bluuebunny/crossref_metadata_2025_split huggingface dataset:
Point-of-care ultrasound of the heart and lungs in patients with respiratory failure: a pragmatic randomized controlled multicenter trial
Authors: Riishede M. , Lassen A. T. , Baatrup G. , Pietersen P. I. , Jacobsen N. , Jeschke K. N. , Laursen C. B. 
Published: April 2021

Abstract
Background
Point-of-care ultrasound is a focus oriented tool for differentiating among cardiopulmonary diseases. Its value in the hands of emergency physicians, with various ultrasound experience, remains uncertain. We tested the hypothesis that, in emergency department patients with signs of respiratory failure, a point-of-care cardiopulmonary ultrasound along with standard clinical examination, performed by emergency physicians with various ultrasound experience would increase the proportion of patients with presumptive diagnoses in agreement with final diagnoses at four hours after admission compared to standard clinical examination alone.

Methods
In this prospective multicenter superiority trial in Danish emergency departments we randomly assigned patients presenting with acute signs of respiratory failure to intervention or control in a 1:1 ratio by block randomization. Patients received point-of-care cardiopulmonary ultrasound examination within four hours from admission. Ultrasound results were unblinded for the treating emergency physician in the intervention group. Final diagnoses and treatment were determined by blinded review of the medical record after the patients´ discharge.

Results
From October 9, 2015 to April 5, 2017, we randomized 218 patients and included 211 in the final analyses. At four hours we found; no change in the proportion of patients with presumptive diagnoses in agreement with final diagnoses; intervention 79·25% (95% CI 70·3–86·0), control 77·1% (95% CI 68·0–84·3), an increased proportion of appropriate treatment prescribed; intervention 79·3% (95% CI 70·3–86·0), control 65·7% (95% CI 56·0–74·3) and of patients who spent less than 1 day in hospital; intervention n = 42 (39·6%, 25·8 38·4), control n = 25 (23·8%, 16·5–33·0). No adverse events were reported.

Conclusions
Focused cardiopulmonary ultrasound added to standard clinical examination in patients with signs of respiratory failure had no impact on the diagnostic accuracy, but significantly increased the proportion of appropriate treatment prescribed and the proportion of patients who spent less than 1 day in hospital.

Trial registration
https://clinicaltrials.gov/, number NCT 02550184.
Benign breast disease and changes in mammographic breast density
Authors: Reimers Laura L. , Goldberg Mandy , Tehranifar Parisa , Michels Karin B. , Cohn Barbara A. , Flom Julie D. , Wei Ying , Cirillo Piera , Terry Mary Beth 
Published: April 2021

AbstractBackgroundMammographic breast density (MBD) and benign breast disease (BBD) are two of the strongest risk factors for breast cancer. Understanding trends in MBD by age and parity in women with BBD is essential to the clinical management and prevention of breast cancer.MethodsUsing data from the Early Determinants of Mammographic Density (EDMD) study, a prospective follow-up study of women born in 1959–1967, we evaluated MBD in 676 women. We used linear regression with generalized estimating equations to examine associations between self-reported BBD and MBD (percent density, dense area, and non-dense area), assessed through a computer-assisted method.ResultsA prior BBD diagnosis (median age at diagnosis 32 years) was reported by 18% of our cohort. The median time from BBD diagnosis to first available study mammogram was 9.4 years (range 1.1–27.6 years). Women with BBD had a 3.44% higher percent MBD (standard error (SE) = 1.56,p-value = 0.03) on their first available mammogram than women without BBD. Compared with parous women without BBD, nulliparous women with BBD and women with a BBD diagnosis prior to first birth had 7–8% higher percent MBD (β= 7.25, SE = 2.43,p-value< 0.01 and β = 7.84, SE = 2.98,p-value = 0.01, respectively), while there was no difference in MBD in women with a BBD diagnosis after the first birth (β= −0.22, SE = 2.40,p-value = 0.93).ConclusionWomen with self-reported BBD had higher mammographic breast density than women without BBD; the association was limited to women with BBD diagnosed before their first birth.
Polymorphism on human aromatase affects protein dynamics and substrate binding: spectroscopic evidence
Authors: Di Nardo Giovanna , Di Venere Almerinda , Zhang Chao , Nicolai Eleonora , Castrignanò Silvia , Di Paola Luisa , Gilardi Gianfranco , Mei Giampiero 
Published: April 2021

AbstractHuman aromatase is a member of the cytochrome P450 superfamily, involved in steroid hormones biosynthesis. In particular, it converts androgen into estrogens being therefore responsible for the correct sex steroids balance. Due to its capacity in producing estrogens it has also been considered as a promising target for breast cancer therapy. Two single-nucleotide polymorphisms (R264C and R264H) have been shown to alter aromatase activity and they have been associated to an increased or decreased risk for estrogen-dependent pathologies. Here, the effect of these mutations on the protein dynamics is investigated by UV/FTIR and time resolved fluorescence spectroscopy. H/D exchange rates were measured by FTIR for the three proteins in the ligand-free, substrate- and inhibitor-bound forms and the data indicate that the wild-type enzyme undergoes a conformational change leading to a more compact tertiary structure upon substrate or inhibitor binding. Indeed, the H/D exchange rates are decreased when a ligand is present. In the variants, the exchange rates in the ligand-free and –bound forms are similar, indicating that a structural change is lacking, despite the single amino acid substitution is located in the peripheral shell of the protein molecule. Moreover, the fluorescence lifetimes data show that the quenching effect on tryptophan-224 observed upon ligand binding in the wild-type, is absent in both variants. Since this residue is located in the catalytic pocket, these findings suggest that substrate entrance and/or retention in the active site is partially compromised in both mutants. A contact network analysis demonstrates that the protein structure is organized in two main clusters, whose connectivity is altered by ligand binding, especially in correspondence of helix-G, where the amino acid substitutions occur. Our findings demonstrate that SNPs resulting in mutations on aromatase surface modify the protein flexibility that is required for substrate binding and catalysis. The cluster analysis provides a rationale for such effect, suggesting helix G as a possible target for aromatase inhibition.
Evaluating the effectiveness and utility of a novel culturally-adapted telemonitoring system in improving the glycaemic control of Asians with type-2 diabetes mellitus: a mixed method study protocol
Authors: Goh Kuan Liang Shawn , Lee Cia Sin , Koh Choon Huat Gerald , Ling Ng Ling , Ang Seng Bin , Oh Christina , Lin Yongqing , Yuan Wei , Zheng Qishi Charles , Tan Ngiap Chuan 
Published: April 2021

Abstract
Background
Regular supervision of patients with type-2 diabetes mellitus (T2DM) by healthcare providers is essential to optimise their glycaemic control but is challenging to achieve in current care models. Telemonitoring is postulated to bridge this gap by leveraging on internet-of-things and mobile-health technology. This study aims to determine the effectiveness of a novel telemonitoring system (OPTIMUM) in improving the glycaemic control of patients with T2DM compared with standard of care alone.

Methods
This mixed-method study comprises an initial randomised controlled trial involving 330 Asian adults with T2DM, aged 26–65 years old with an HbA1c of 7.5–10%, with 115 in the intervention and control arms each. Those in the intervention arm will use standardised Bluetooth-enabled devices to transmit their capillary glucose, blood pressure and weight measurements to the OPTIMUM system. Primary care physicians and nurses will remotely supervise them according to an embedded management algorithm for 6 months, including tele-education via weekly videos over 8 weeks and asynchronous tele-consultation if abnormal or absent parameters are detected. Patients in both arms will be assessed at baseline, 6, 12 and 24 months post-recruitment. The primary outcome will be their HbA1c difference between both arms at baseline and 6 months. Blood pressure and weight control; quality of life, medication adherence, confidence in self-management, diabetic literacy and related distress and healthcare utilisation using validated questionnaires; and incident retinal, renal, cardiac and cerebrovascular complications will be compared between the two arms as secondary outcomes at stipulated time-points. Intervention arm patients will be interviewed using qualitative research methods to understand their experience, acceptance and perceived usefulness of the OPTIMUM system.

Discussion
Overall, this study seeks to evaluate the effectiveness of cultural-adapted telemonitoring system in improving glycaemic control of Asians with type-2 diabetes mellitus compared to standard of care. The results of this trial will better inform policy makers in adopting telemedicine for population health management.

Trial registration
ClinicalTrials.gov NCT04306770. Registered on March 13, 2020.
Does the guided online cognitive behavioral therapy for insomnia “i-Sleep youth” improve sleep of adolescents and young adults with insomnia after childhood cancer? (MICADO-study): study protocol of a randomized controlled trial
Authors: Peersmann Shosha H. M. , van Straten Annemieke , Kaspers Gertjan J. L. , Thano Adriana , van den Bergh Esther , Grootenhuis Martha A. , van Litsenburg Raphaële R. L. 
Published: April 2021

AbstractBackgroundAdolescents and young adults who had childhood cancer are at increased risk for insomnia, due to being critically ill during an important phase of their life for the development of good sleep habits. Insomnia is disabling and prevalent after childhood cancer (26–29%) and negatively impacts quality of life, fatigue, pain, and general functioning and is often associated with other (mental) health problems. Insomnia and a history of childhood cancer both increase the risk of adverse health outcomes, posing a double burden for adolescents who had childhood cancer. The first-line treatment for insomnia is cognitive behavioral therapy for insomnia (CBT-I). However, access to this type of care is often limited. The guided online CBT-I treatment “i-Sleep” has been developed to facilitate access via online care. i-Sleep is shown effective in adult (breast cancer) patients, but it is unknown if iCBT-I is effective in pediatric oncology.Methods/designWe developed a youth version of i-Sleep. Our aim is to evaluate its effectiveness in a national randomized-controlled clinical trial comparing iCBT-I to a waiting-list control condition at 3 and 6 months (n = 70). The intervention group will be also assessed at 12 months to see whether the post-test effects are maintained. Adolescents and young adults aged 12–30 years with insomnia, diagnosed with (childhood) cancer, currently at least 6 months since their last cancer treatment will be eligible. Outcomes include sleep efficiency (actigraphic), insomnia severity (self-report), sleep and circadian activity rhythm parameters, fatigue, health-related quality of life, perceived cognitive functioning, chronic distress, depressive and anxiety symptoms, and intervention acceptability.DiscussionInsomnia is prevalent in the pediatric oncology population posing a double health burden for adolescents and young adults who had childhood cancer. If guided iCBT-I is effective, guidelines for insomnia can be installed to treat insomnia and potentially improve quality of life and the health of adolescents and young adults who had childhood cancer.Trial registrationNL7220(NTR7419; Netherlands Trial register). Registered on 2 August 2018
Whole-genome sequencing of phenotypically distinct inflammatory breast cancers reveals similar genomic alterations to non-inflammatory breast cancers
Authors: Li Xiaotong , Kumar Sushant , Harmanci Arif , Li Shantao , Kitchen Robert R. , Zhang Yan , Wali Vikram B. , Reddy Sangeetha M. , Woodward Wendy A. , Reuben James M. , Rozowsky Joel , Hatzis Christos , Ueno Naoto T. , Krishnamurthy Savitri , Pusztai Lajos , Gerstein Mark 
Published: April 2021

Abstract
Background
Inflammatory breast cancer (IBC) has a highly invasive and metastatic phenotype. However, little is known about its genetic drivers. To address this, we report the largest cohort of whole-genome sequencing (WGS) of IBC cases.

Methods
We performed WGS of 20 IBC samples and paired normal blood DNA to identify genomic alterations. For comparison, we used 23 matched non-IBC samples from the Cancer Genome Atlas Program (TCGA). We also validated our findings using WGS data from the International Cancer Genome Consortium (ICGC) and the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We examined a wide selection of genomic features to search for differences between IBC and conventional breast cancer. These include (i) somatic and germline single-nucleotide variants (SNVs), in both coding and non-coding regions; (ii) the mutational signature and the clonal architecture derived from these SNVs; (iii) copy number and structural variants (CNVs and SVs); and (iv) non-human sequence in the tumors (i.e., exogenous sequences of bacterial origin).

Results
Overall, IBC has similar genomic characteristics to non-IBC, including specific alterations, overall mutational load and signature, and tumor heterogeneity. In particular, we observed similar mutation frequencies between IBC and non-IBC, for each gene and most cancer-related pathways. Moreover, we found no exogenous sequences of infectious agents specific to IBC samples. Even though we could not find any strongly statistically distinguishing genomic features between the two groups, we did find some suggestive differences in IBC: (i) The MAST2 gene was more frequently mutated (20% IBC vs. 0% non-IBC). (ii) The TGF β pathway was more frequently disrupted by germline SNVs (50% vs. 13%). (iii) Different copy number profiles were observed in several genomic regions harboring cancer genes. (iv) Complex SVs were more frequent. (v) The clonal architecture was simpler, suggesting more homogenous tumor-evolutionary lineages.

Conclusions
Whole-genome sequencing of IBC manifests a similar genomic architecture to non-IBC. We found no unique genomic alterations shared in just IBCs; however, subtle genomic differences were observed including germline alterations in TGFβ pathway genes and somatic mutations in the MAST2 kinase that could represent potential therapeutic targets.
Increased collateral flow by rescue femorofemoral bypass dissolved residual thrombus in implanted iliofemoral artery stents: a case report
Authors: Haraki Tatsuo , Kondo Taichi , Kamei Izaya , Tanabe Takahiro 
Published: April 2021

Abstract
Background
Failed aortofemoral and femoropopliteal bypass grafts in the lower extremity artery usually result in acute limb ischemia. Endovascular treatment and surgical revascularization have been reported for limb salvage.

Case presentation
A 72-year-old Japanese man was admitted with acute limb ischemia due to failed aortofemoral and femoropopliteal bypass grafts. Endovascular treatment with balloon angioplasty, thrombectomy, and stent implantation in the long chronic total occlusion from the right common iliac artery to the superficial femoral artery did not result in efficient flow due to thrombus transfer from a failed aortofemoral bypass graft. However, a rescue femorofemoral bypass (the left femoral to the right deep femoral artery) improved his symptoms, and implanted in-stent flow was gradually recovered. Lower extremity angiography performed 5 months later confirmed the patency of the iliofemoral in-stent flow. However, the femorofemoral bypass graft was unfortunately occluded due to the progression of left external iliac artery stenosis. The patency of the iliofemoral in-stent flow was confirmed at 1 year by ultrasonography.

Conclusions
Improvement of the deep femoral artery flow plays an important role in the treatment of acute limb ischemia due to failed aortofemoral and femoropopliteal bypass grafts. Thus, increased collateral circulation to the periphery through the deep femoral artery dissolved the remaining in-stent thrombus in the iliofemoral artery.
Sustained oxygenation improvement after first prone positioning is associated with liberation from mechanical ventilation and mortality in critically ill COVID-19 patients: a cohort study
Authors:   The ICU-RER COVID-19 Collaboration, Scaramuzzo Gaetano , Gamberini Lorenzo , Tonetti Tommaso , Zani Gianluca , Ottaviani Irene , Mazzoli Carlo Alberto , Capozzi Chiara , Giampalma Emanuela , Bacchi Reggiani Maria Letizia , Bertellini Elisabetta , Castelli Andrea , Cavalli Irene , Colombo Davide , Crimaldi Federico , Damiani Federica , Fusari Maurizio , Gamberini Emiliano , Gordini Giovanni , Laici Cristiana , Lanza Maria Concetta , Leo Mirco , Marudi Andrea , Nardi Giuseppe , Papa Raffaella , Potalivo Antonella , Russo Emanuele , Taddei Stefania , Consales Guglielmo , Cappellini Iacopo , Ranieri Vito Marco , Volta Carlo Alberto , Guerin Claude , Spadaro Savino 
Published: April 2021

Abstract
Background
Prone positioning (PP) has been used to improve oxygenation in patients affected by the SARS-CoV-2 disease (COVID-19). Several mechanisms, including lung recruitment and better lung ventilation/perfusion matching, make a relevant rational for using PP. However, not all patients maintain the oxygenation improvement after returning to supine position. Nevertheless, no evidence exists that a sustained oxygenation response after PP is associated to outcome in mechanically ventilated COVID-19 patients. We analyzed data from 191 patients affected by COVID-19-related acute respiratory distress syndrome undergoing PP for clinical reasons. Clinical history, severity scores and respiratory mechanics were analyzed. Patients were classified as responders (≥ median PaO2/FiO2 variation) or non-responders (< median PaO2/FiO2 variation) based on the PaO2/FiO2 percentage change between pre-proning and 1 to 3 h after re-supination in the first prone positioning session. Differences among the groups in physiological variables, complication rates and outcome were evaluated. A competing risk regression analysis was conducted to evaluate if PaO2/FiO2 response after the first pronation cycle was associated to liberation from mechanical ventilation.

Results
The median PaO2/FiO2 variation after the first PP cycle was 49 [19–100%] and no differences were found in demographics, comorbidities, ventilatory treatment and PaO2/FiO2 before PP between responders (96/191) and non-responders (95/191). Despite no differences in ICU length of stay, non-responders had a higher rate of tracheostomy (70.5% vs 47.9, P = 0.008) and mortality (53.7% vs 33.3%, P = 0.006), as compared to responders. Moreover, oxygenation response after the first PP was independently associated to liberation from mechanical ventilation at 28 days and was increasingly higher being higher the oxygenation response to PP.

Conclusions
Sustained oxygenation improvement after first PP session is independently associated to improved survival and reduced duration of mechanical ventilation in critically ill COVID-19 patients.
Joint UAV channel modeling and power control for 5G IoT networks
Authors: Fu Xiuhua , Ding Tian , Peng Rongqun , Liu Cong , Cheriet Mohamed 
Published: April 2021

AbstractThis paper studies the communication problem between UAVs and cellular base stations in a 5G IoT scenario where multiple UAVs work together. We are dedicated to the uplink channel modeling and the performance analysis of the uplink transmission. In the channel model, we consider the impact of 3D distance and multi-UAVs reflection on wireless signal propagation. The 3D distance is used to calculate the path loss, which can better reflect the actual path loss. The power control factor is used to adjust the UAV's uplink transmit power to compensate for different propagation path losses, so as to achieve precise power control. This paper proposes a binary exponential power control algorithm suitable for 5G networked UAV transmitters and presents the entire power control process including the open-loop phase and the closed-loop phase. The effects of power control factors on coverage probability, spectrum efficiency and energy efficiency under different 3D distances are simulated and analyzed. The results show that the optimal power control factor can be found from the point of view of energy efficiency.
A new upper bound for the largest growth rate of linear Rayleigh–Taylor instability
Authors: Dou Changsheng , Wang Jialiang , Wang Weiwei 
Published: April 2021

AbstractWe investigate the effect of (interface) surface tensor on the linear Rayleigh–Taylor (RT) instability in stratified incompressible viscous fluids. The existence of linear RT instability solutions with largest growth rate Λ is proved under the instability condition (i.e., the surface tension coefficientϑis less than a threshold$\vartheta _{\mathrm{c}}$ϑc) by the modified variational method of PDEs. Moreover, we find a new upper bound for Λ. In particular, we directly observe from the upper bound that Λ decreasingly converges to zero asϑgoes from zero to the threshold$\vartheta _{\mathrm{c}}$ϑc.
The performance of some machine learning approaches and a rich context model in student answer prediction
Authors: Lincke Alisa , Jansen Marc , Milrad Marcelo , Berge Elias 
Published: April 2021

AbstractWeb-based learning systems with adaptive capabilities to personalize content are becoming nowadays a trend in order to offer interactive learning materials to cope with a wide diversity of students attending online education. Learners’ interaction and study practice (quizzing, reading, exams) can be analyzed in order to get some insights into the student’s learning style, study schedule, knowledge, and performance. Quizzing might be used to help to create individualized/personalized spaced repetition algorithm in order to improve long-term retention of knowledge and provide efficient learning in online learning platforms. Current spaced repetition algorithms have pre-defined repetition rules and parameters that might not be a good fit for students’ different learning styles in online platforms. This study uses different machine learning models and a rich context model to analyze quizzing and reading records from e-learning platform called Hypocampus in order to get some insights into the relevant features to predict learning outcome (quiz answers). By knowing the answer correctness, a learning system might be able to recommend personalized repetitive schedule for questions with maximizing long-term memory retention. Study results show that question difficulty level and incorrectly answered previous questions are useful features to predict the correctness of student’s answer. The gradient-boosted tree and XGBoost models are best in predicting the correctness of the student’s answer before answering a quiz. Additionally, some non-linear relationship was found between the reading learning material behavior in the platform and quiz performance that brings added value to the accuracy for all used models.