bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation and Clinical Adoption of Precision Oncology Workflows Across a Healthcare Network
Authors: Dias-Santagata Dora , Heist Rebecca S , Bard Adam Z , da Silva Annacarolina F L , Dagogo-Jack Ibiayi , Nardi Valentina , Ritterhouse Lauren L , Spring Laura M , Jessop Nicholas , Farahani Alexander A , Mino-Kenudson Mari , Allen Jill , Goyal Lipika , Parikh Aparna , Misdraji Joseph , Shankar Ganesh , Jordan Justin T , Martinez-Lage Maria , Frosch Matthew , Graubert Timothy , Fathi Amir T , Hobbs Gabriela S , Hasserjian Robert P , Raje Noopur , Abramson Jeremy , Schwartz Joel H , Sullivan Ryan J , Miller David , Hoang Mai P , Isakoff Steven , Ly Amy , Bouberhan Sara , Watkins Jaclyn , Oliva Esther , Wirth Lori , Sadow Peter M , Faquin William , Cote Gregory M , Hung Yin P , Gao Xin , Wu Chin-Lee , Garg Salil , Rivera Miguel , Le Long P , John Iafrate A , Juric Dejan , Hochberg Ephraim P , Clark Jeffrey , Bardia Aditya , Lennerz Jochen K 
Published: July 2022

AbstractBackgroundPrecision oncology relies on molecular diagnostics, and the value-proposition of modern healthcare networks promises a higher standard of care across partner sites. We present the results of a clinical pilot to standardize precision oncology workflows.MethodsWorkflows are defined as the development, roll-out, and updating of disease-specific molecular order sets. We tracked the timeline, composition, and effort of consensus meetings to define the combination of molecular tests. To assess clinical impact, we examined order set adoption over a two-year period (before and after roll-out) across all gastrointestinal and hepatopancreatobiliary (GI) malignancies, and by provider location within the network.ResultsDevelopment of 12 disease center-specific order sets took ~9 months, and the average number of tests per indication changed from 2.9 to 2.8 (P = .74). After roll-out, we identified significant increases in requests for GI patients (17%; P &lt; .001), compliance with testing recommendations (9%; P &lt; .001), and the fraction of “abnormal” results (6%; P &lt; .001). Of 1088 GI patients, only 3 received targeted agents based on findings derived from non-recommended orders (1 before and 2 after roll-out); indicating that our practice did not negatively affect patient treatments. Preliminary analysis showed 99% compliance by providers in network sites, confirming the adoption of the order sets across the network.ConclusionOur study details the effort of establishing precision oncology workflows, the adoption pattern, and the absence of harm from the reduction of non-recommended orders. Establishing a modifiable communication tool for molecular testing is an essential component to optimize patient care via precision oncology.
MHC Class I Enables MSCs to Evade NK-Cell–Mediated Cytotoxicity and Exert Immunosuppressive Activity
Authors: Oh Joo Youn , Kim Hyemee , Lee Hyun Ju , Lee Kangin , Barreda Heather , Kim Hyeon Ji , Shin Eunji , Bae Eun-Hye , Kaur Gagandeep , Zhang Yu , Kim Eunjae , Lee Jae young , Lee Ryang Hwa 
Published: July 2022

Abstract
Allogeneic mesenchymal stem/stromal cells (MSCs) are frequently used in clinical trials due to their low expression of major histocompatibility complex (MHC) class I and lack of MHC class II. However, the levels of MHC classes I and II in MSCs are increased by inflammatory stimuli, raising concerns over potential adverse effects associated with allogeneic cell therapy. Also, it is unclear how the host immune response to MHC-mismatched MSCs affects the therapeutic efficacy of the cells. Herein, using strategies to manipulate MHC genes in human bone marrow-derived MSCs via the CRISPR-Cas9 system, plasmids, or siRNAs, we found that inhibition of MHC class I—not MHC class II—in MSCs lowered the survival rate of MSCs and their immunosuppressive potency in mice with experimental autoimmune uveoretinitis, specifically by increasing MSC vulnerability to natural killer (NK)-cell-mediated cytotoxicity. A subsequent survey of MSC batches derived from 6 human donors confirmed a significant correlation between MSC survival rate and susceptibility to NK cells with the potency of MSCs to increase MHC class I level upon stimulation. Our overall results demonstrate that MHC class I enables MSCs to evade NK-cell-mediated cytotoxicity and exert immunosuppressive activity.
Biomechanical Assessment of Fracture Loads and Patterns of the Odontoid Process
Authors: Benca Emir , Zderic Ivan , van Knegsel Kenneth P. , Caspar Jan , Hirtler Lena , Fuchssteiner Christoph , Strassl Andreas , Gueorguiev Boyko , Widhalm Harald , Windhager Reinhard , Varga Peter 
Published: July 2022

Study Design.
Laboratory study.

Objective.
This study aimed to investigate the biomechanical competence and fracture characteristics of the odontoid process.

Summary of Background Data.
Odontoid fractures of the second cervical vertebra (C2) represent the most common spine fracture type in the elderly. However, very little is known about the underlying biomechanical fracture mechanisms.

Materials and Methods.
A total of 42 C2 human anatomic specimens were scanned via computed tomography, divided in six groups, and subjected to combined quasistatic loading at −15°, 0°, and 15° in sagittal plane and −50° and 0° in transverse plane until fracturing. Bone mineral density (BMD), height, fusion state of the ossification centers, stiffness, yield load, and ultimate load were assessed.

Results.
While lowest values for stiffness, yield load, and ultimate load were observed at load inclination of 15° in sagittal plane, no statistically significant differences were observed between the study groups (P≥0.235). BMD correlated positively with yield load (r
2=0.350, P<0.001) and ultimate load (r
2=0.955, P<0.001) but not with stiffness (r
2=0.082, P=0.07). The specimens with clearly distinguishable fusion of the ossification centers revealed less data scattering of the biomechanical outcomes.

Conclusion.
Load direction plays a subordinate role in traumatic fractures of the odontoid process. BMD was associated with significant correlation to the biomechanical outcomes. Thus, odontoid fractures appear to result from of an interaction between the load magnitude and bone quality.
Machine learning-based prediction of massive perioperative allogeneic blood transfusion in cardiac surgery
Authors: Tschoellitsch Thomas , Böck Carl , Mahečić Tina Tomić , Hofmann Axel , Meier Jens 
Published: July 2022

BACKGROUND
Massive perioperative allogeneic blood transfusion, that is, perioperative transfusion of more than 10 units of packed red blood cells (pRBC), is one of the main contributors to perioperative morbidity and mortality in cardiac surgery. Prediction of perioperative blood transfusion might enable preemptive treatment strategies to reduce risk and improve patient outcomes while reducing resource utilisation. We, therefore, investigated the precision of five different machine learning algorithms to predict the occurrence of massive perioperative allogeneic blood transfusion in cardiac surgery at our centre.

OBJECTIVE
Is it possible to predict massive perioperative allogeneic blood transfusion using machine learning?

DESIGN
Retrospective, observational study.

SETTING
Single adult cardiac surgery centre in Austria between 01 January 2010 and 31 December 2019.

PATIENTS
Patients undergoing cardiac surgery.

MAIN OUTCOME MEASURES
Primary outcome measures were the number of patients receiving at least 10 units pRBC, the area under the curve for the receiver operating characteristics curve, the F1 score, and the negative-predictive (NPV) and positive-predictive values (PPV) of the five machine learning algorithms used to predict massive perioperative allogeneic blood transfusion.

RESULTS
A total of 3782 (1124 female:) patients were enrolled and 139 received at least 10 pRBC units. Using all features available at hospital admission, massive perioperative allogeneic blood transfusion could be excluded rather accurately. The best area under the curve was achieved by Random Forests: 0.810 (0.76 to 0.86) with high NPV of 0.99). This was still true using only the eight most important features [area under the curve 0.800 (0.75 to 0.85)].

CONCLUSION
Machine learning models may provide clinical decision support as to which patients to focus on for perioperative preventive treatment in order to preemptively reduce massive perioperative allogeneic blood transfusion by predicting, which patients are not at risk.

TRIAL REGISTRATION
Johannes Kepler University Ethics Committee Study Number 1091/2021, Clinicaltrials.gov identifier NCT04856618.
The Prephase Nursing in Levodopa Carbidopa Intestinal Gel Therapy
Authors: Lezzi Pierluigi , Lupo Roberto , Lezzi Tania , Vitale Elsa 
Published: July 2022

ABSTRACT

INTRODUCTION: Parkinson disease (PD) affects approximately 1% of women and men worldwide, particularly older than 60 years. It is a multisystem and neurodegenerative disease with genetics and environmental factors that result in deficits in the production of neurotransmitters, including dopamine. The levodopa-carbidopa intestinal gel (LCIG) system delivers a continuous infusion of levodopa directly into the proximal small intestine via percutaneous endoscopic jejunostomy, largely bypassing gastric emptying and absorption problems and producing more stable plasma concentrations of levodopa, eliminating the development of motor complications (dyskinesias). The aim of this review was to summarize scientific evidence on the nursing role that, together with the multidisciplinary team, made the patient's choice in this therapeutic path (pre-LCIG phase). METHODS: A literature review was carried out, conducted on the MEDLINE databases (through PubMed), The Cochrane Library, Google Scholar, and CINAHL (through EBSCO). Relevant articles for the topic were found to identify indexed primary studies that investigated the relationship between the nurse and the patient/caregiver with PD who undertakes treatment with LCIG according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. RESULTS: Nineteen studies were included in the review. The selected studies suggested how the pre-LCIG phase of patient choice and the subsequent education and training could avoid selection errors for these therapeutic paths. CONCLUSION: Trained and specialized nursing staff who carry out an adequate pre-LCIG phase associated to the multidisciplinary team improved the choice of the patient and the start of treatment and, consequently, the quality of life of PD patients.
Distal femur: nail plate combination and the linked construct
Authors: Liporace Frank A. , Tang Alex , Jankowski Jaclyn M. , Yoon Richard S. 
Published: July 2022

Abstract

Summary:
Operative fixation of distal femur fractures in patients with osteoporotic bone can be challenging. Treatment with either lateral locking plate or retrograde intramedullary nail alone may not provide adequate fixation to allow for early mobilization. Rather, fixation using the nail plate combination (NPC) to treat distal femur fractures in the elderly may offer improved biomechanical stability to achieve immediate weight-bearing, especially in the setting of complex fracture patterns and osteoporosis. Here, we describe the rationale, step-by-step technique, and outcome following 2 cases: 1 patient treated with a true NPC procedure using retrograde intramedullary nail and standard locking plate, as well as a NPC procedure using a novel locking attaching washer plate.
Extreme nailing and immediate weight bearing constructs in fractures of the distal tibia
Authors: John Mitchell , Mir Hassan R. 
Published: July 2022

Abstract
Extraarticular fractures of the distal tibia can present as difficult but manageable lower extremity injuries. Historically, these injuries have been fixed in a myriad of ways. Early management with intramedullary nailing had higher complication rates due to the unique anatomical and biomechanical features of the distal tibia. Modern improvements in intramedullary nailing surgical techniques and implant design have significantly decreased complication rates and led to improvement in patient outcomes. Many surgeons protect weight bearing postoperatively, but recent literature suggests that patients may safely weight bear immediately following intramedullary fixation. This article reviews technique and implant design changes that have facilitated immediate safe weight bearing following intramedullary nailing of extraarticular distal tibia fractures.
Pharmacometric assessment of the in vivo antiviral activity of ivermectin in early symptomatic COVID-19
Authors: Schilling William HK , Jittamala Podjanee , Watson James A , Ekkapongpisit Maneerat , Siripoon Tanaya , Ngamprasertchai Thundon , Luvira Viravarn , Pongwilai Sasithon , Cruz Cintia , Callery James J , Boyd Simon , Kruabkontho Varaporn , Ngernseng Thatsanun , Tubprasert Jaruwan , Abdad Mohammad Yazid , Piaraksa Nattaporn , Suwannasin Kanokon , Hanboonkunupakarn Pongtorn , Hanboonkunupakarn Borimas , Sookprome Sakol , Poovorawan Kittiyod , Thaipadungpanit Janjira , Blacksell Stuart , Imwong Mallika , Tarning Joel , Taylor Walter RJ , Chotivanich Vasin , Sangketchon Chunlanee , Ruksakul Wiroj , Chotivanich Kesinee , Teixeira Mauro M , Pukrittayakamee Sasithon , Dondorp Arjen M , Day Nicholas PJ , Piyaphanee Watcharapong , Phumratanaprapin Weerapong , White Nicholas J 
Published: July 2022

ABSTRACTBackgroundThere is no generally accepted methodology for in vivo assessment of antiviral activity in SARS-CoV-2 infection. Ivermectin has been recommended widely as a treatment of COVID-19, but whether it has significant antiviral activity in vivo is uncertain.MethodsIn a multicentre open label, randomized, controlled adaptive platform trial, adult patients with early symptomatic COVID-19 were randomized to one of six treatment arms including high dose ivermectin (600µg/kg daily for seven days), the monoclonal antibodies casirivimab and imdevimab (600mg/600mg), and no study drug. Viral clearance rates were derived from daily duplicate oropharyngeal quantitative PCR measurements. This ongoing trial is registered at ClinicalTrials.gov (NCT05041907).ResultsRandomization to the ivermectin arm was stopped after enrolling 205 patients into all arms, as the prespecified futility threshold was reached. Compared with the no study drug arm, the mean estimated SARS-CoV-2 viral clearance following ivermectin was 9.1% slower [95%CI -27.2% to +11.8%; n=45 versus n=41], whereas in a preliminary analysis of the casirivimab/imdevimab arm it was 52.3% faster [95%CI +7.0% to +115.1%; n=10 (Delta variant) versus n=41].ConclusionsHigh dose ivermectin did not have measurable antiviral activity in early symptomatic COVID-19. Measured in this way viral clearance rate is a valuable pharmacodynamic measure in assessing antiviral COVID-19 therapeutics in vivo.Funding“Finding treatments for COVID-19: A phase 2 multi-centre adaptive platform trial to assess antiviral pharmacodynamics in early symptomatic COVID-19 (PLAT-COV)” is funded by the Wellcome Therapeutics Accelerator (223195/Z/21/Z).ImpactRate of viral clearance determined from daily duplicate oropharyngeal swabs over one week is an efficient measure of antiviral efficacy in early COVID-19 infection.High dose ivermectin did not demonstrate measurable antiviral activity in early symptomatic COVID-19 infection.
Factors influencing adoption of oral health promotion by antenatal care providers in Moyo district, North-Western Uganda
Authors: Lulu Patrick Madrama , Nanyingi Miisa 
Published: July 2022

AbstractBackgroundOral health promotion(OHP) during pregnancy is an important global public health and basic human right issue related to quality of life. Several statements and guidelines have been published emphasizing the need for improved oral health care of pregnant mothers, prenatal care providers have missed this critical opportunity. In this study, we assessed factors influencing adoption of oral health promotion by Antenatal care providers.Materials and MethodsA descriptive cross-sectional study design that employed both quantitative and qualitative data collection methods and analysis. 152 samples determined using Yamane’s 1967 and stratified sampling technique was used. Three FGDs and six KI interviews were held. Univariate, bivariate and multivariate analyses were done using SPSS (20.0) and ATLAS Ti for qualitative analysis.ResultsAdoption of OHP was low 28% (42). Factors influencing adoption were age of respondents(p=0.032*), level of care of health facility (p=0.004*), good understanding between dentists and ANC providers (aOR=0.283, 95%CI=0.084-0.958, p= 0.042*), availability of practice guideline for OHP in ANC (aOR=0.323, 95%CI=0.108-0.958, p= 0.043*), number of years at work (p=0.084), being knowledgeable (aOR=2.143, 95%CI=0.864-5.311, p= 0.100), having skills to advance OHP(aOR=0.734, 95%CI=0.272-1.984, p= 0.542), Management being good at influencing new practices (aOR=00.477.734, 95%CI=0.227-2.000, p= 0.477). More emphasis on national and local of oral health issues, continuous staff training on oral health, dissemination of National oral health policy (NOHP) were some of key issues that emerged from the qualitative results.ConclusionAdoption of OHP was low. This was attributed to age, number of years spent at work, level of health facility, having good understanding between dentists and ANC providers, availability of practice guidelines, dissemination of National oral health policy, continuous staff training. We recommend the current NOHP to be reviewed, develop prenatal OHC guidelines, enhance the capacity of ANC providers through training, collaboration with dentists and launch official adoption of OHP.
Impact of SARS-Cov-2 on Clinical Trial Unit Staff: The EPIC Observational Study
Authors: Phiri Peter , Yardley Lucy , Elliot Kathryn , Barnard-Kelly Katharine , Raymont Vanessa , Rathod Shanaya , Hu Jintong , Cavalini Heitor , Shi Jian Qing , Delanerolle Gayathri 
Published: July 2022

AbstractIntroductionClinical Trials Units (CTUs) are a key component of delivering non-commercial and commercial clinical research globally. Within the UK, CTUs are seen as a specialist and independent entity available to all researchers requiring support to setup, conduct and deliver clinical trials. Therefore, an involvement of a CTU is highly recommended by national regulators and positively accepted by funders, especially for drug and/or medical device and/or complex intervention trials.AimThis study aims to determine the challenges associated with the management of Covid-19 research managed via the CTU workforce, including the challenges associated with quality assurance, trial setup and data management. Additionally, this study will explore the by-stander effect on trial staff by way of evaluating the mental and physical health impact.Methods/ DesignThis is a mixed methods study. An online novel questionnaire survey study will be conducted among the UK CTU workforce. Quantitative data will be collected using the Qualtrics XM platform. We aim to recruit up to 1,500 CTU staff across the UK workforce. A subgroup sample will be randomly invited to take part in semi-structured interviews. Therefore, this survey will generate both quantitative and qualitative data inclusive of demographic data.ResultsThe findings will inform current initiatives and identify key themes for prioritising in further research to develop robust approaches to support CTU staff, including the development of a start-re-start framework for CTUs for any future pandemics relevant to developing and delivering communicable diseases and non-communicable diseases-based research.Strengths/LimitationsThe validation of the EPIC impact questionnaire used qualitative and quantitative methods which is a strength of the study. However, the study has a single timepoint to obtain data with the secondary outcome measures to be completed at two timepoints as this is an exploratory study attempting to obtain a wider data pool.
Th1 cells alter the inflammatory signature of IL-6 by channeling STAT transcription factors toAlu-like retroelements
Authors: Millrine David , Figueras Ana Cardus , Fernandez Javier Uceda , Andrews Robert , Szomolay Barbara , Cossins Benjamin C , Rice Christopher M. , Li Jasmine , Tyrrell Victoria J , McLeod Louise , Holmans Peter , O’Donnell Valerie B , Taylor Philip R , Turner Stephen J. , Jenkins Brendan J. , Jones Gareth W , Topley Nicholas , Williams Nigel M , Jones Simon A 
Published: July 2022

AbstractCytokines that signal via STAT1 and STAT3 transcription factors instruct decisions affecting tissue homeostasis, anti-microbial host defense, and inflammation-induced tissue injury. To understand the coordination of these activities, we applied RNA-seq, ChIP-seq, and ATAC-seq to identify the transcriptional output of STAT1 and STAT3 in peritoneal tissues during acute resolving inflammation and inflammation primed to drive fibrosis. Bioinformatics focussed on the transcriptional signature of the immuno-modulatory cytokine IL-6 in both settings and examined how pro-fibrotic IFNγ-secreting CD4+T-cells altered the interpretation of STAT1 and STAT3 cytokine cues. In resolving inflammation, STAT1 and STAT3 cooperated to drive stromal gene expression affecting anti-microbial immunity and tissue homeostasis. The introduction of IFNγ-secreting CD4+T-cells altered this transcriptional program and channeled STAT1 and STAT3 to a previously latent GAS motif inAlu-like elements. STAT1 and STAT3 binding to this conserved sequence revealed evidence of reciprocal cross-regulation and gene signatures relevant to pathophysiology. Thus, we propose that effector T-cells re-tune the transcriptional output of IL-6 by shaping a regulatory interplay between STAT1 and STAT3 in inflammation.
Identification of a Papain-Like Protease Inhibitor with Potential for Repurposing in Combination with an Mpro Protease Inhibitor for Treatment of SARS-CoV-2
Authors: Campagna Jesus , Jagodzinska Barbara , Alvarez Pablo , Yeun Constance , Spilman Patricia , Enquist Kathryn M. , Cohn Whitaker , Fajtová Pavla , O’Donoghue Anthony J. , Arumugaswami Vaithilingaraja , Li Melody M.H. , Damoiseaux Robert , John Varghese 
Published: July 2022

ABSTRACTSARS-CoV-2 requires two cysteine proteases for viral polypeptide processing to allow maturation and replication: the 3C-like protease also known as the Main protease (Mpro) and the papain-like protease (PLpro). In addition to its critical role in viral replication, PLpro removes post-translational modifications like ubiquitin and interferon-stimulated gene product 15 (ISG15) from host proteins through its deubiquitinase domain, leading to host immunosuppression and increased ability of the virus to evade the host antiviral immune response. Through screening of a custom clinical compound library, we identified eltrombopag (DDL-701), a thrombopoietin receptor agonist, as having PLpro inhibitory activity that is sustained in the presence of the Mpro inhibitor nirmatrelvir. DDL-701 also suppressed both the deubiquitinase and ISG15 cleavage activities of PLpro. In addition, DDL-701 partially restored interferon-β induction – an element of the host immune response - in an in vitro model system. Further, modeling and docking studies suggest DDL-701 interacts with the active site region of the PLpro enzyme and pilot pharmacokinetic studies indicate it is brain permeable. DDL-701 is already approved for treatment of thrombocytopenia and has previously been shown to achieve human plasma levels after oral dosing that is above the IC50 needed for it to exert its PLpro inhibitory activity in vivo. In addition, it has also been reported to have antiviral efficacy against SARS-CoV-2. DDL-701 thus represents a drug that can immediately be repurposed and undergo clinical evaluation as a PLpro inhibitor that may be most effectively used in a protease inhibitor cocktail with an Mpro inhibitor such as nirmatrelvir (Paxlovid) for the treatment of COVID-19.