D retinal shape determination
Authors: van Vught Luc , Shamonin Denis P , Luyten Gregorius P M , Stoel Berend C , Beenakker Jan-Willem M 
Published: November 2021

ObjectiveTo establish a good method to determine the retinal shape from MRI using three-dimensional (3D) ellipsoids as well as evaluate its reproducibility.Methods and analysisThe left eyes of 31 volunteers were imaged using high-resolution ocular MRI. The 3D MR-images were segmented and ellipsoids were fitted to the resulting contours. The dependency of the resulting ellipsoid parameters on the evaluated fraction of the retinal contour was assessed by fitting ellipsoids to 41 different fractions. Furthermore, the reproducibility of the complete procedure was evaluated in four subjects. Finally, a comparison with conventional two-dimensional (2D) methods was made.ResultsThe mean distance between the fitted ellipsoids and the segmented retinal contour was 0.03±0.01 mm (mean±SD) for the central retina and 0.13±0.03 mm for the peripheral retina. For the central retina, the resulting ellipsoid radii were 12.9±0.9, 13.7±1.5 and 12.2±1.2 mm along the horizontal, vertical and central axes. For the peripheral retina, these radii decreased to 11.9±0.6, 11.6±0.4 and 10.4±0.7 mm, which was accompanied by a mean 1.8 mm posterior shift of the ellipsoid centre. The reproducibility of the ellipsoid fitting was 0.3±1.2 mm for the central retina and 0.0±0.1 mm for the peripheral retina. When 2D methods were used to fit the peripheral retina, the fitted radii differed a mean 0.1±0.1 mm from the 3D method.ConclusionAn accurate and reproducible determination of the 3D retinal shape based on MRI is provided together with 2D alternatives, enabling wider use of this method in the field of ophthalmology.
Time for change in practice of in-patient oxygen therapy: a period-limited, multidimensional approach to improve oxygen prescription compliance: quality improvement project at Hamad General Hospital, Qatar
Authors: Rose Samman , Sardar Sundus , Sasi Sreethish , Al Mohanadi Dabia Hamad S H , Al-Mohammed Ahmed Ali A A , Zahid Muhammad 
Published: November 2021

Prescription of oxygen therapy has traditionally poor compliance across the globe and mostly given to patients on verbal orders leading to under or overuse. The British Thoracic Society (BTS) guidelines (2017) recommend that oxygen therapy must be prescribed. Our study aimed to assess the prescription practice of oxygen therapy for patients admitted to acute medical assessment unit and general medical wards at Hamad General Hospital, Qatar and to achieve 80% compliance of valid oxygen therapy prescription implementing the quality improvement model against the BTS guidelines.The prescription practice of oxygen therapy was audited between April 2019 and August 2019. Using a Plan, Do, Study, Act (PDSA) model of improvement and multiple interventions was performed in the eight PDSA cycles, including (1) educational sessions for residents/fellows/nurses, (2) introduction of electronic prescription, (3) emails, posters/flyers, (4) nurse-led reminders and (5) re-enforced teaching for new residents. Data were then collected using a questionnaire assessing electronic prescriptions and documentation. Our baseline study regarding oxygen therapy showed limited awareness of BTS guidelines regarding the documentation of initiation and further adjustment of oxygen therapy. There was a lack of compliance with oxygen prescription; none of the patients had a valid prescription on our computer-based prescription (Cerner). The duration, target range and indications of Oxygen therapy were documented in 25% (18/72), 45.8% (33/72) and 42% (30/72) patients, respectively. Oxygen was initiated by communication order only. In a total of 16 weeks period, the repeated PDSA cycles showed significant improvement in safe oxygen prescription practices. Following intervention, oxygen electronic prescription, documentation of indications for oxygen therapy, target oxygen saturation and wean-off plan improved to 93%, 85%, 86 % and 80 %, respectively.We concluded that poor compliance to oxygen therapy Orders is a universal issue, which can be successfully managed using small-scale PDSA cycles to ensure sustained improvement through multidimensional interventions, continuous reinforcement and frequent reassessments.
Pan-cancer landscape ofCD274(PD-L1) rearrangements in 283,050 patient samples, its correlation with PD-L1 protein expression, and immunotherapy response
Authors: Kelly Andrew D , Murugesan Karthikeyan , Kuang Zheng , Montesion Meagan , Ross Jeffrey S , Albacker Lee A , Huang Richard S P , Lin Douglas I , Demirci Umut , Creeden James 
Published: November 2021

BackgroundImmune checkpoint inhibitors (ICIs) benefit patients with multiple cancer types, however, additional predictive biomarkers of response are needed.CD274(programmed cell death ligand-1, PD-L1) gene rearrangements are positively associated with PD-L1 expression and may confer benefit to ICI, thus a pan-cancer characterization of these alterations is needed.MethodsWe analyzed 283,050 patient samples across multiple tumor types that underwent comprehensive genomic profiling for activatingCD274rearrangements and other alterations. The DAKO 22C3 Tumor Proportion Scoring (TPS) method was used for PD-L1 immunohistochemistry (IHC) testing in a small subset with available data (n=55,423). A retrospective deidentified real-world clinico-genomic database (CGDB) was examined for ICI treatment outcomes. We also report a detailed case ofCD274-rearranged metastatic rectal adenocarcinoma.ResultsWe identified 145 samples with functional rearrangements inCD274. There were significant enrichments forPIK3CA,JAK2,PDCD1LG2,CREBBP, andPBRM1co-mutations (ORs=2.1, 16.7, 17.8, 3.6, and 3.4, respectively, p<0.01). Genomic human papillomavirus (HPV)-16, Epstein-Barr virus, and mismatch repair genes also co-occurred (OR=6.2, 8.4, and 4.3, respectively, p<0.05). Median tumor mutational burden (TMB) was higher compared withCD274wild-type samples (7.0 vs 3.5 mutations/Mb, p=1.7e-11), with disease-specific TMB enrichment in non-small cell lung, colorectal, unknown primary, and stomach cancers. PD-L1 IHC skewed toward positivity (N=39/43 samples with ≥1% positivity). Of eight patients from the CGDB, three remained on ICI treatment after 6 months. Separately, one patient with metastatic rectal adenocarcinoma experienced a pathologic complete response on chemoimmunotherapy.ConclusionsCD274gene rearrangements are associated with increased PD-L1 IHC scores, higher TMB, and potential clinical benefit in ICI-treated patients with cancer.
CHA2DS2-VASc score stratifies mortality risk in patients with and without atrial fibrillation
Authors: Harb Serge C , Wang Tom Kai Ming , Nemer David , Wu Yuping , Cho Leslie , Menon Venu , Wazni Osama , Cremer Paul C , Jaber Wael 
Published: November 2021

ObjectivesThe CHA2DS2-VASc score is the preferred risk model for anticoagulation decision-making in atrial fibrillation (AF) patients. Recent studies have found this score to have prognostic value in other cardiovascular diseases. We assessed the relationships between CHA2DS2-VASc score and long-term mortality in adults referred for stress testing,Methods165 184 consecutive patients from January 1991 to December 2014 from a prospective registry were studied, with CHA2DS2-VASc score calculated for all patients, and AF and anticoagulation status were recorded. The primary endpoint was all-cause mortality.ResultsIn this cohort, 12 450 (7.5%) patients had AF and mean CHA2DS2-VASc score was 2.2±1.2. There were 22 152 (18.4%) deaths during mean follow-up of 6.1±4.8 years. In multivariable analysis, CHA2DS2-VASc score, presence of AF and anticoagulation use, along with end-stage renal failure and smoking were all independently associated with mortality with HRs (95% CIs) of 1.23 (1.21 to 1.25), 1.18 (1.10 to 1.27) and 1.50 (1.40 to 1.60), respectively. Higher CHA2DS2-VASc score was incrementally associated with worse survival both in patients with and without AF (log-rank p<0.001). Anticoagulation use was associated with reduced survival in non-AF patients with alternative anticoagulation indications at all CHA2DS2-VASc score categories, and AF patients with lower CHA2DS2-VASc score 0–2, but was protective in AF patients with higher CHA2DS2-VASc score 4–9.ConclusionIncrementally higher CHA2DS2-VASc score, a simple clinical tool, is associated with mortality in patients regardless of presence of AF and anticoagulation status. Anticoagulation use was associated with worse survival in non-AF patients and AF patients with low CHA2DS2-VASc scores, but was protective in AF patients with high CHA2DS2-VASc scores.
Third-order optical nonlinearity of DSR13/THF solutions under CW He–Ne laser irradiation using Z-scan method
Authors: Abbas Bassam , Alshikh Khalil Mohammad 
Published: November 2021

The Z-scan technique was employed to explore the third-order nonlinear optical properties of disperse red 13 organic chromophore solutions in tetrahydrofuran. A continuous-wave He–Ne laser (632.8 nm) was used as a source of irradiation. The nonlinear absorption and nonlinear refractive index coefficients of this dye were investigated. The results showed that this dye has a good nonlinear response with its real and imaginary quantities of third-order susceptibility. The solutions showed negative nonlinear refraction. The best obtained value of the third-order susceptibility was 6.37 × 10–3 esu at a dye concentration of 3.15 × 10–4 mol/L. Moreover, the nonlinear optical properties were enhanced with higher dye concentrations, and an elevated trend in nonlinear absorption and nonlinear refractive index coefficients was observed. Also, it was found that the reverse saturable absorption was the main mechanism responsible for the two-photon absorption effect in DSR13/THF samples.
Plasticity in the Absence of NOTCH Uncovers a RUNX2-Dependent Pathway in Small Cell Lung Cancer
Authors: Hong Deli , Knelson Erik H. , Li Yixiang , Durmaz Yavuz T. , Gao Wenhua , Walton Emily , Vajdi Amir , Thai Tran , Sticco-Ivins Maura , Sabet Amin H. , Jones Kristen L. , Schinzel Anna C. , Bronson Rod T. , Nguyen Quang-De , Tolstorukov Michael Y. , Vivero Marina , Signoretti Sabina , Barbie David A. , Oser Matthew G. 
Published: November 2021

AbstractNeuroendocrine to nonneuroendocrine plasticity supports small cell lung cancer (SCLC) tumorigenesis and promotes immunogenicity. Approximately 20% to 25% of SCLCs harbor loss-of-function (LOF) NOTCH mutations. Previous studies demonstrated that NOTCH functions as a SCLC tumor suppressor, but can also drive nonneuroendocrine plasticity to support SCLC growth. Given the dual functionality of NOTCH, it is not understood why SCLCs select for LOF NOTCH mutations and how these mutations affect SCLC tumorigenesis. In a CRISPR-based genetically engineered mouse model of SCLC, genetic loss of Notch1 or Notch2 modestly accelerated SCLC tumorigenesis. Interestingly, Notch-mutant SCLCs still formed nonneuroendocrine subpopulations, and these Notch-independent, nonneuroendocrine subpopulations were driven by Runx2-mediated regulation of Rest. Notch2-mutant nonneuroendocrine cells highly express innate immune signaling genes including stimulator of interferon genes (STING) and were sensitive to STING agonists. This work identifies a Notch-independent mechanism to promote nonneuroendocrine plasticity and suggests that therapeutic approaches to activate STING could be selectively beneficial for SCLCs with NOTCH2 mutations.Significance:A genetically engineered mouse model of NOTCH-mutant SCLC reveals that nonneuroendocrine plasticity persists in the absence of NOTCH, driven by a RUNX2-REST–dependent pathway and innate immune signaling.
Sun Exposure Is Associated with Reduced Breast Cancer Risk among Women Living in the Caribbean: The Atabey Study in Puerto Rico
Authors: Nazario Cruz M. , Rosario-Rosado Rosa V. , Schelske-Santos Michelle , Mansilla-Rivera Imar , Ramírez-Marrero Farah A. , Nie Jing , Piovanetti-Fiol Paola , Hernández-Santiago Johan , Freudenheim Jo L. 
Published: November 2021

Abstract

Background:
Though inconsistent, there is evidence that sun exposure is associated with reduced breast cancer risk. Previous studies have been conducted in geographical regions with seasonal variation in UV radiation, including periods of low to no exposure, and among participants mostly of European descent. Puerto Rico has no significant seasonal fluctuation, with continuous exposure to very high UV radiation.

Methods:
We conducted a population-based case–control study of breast cancer among women in metropolitan San Juan, Puerto Rico, examining a cumulative sun exposure index (SEI) based on a comparison of reflectance of sun-exposed and non-exposed skin. A chromameter was used to measure skin reflectance and estimate the difference between constitutive (unexposed) and facultative (exposed) skin pigmentation in 307 cases and 328 controls. Breast cancer risk factors were ascertained with interviewer-administered questionnaires. OR and 95% confidence intervals (CI) were estimated with unconditional logistic regression.

Results:
Adjusted breast cancer odds were lower for the highest tertile of the SEI (ORadj = 0.47; 95% CI, 0.29–0.74). Results were similar within strata of estrogen receptor status. In analyses stratified by constitutive skin pigmentation, among participants with darker skin color, breast cancer risk was lower with more sun exposure (ORadj = 0.33; 95% CI, 0.16–0.70).

Conclusions:
We found lower risk of breast cancer associated with greater sun exposure in a population living with high, continuous sun exposure. This beneficial finding should be placed in the context of other effects of sun exposure.

Impact:
Sun exposure is a modifiable factor that may contribute, directly or indirectly, to lower breast cancer risk.
STimulator of INterferon Genes Agonism Accelerates Antitumor Activity in Poorly Immunogenic Tumors
Authors: Perera Samanthi A. , Kopinja Johnny E. , Ma Yanhong , Muise Eric S. , Laskey Jason , Chakravarthy Kalyan , Chen Yiping , Cui Long , Presland Jeremy , Sathe Manjiri , Javaid Sarah , Minnihan Ellen C. , Ferguson Heidi M. , Piesvaux Jennifer , Pan Bo-Sheng , Zhao Shuxia , Sharma Sharad K. , Woo Hyun Chong , Pucci Vincenzo , Knemeyer Ian , Cemerski Saso , Cumming Jared , Trotter B. Wesley , Tse Archie , Khilnani Anuradha , Ranganath Sheila , Long Brian J. , Bennett David Jonathan , Addona George H. 
Published: November 2021

Abstract
The innate immune agonist STING (STimulator of INterferon Genes) binds its natural ligand 2′3′-cGAMP (cyclic guanosine-adenosine monophosphate) and initiates type I IFN production. This promotes systemic antigen-specific CD8+ T-cell priming that eventually provides potent antitumor activity. To exploit this mechanism, we synthesized a novel STING agonist, MSA-1, that activates both mouse and human STING with higher in vitro potency than cGAMP. Following intratumoral administration of MSA-1 to a panel of syngeneic mouse tumors on immune-competent mice, cytokine upregulation and its exposure were detected in plasma, other tissues, injected tumors, and noninjected tumors. This was accompanied by effective antitumor activity. Mechanistic studies in immune-deficient mice suggested that antitumor activity of intratumorally dosed STING agonists is in part due to necrosis and/or innate immune responses such as TNF-α activity, but development of a robust adaptive antitumor immunity is necessary for complete tumor elimination. Combination with PD-1 blockade in anti–PD-1–resistant murine models showed that MSA-1 may synergize with checkpoint inhibitors but can also provide superior tumor control as a single agent. We show for the first time that potent cyclic dinucleotides can promote a rapid and stronger induction of the same genes eventually regulated by PD-1 blockade. This may have contributed to the relatively early tumor control observed with MSA-1. Taken together, these data strongly support the development of STING agonists as therapy for patients with aggressive tumors that are partially responsive or nonresponsive to single-agent anti–PD-1 treatment by enhancing the anti–PD-1 immune profile.