bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of a Viscous Liquid as an Aerosol for Post-Operative Adhesion Prevention: First Engineering Steps Towards Nozzle Design
Authors: Smith P. Alex , Keane Timothy J. , Serpelloni Stefano , Ramon Stephen G. , Taraballi Francesca 
Published: May 2021

Abstract
Postoperative adhesions are scar tissue that form between internal organs after surgery, leading to devastating life-long complications. Current adhesion barriers used clinically are solid sheets which can only be applied in open surgeries through large incisions. We have developed a material which can be applied as a liquid in minimally invasive surgeries which transitions into a solid thin film barrier upon contact with warm tissue. However, to be effective, it must be sprayed, and spraying a viscous liquid consistently is challenging. We proposed using a gas dispersant to facilitate aerosolization. In this study, we compared a commercially available nozzle without gas dispersant to a custom 3D printed nozzle with gas dispersant. For comparison, we measured both spray pattern and stiffness of the resulting gel. We found that when sprayed with gas dispersant, the spray pattern covered a larger area, and the resulting gel was stiffer than when sprayed without gas dispersant.
Modeling Reality: Revisiting Calvert’s Fitness Simulation
Authors: Hartzler Aniya , Qian Alice , Rupert Daniella , Sethi Maia , VanBibber Helina , Bova Taylor , Seshadri Dhruv , Drummond Colin 
Published: May 2021

Abstract
Wearable sensors have gained mainstream acceptance for health and fitness monitoring despite the absence of clinically validated analytic models for clinical decision support. Individual sensors measuring, say, EKG signal and heart rate can provide insight on cardiovascular response, but a more complete picture of health and fitness requires a more complete portfolio of sensors and data. This paper outlines the research underway to revisit and reconfigure the 1976 Calvert systems model of the effect of training on physical performance. Specifically, we use wearable sensor data from clinical trials to supplement a hybrid model created by nesting Perl’s Performance-Potential model within Calvert’s transfer function approach to system simulation. Contemporary simulation tools combined with wearables clinical trial data is the foundation for a more agile platform for simulation of fitness and exploration of causality between training and physical performance. This platform offers the opportunity to strategically integrate data from various wearable sensors in a fashion enabling improved support for post-injury and return to sport decision-making.
Natural Language Processing Based Machine Learning Model Using Cardiac MRI Reports to Identify Hypertrophic Cardiomyopathy Patients
Authors: Sundaram Divaakar Siva Baala , Arunachalam Shivaram P. , Damani Devanshi N. , Farahani Nasibeh Z. , Enayati Moein , Pasupathy Kalyan S. , Arruda-Olson Adelaide M. 
Published: May 2021

Abstract
Hypertrophic Cardiomyopathy (HCM) is the most common genetic heart disease in the US and is known to cause sudden death (SCD) in young adults. While significant advancements have been made in HCM diagnosis and management, there is a need to identify HCM cases from electronic health record (EHR) data to develop automated tools based on natural language processing guided machine learning (ML) models for accurate HCM case identification to improve management and reduce adverse outcomes of HCM patients.
Cardiac Magnetic Resonance (CMR) Imaging, plays a significant role in HCM diagnosis and risk stratification. CMR reports, generated by clinician annotation, offer rich data in the form of cardiac measurements as well as narratives describing interpretation and phenotypic description. The purpose of this study is to develop an NLP-based interpretable model utilizing impressions extracted from CMR reports to automatically identify HCM patients. CMR reports of patients with suspected HCM diagnosis between the years 1995 to 2019 were used in this study. Patients were classified into three categories of yes HCM, no HCM and, possible HCM. A random forest (RF) model was developed to predict the performance of both CMR measurements and impression features to identify HCM patients. The RF model yielded an accuracy of 86% (608 features) and 85% (30 features). These results offer promise for accurate identification of HCM patients using CMR reports from EHR for efficient clinical management transforming health care delivery for these patients.
Application of Machine Learning for Detection of Hypertrophic Cardiomyopathy Patients from Echocardiogram Measurements
Authors: Farahani Nasibeh Zanjirani , Enayati Moein , Sundaram Divaakar Siva Baala , Damani Devanshi , Kaggal Vinod C. , Zacher April L. , Geske Jeffrey B. , Kane Garvan , Arunachalam Shivaram Poigai , Pasupathy Kalyan , Arruda-Olson Adelaide M. 
Published: May 2021

Abstract
Hypertrophic cardiomyopathy (HCM) is a heritable, phenotypically diverse, and often asymptomatic heart muscle disease which is a major cause of sudden cardiac death (SCD) in young adults. The gold-standard for the diagnosis of HCM is echocardiography (echo), which is an ultrasound-based cardiac imaging modality. Across all sites of the Mayo Clinic enterprise, echo images and measurement data are reviewed, interpreted, and reported via the Echo Information Management System (EIMS). The objective of this paper is to develop a machine learning model for the identification of HCM from cardiac measurements obtained by the echo. We developed a novel machine learning model on patient demographic information and echo measurements that were retrieved from the EIMS digital data registry and selected by cardiologists.
Random forest (RF) was utilized to investigate the predictive performance of these features on the identification of HCM patients. The HCM cohort consists of 3,548 patients with at least one HCM diagnostic billing code (ICD-9 or ICD-10), from 2014 to 2019. The class labels “HCM yes” and “HCM no” were assigned by manual review of medical records as well as the outcomes of the gold standard imaging tests for HCM diagnosis. The developed model performed well in finding HCM patients with an accuracy of 95%, recall of 99%, and precision of 97%. The F1 score was 98 %, while 4% of patients were misclassified. This model will be translated into clinical practice for a clinical decision support system in EIMS to assist providers in the accurate diagnosis of HCM from echo data automatically while ensuring high-quality echo interpretation.
Measuring Line Pressure in Convection-Enhanced Delivery Infusions
Authors: Mehta Jason N. , Morales Brianna E. , Rylander Christopher G. 
Published: May 2021

Abstract
Convection-Enhanced Delivery (CED) is an investigative treatment for brain tumors. Reflux has been shown to be a key issue in the success of CED treatments. Minimal research has been conducted to determine the onset of reflux. Furthermore, the ability to identify reflux allows for corrective action to be taken before the consequences of reflux renders the treatment unsuccessful. Reflux could be quickly identified by changes in pressure measured in the catheter. In this study we examine the difficulties associated with measuring inline pressure. Results indicate the measured inline pressure will change depending on catheter length and orientation. Therefore, relative changes in pressure coupled with early treatment imaging could be utilized to determine the success of CED treatment.
Crisis Ventilator: A 3D Printed Option for Pressure Controlled Ventilation
Authors: Brito Alex , Fontaine Evan , El Haddi S. James , Chi MD FACS Albert 
Published: May 2021

Abstract
During the Coronavirus-19, or COVID-19, pandemic there was an early shortage of available ventilators. Domestic production was limited by dependence on overseas sources of raw materials despite partnering with automotive manufacturers. Our group has developed a 3D printed alternative called the CRISIS ventilator. Its design is similar to existing resuscitator devices on the market and uses a modified Pressure-Control ventilation. Here we compare the performance of the device on a simulated ARDS lung and handling of different clinical scenarios included tension pneumothorax and bronchospasm.
Testicular ischaemia: one of the most unknown of post-EVAR complications
Authors: Costa-Perez Laura , Arefai-Refai Bahaa , Ramirez-Montoya Mauricio , Hostench-Junoy Nuria 
Published: May 2021

Testicular ischaemia after endovascular aortic aneurysm repair (EVAR) is a very uncommon complication. There are only a few cases reported in the literature and the pathogenesis remains unclear. We report a case of unilateral testicular ischaemia in the early postoperative period after EVAR.A 78-year-old man underwent standard EVAR without immediate complications. Twenty-four hours after the procedure, the patient developed sudden onset of right scrotal pain and a low-grade fever. Urgent testicular ultrasound showed ischaemic signs compromising 75% of the testicle. The patient was successfully managed with conservative treatment.Although the pathogenesis is unknown, acute thrombosis of the testicle feeding arteries is postulated as the main hypothesis in the physiopathogenesis.
Sitagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with short bowel syndrome and colon in continuity: an open-label pilot study
Authors: Naimi Rahim Mohammad , Hvistendahl Mark Krogh , Thomassen Lise Margrete , Johnsen Hanna , Christiansen Charlotte Bayer , Holst Jens Juul , Hartmann Bolette , Jeppesen Palle Bekker 
Published: May 2021

ObjectivePatients with short bowel syndrome (SBS) and colon in continuity have better adaptation potential compared with patients with jejunostomy. Adaptation may involve enhanced postprandial secretion of the enteroendocrine hormones glucagon-like peptide (GLP)-1 and GLP-2 which are normally degraded by dipeptidyl peptidase (DPP)-4. Nevertheless, some patients with SBS with colon in continuity suffer from high-volume faecal excretions and have been shown to benefit from treatment with GLP-2. Therefore, we aimed to evaluate efficacy of sitagliptin, a DPP-4 inhibitor, on reducing faecal excretions in this patient group.DesignIn an open-label, case series, proof-of-concept pilot study, 100 mg oral sitagliptin was given two times per day for 8 weeks to patients with SBS with ≥50% colon in continuity with or without the need for parenteral support (PS). To assess intestinal function, metabolic balance studies were done at baseline and following 8 weeks of treatment.ResultsOf the 10 patients planned for enrolment, 8 patients were included; 7 patients completed the study. Although postprandial endogenous GLP-2 concentrations increased by 49 hours×pmol/L (39, 105; p=0.018) (median (min, max)), sitagliptin did not significantly reduce median faecal wet weight (−174 g/day (−1510, 675; p=0.176)) or increase intestinal wet weight absorption. However, heterogeneity in the treatment effect was observed: intestinal wet weight absorption increased in all four patients with intestinal failure. One patient achieved a reduction in PS by 500 mL per administration day.ConclusionFollowing this negative, small pilot study, larger, placebo-controlled, studies are needed to establish the therapeutic potential of DPP-4 inhibition in patients with SBS.
Assessing trauma care systems in low-income and middle-income countries: a systematic review and evidence synthesis mapping the Three Delays framework to injury health system assessments
Authors: Whitaker John , O'Donohoe Nollaig , Denning Max , Poenaru Dan , Guadagno Elena , Leather Andrew J M , Davies Justine I 
Published: May 2021

BackgroundThe large burden of injuries falls disproportionately on low/middle-income countries (LMICs). Health system interventions improve outcomes in high-income countries. Assessing LMIC trauma systems supports their improvement. Evaluating systems using a Three Delays framework, considering barriers to seeking (Delay 1), reaching (Delay 2) and receiving care (Delay 3), has aided maternal health gains. Rapid assessments allow timely appraisal within resource and logistically constrained settings. We systematically reviewed existing literature on the assessment of LMIC trauma systems, applying the Three Delays framework and rapid assessment principles.MethodsWe conducted a systematic review and narrative synthesis of articles assessing LMIC trauma systems. We searched seven databases and grey literature for studies and reports published until October 2018. Inclusion criteria were an injury care focus and assessment of at least one defined system aspect. We mapped each study to the Three Delays framework and judged its suitability for rapid assessment.ResultsOf 14 677 articles identified, 111 studies and 8 documents were included. Sub-Saharan Africa was the most commonly included region (44.1%). Delay 3, either alone or in combination, was most commonly assessed (79.3%) followed by Delay 2 (46.8%) and Delay 1 (10.8%). Facility assessment was the most common method of assessment (36.0%). Only 2.7% of studies assessed all Three Delays. We judged 62.6% of study methodologies potentially suitable for rapid assessment.ConclusionsWhole health system injury research is needed as facility capacity assessments dominate. Future studies should consider novel or combined methods to study Delays 1 and 2, alongside care processes and outcomes.
Health system influences on the implementation of tuberculosis infection prevention and control at health facilities in low-income and middle-income countries: a scoping review
Authors: Zwama Gimenne , Diaconu Karin , Voce Anna S , O'May Fiona , Grant Alison D , Kielmann Karina 
Published: May 2021

BackgroundTuberculosis infection prevention and control (TB-IPC) measures are consistently reported to be poorly implemented globally. TB-IPC guidelines provide limited recognition of the complexities of implementing TB-IPC within routine health systems, particularly those facing substantive resource constraints. This scoping review maps documented system influences on TB-IPC implementation in health facilities of low/middle-income countries (LMICs).MethodsWe conducted a systematic search of empirical research published before July 2018 and included studies reporting TB-IPC implementation at health facility level in LMICs. Bibliometric data and narratives describing health system influences on TB-IPC implementation were extracted following established methodological frameworks for conducting scoping reviews. A best-fit framework synthesis was applied in which extracted data were deductively coded against an existing health policy and systems research framework, distinguishing between social and political context, policy decisions, and system hardware (eg, information systems, human resources, service infrastructure) and software (ideas and interests, relationships and power, values and norms).ResultsOf 1156 unique search results, we retained 77 studies; two-thirds were conducted in sub-Saharan Africa, with more than half located in South Africa. Notable sociopolitical and policy influences impacting on TB-IPC implementation include stigma against TB and the availability of facility-specific TB-IPC policies, respectively. Hardware influences on TB-IPC implementation referred to availability, knowledge and educational development of staff, timeliness of service delivery, availability of equipment, such as respirators and masks, space for patient separation, funding, and TB-IPC information, education and communication materials and tools. Commonly reported health system software influences were workplace values and established practices, staff agency, TB risk perceptions and fears as well as staff attitudes towards TB-IPC.ConclusionTB-IPC is critically dependent on health system factors. This review identified the health system factors and health system research gaps that can be considered in a whole system approach to strengthen TB-IPC practices at facility levels in LMICs.
Ability of prehospital NEWS to predict 1-day and 7-day mortality is reduced in older adult patients
Authors: Pirneskoski Jussi , Lääperi Mitja , Kuisma Markku , Olkkola Klaus T , Nurmi Jouni 
Published: May 2021

BackgroundNational Early Warning Score (NEWS) does not include age as a parameter despite age is a significant independent risk factor of death. The aim of this study was to examine whether age has an effect on predictive performance of short-term mortality of NEWS in a prehospital setting. We also evaluated whether adding age as an additional parameter to NEWS improved its short-term mortality prediction.MethodsWe calculated NEWS scores from retrospective prehospital electronic patient record data for patients 18 years or older with sufficient prehospital data to calculate NEWS. We used area under receiver operating characteristic (AUROC) to analyse the predictive performance of NEWS for 1 and 7 day mortalities with increasing age in three different age groups: <65 years, 65–79 years and ≥80 years. We also explored the ORs for mortality of different NEWS parameters in these age groups. We added age to NEWS as an additional parameter and evaluated its effect on predictive performance.ResultsWe analysed data from 35 800 ambulance calls. Predictive performance for 7-day mortality of NEWS decreased with increasing age: AUROC (95% CI) for 1-day mortality was 0.876 (0.848 to 0.904), 0.824 (0.794 to 0.854) and 0.820 (0.788 to 0.852) for first, second and third age groups, respectively. AUROC for 7-day mortality had a similar trend. Addition of age as an additional parameter to NEWS improved its ability to predict short-term mortality when assessed with continuous Net Reclassification Improvement.ConclusionsAge should be considered as an additional parameter to NEWS, as it improved its performance in predicting short-term mortality in this prehospital cohort.
Nicotine-Induced ILF2 Facilitates Nuclear mRNA Export of Pluripotency Factors to Promote Stemness and Chemoresistance in Human Esophageal Cancer
Authors: Li Yue , Wang Meng , Yang Muwen , Xiao Yunyun , Jian Yunting , Shi Dongni , Chen Xiangfu , Ouyang Ying , Kong Lingzhi , Huang Xinjian , Bai Jiewen , Hu Yameng , Lin Chuyong , Song Libing 
Published: May 2021

Abstract

Balancing mRNA nuclear export kinetics with its nuclear decay is critical for mRNA homeostasis control. How this equilibrium is aberrantly disrupted in esophageal cancer to acquire cancer stem cell properties remains unclear. Here we find that the RNA-binding protein interleukin enhancer binding factor 2 (ILF2) is robustly upregulated by nicotine, a major chemical component of tobacco smoke, via activation of JAK2/STAT3 signaling and significantly correlates with poor prognosis in heavy-smoking patients with esophageal cancer. ILF2 bound the THO complex protein THOC4 as a regulatory cofactor to induce selective interactions with pluripotency transcription factor mRNAs to promote their assembly into export-competent messenger ribonucleoprotein complexes. ILF2 facilitated nuclear mRNA export and inhibited hMTR4-mediated exosomal degradation to promote stabilization and expression of SOX2, NANOG, and SALL4, resulting in enhanced stemness and tumor-initiating capacity of esophageal cancer cells. Importantly, inducible depletion of ILF2 significantly increased the therapeutic efficiency of cisplatin and abrogated nicotine-induced chemoresistance in vitro and in vivo. These findings reveal a novel role of ILF2 in nuclear mRNA export and maintenance of cancer stem cells and open new avenues to overcome smoking-mediated chemoresistance in esophageal cancer.

Significance:
This study defines a previously uncharacterized role of nicotine-regulated ILF2 in facilitating nuclear mRNA export to promote cancer stemness, suggesting a potential therapeutic strategy against nicotine-induced chemoresistance in esophageal cancer.
Phase I Study of Ceralasertib (AZD6738), a Novel DNA Damage Repair Agent, in Combination with Weekly Paclitaxel in Refractory Cancer
Authors: Kim Seung Tae , Smith Simon A. , Mortimer Peter , Loembé Arsene-Bienvenu , Cho Heejin , Kim Kyoung-Mee , Smith Claire , Willis Sophie , Irurzun-Arana Itziar , Berges Alienor , Hong Jung Yong , Park Se Hoon , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Kang Won Ki , Kozarewa Iwanka , Pierce Andrew J. , Dean Emma , Lee Jeeyun 
Published: May 2021

Abstract

Purpose:
Ceralasertib is a potent and selective oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related (ATR) protein.

Patients and Methods:
Eligible patients with solid tumors, enriched for melanoma, received ceralasertib in combination with a fixed dose of paclitaxel (80 mg/m2 on D1, D8, D15) in 28-day cycles. The dose of ceralasertib was escalated to reach an MTD in a rolling 6 design. The starting dose of ceralasertib was 40 mg QD. Fifty-seven patients (33 patients with melanoma who failed prior PD1/L1 treatment) were enrolled in 7 dose cohorts ranging from 40 mg QD to 240 mg BD plus weekly paclitaxel.

Results:
The RP2D was established as ceralasertib 240 mg BD days 1–14 plus paclitaxel 80 mg/m2 on D1, D8, D15 every 28 days. The most common toxicities were neutropenia (n = 39, 68%), anemia (n = 25, 44%), and thrombocytopenia (n = 21, 37%). In the full analysis set of 57 patients, the overall response rate (ORR) was 22.6% (95% CI, 12.5–35.3). In 33 patients with melanoma, resistant to prior anti-PD1 therapy, the ORR was 33.3% (95% CI, 18.0–51.8). In the melanoma subset, the mPFS was 3.6 months (95% CI, 2.0–5.8), the median duration of response was 9.9 months (95% CI, 3.7–23.2), and the mOS was 7.4 months (95% CI, 5.7–11.9).

Conclusions:
Ceralasertib in combination with paclitaxel was well tolerated in patients with advanced malignancies and showed evidence of antitumor activity. Durable responses were observed in patients with advanced cutaneous, acral, and mucosal melanoma resistant to anti-PD1/L1 treatment.
See related commentary by Ashworth, p. 4667
PML/RARα Destabilization by Hyperthermia: A New Model for Oncogenic Fusion Protein Degradation?
Authors: Wu Hsin Chieh , Rérolle Domitille , de Thé Hugues 
Published: May 2021

Abstract
Summary: In this issue, Maimaitiyiming and colleagues demonstrate thermic stress–induced PML/RARα oncogenic fusion protein destabilization driven by corepressor aggregation. Hyperthermia synergizes with PML/RARα degradation by arsenic trioxide (ATO) and may circumvent ATO-resistance in historic acute promyelocytic leukemia patients. This novel approach could be extended to other corepressor-associated oncogenic fusion proteins.
See related article by Maimaitiyiming et al., p. 388.