bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation and improvement the safety of total marrow irradiation with helical tomotherapy using repeat failure mode and effects analysis
Authors: Shen Jiuling , Wang Xiaoyong , Deng Di , Gong Jian , Tan Kang , Zhao Hongli , Bao Zhirong , Xiao Jinping , Liu An , Zhou Yunfeng , Liu Hui , Xie Conghua 
Published: December 2019

Abstract
Background & purpose
Helical tomotherapy has been applied to total marrow irradiation (HT-TMI). Our objective was to apply failure mode and effects analysis (FMEA) two times separated by 1 year to evaluate and improve the safety of HT-TMI.

Materials and methods
A multidisciplinary team was created. FMEA consists of 4 main steps: (1) Creation of a process map; (2) Identification of all potential failure mode (FM) in the process; (3) Evaluation of the occurrence (O), detectability (D) and severity of impact (S) of each FM according to a scoring criteria (1–10), with the subsequent calculation of the risk priority number (RPN=O*D*S) and (4) Identification of the feasible and effective quality control (QC) methods for the highest risks. A second FMEA was performed for the high-risk FMs based on the same risk analysis team in 1 year later.

Results
A total of 39 subprocesses and 122 FMs were derived. First time RPN ranged from 3 to 264.3. Twenty-five FMs were defined as being high-risk, with the top 5 FMs (first RPN/ second RPN): (1) treatment couch movement failure (264.3/102.8); (2) section plan dose junction error in delivery (236.7/110.4); (3) setup check by megavoltage computed tomography (MVCT) failure (216.8/94.6); (4) patient immobilization error (212.5/90.2) and (5) treatment interruption (204.8/134.2). A total of 20 staff members participated in the study. The second RPN value of the top 5 high-risk FMs were all decreased.

Conclusion
QC interventions were implemented based on the FMEA results. HT-TMI specific treatment couch tests; the arms immobilization methods and strategy of section plan dose junction in delivery were proved to be effective in the improvement of the safety.
Modern instant messaging platform for postoperative follow-up of patients after total joint arthroplasty may reduce re-admission rate
Authors: Zheng Qing-Yuan , Geng Lei , Ni Ming , Sun Jing-Yang , Ren Peng , Ji Quan-Bo , Li Jun-Cheng , Zhang Guo-Qiang 
Published: December 2019

Abstract
Background
Follow-up after artificial joint replacement greatly helps achieve surgical outcomes. Mobile internet technology and mobile terminal equipment may increase the effectiveness of artificial joint replacement. However, only a few studies have evaluated the effectiveness of this technology. We aimed to analyze the reasons and outcomes of patients who used the instant messaging platform after undergoing artificial joint replacement.

Methods
Among the 548 cases of arthroplasty (250 hips, 298 knees) performed between December 2015 and June 2018 in the Department of Joint Surgery of our institution; 358 (164 hip joints, 194 knee joints) participated in instant messaging platform consultation, whereas the remaining 190 (86 hip joints, 104 knee joints) participated in traditional telephone consultation, as a control group. Follow-up time was from December 2015 to August 2018 (follow-up period was 2–32 months). Data on age, sex, type of surgery, date of surgery, date of discharge, and length of hospital stay were collected from electronic medical records.

Results
We analyzed the consultation contents of 358 patients who participated in instant messaging platform consultation. Counseling was mainly related to pain (13.6%), appointment review (12.4%), activity problems (10.5%), and incision problems (8.9%). Most problems were resolved through online guidance, with 8.4% of patients requiring only outpatient treatment and 2.5% of patients requiring rehospitalization. A total of 190 patients were followed up through traditional telephone consultation; 6.8% of patients required outpatient department treatment and 7.4% were eventually re-admitted.

Conclusion
The instant messaging platform consultation service effectively informs patients of potential postoperative problems and helps resolve them. It allows early detection and management of postoperative adverse events, including problems related to medication, wound, and activity, thereby effectively reducing readmission rate.
Approaching the challenges of MKK3/p38delta MAPK targeting for therapeutic purpose in colorectal cancer
Authors: Stramucci Lorenzo , Bossi Gianluca 
Published: December 2019

AbstractMKK3 is a member of the dual specificity kinase group specific upstream activator of p38 MAPK proteins. We originally identified MKK3 as mutant p53 (mutp53) gain-of-function (GOF) upregulated target gene in different tumor models. To deeply investigate the MKK3 functions in cancer, taking advantage of a panel of authenticated colorectal cancer (CRC) lines and primary colonocytes, we found that MKK3 activates specifically p38delta MAPK protein, which signaling is further triggered by 5-fluorouracil (5-FU) treatments, a largely adopted chemotherapeutic drug in CRC clinical practice. The overall achieved results proposed the MKK3/p38delta MAPK as relevant molecular axis involved in abrogating efficacy to 5-FU treatments in CRC. This commentary will provide an overall discussion of the results that have been achieved contextualizing them in the overview of the knowledge in the p38 MAPK field in cancer disease.
Driving pressure is not associated with mortality in mechanically ventilated patients without ARDS
Authors: Lanspa Michael J. , Peltan Ithan D. , Jacobs Jason R. , Sorensen Jeffrey S. , Carpenter Lori , Ferraro Jeffrey P. , Brown Samuel M. , Berry Jay G. , Srivastava Raj , Grissom Colin K. 
Published: December 2019

Abstract
Background
In patients with acute respiratory distress syndrome (ARDS), low tidal volume ventilation has been associated with reduced mortality. Driving pressure (tidal volume normalized to respiratory system compliance) may be an even stronger predictor of ARDS survival than tidal volume. We sought to study whether these associations hold true in acute respiratory failure patients without ARDS.

Methods
This is a retrospectively cohort analysis of mechanically ventilated adult patients admitted to ICUs from 12 hospitals over 2 years. We used natural language processing of chest radiograph reports and data from the electronic medical record to identify patients who had ARDS. We used multivariable logistic regression and generalized linear models to estimate associations between tidal volume, driving pressure, and respiratory system compliance with adjusted 30-day mortality using covariates of Acute Physiology Score (APS), Charlson Comorbidity Index (CCI), age, and PaO2/FiO2 ratio.

Results
We studied 2641 patients; 48% had ARDS (n = 1273). Patients with ARDS had higher mean APS (25 vs. 23, p < .001) but similar CCI (4 vs. 3, p = 0.6) scores. For non-ARDS patients, tidal volume was associated with increased adjusted mortality (OR 1.18 per 1 mL/kg PBW increase in tidal volume, CI 1.04 to 1.35, p = 0.010). We observed no association between driving pressure or respiratory compliance and mortality in patients without ARDS. In ARDS patients, both ΔP (OR1.1, CI 1.06–1.14, p < 0.001) and tidal volume (OR 1.17, CI 1.04–1.31, p = 0.007) were associated with mortality.

Conclusions
In a large retrospective analysis of critically ill non-ARDS patients receiving mechanical ventilation, we found that tidal volume was associated with 30-day mortality, while driving pressure was not.
S100a4 upregulation in Pik3caH1047R;Trp53R270H;MMTV-Cre-driven mammary tumors promotes metastasis
Authors: Yuan Wenlin , Goldstein Leonard D. , Durinck Steffen , Chen Ying-Jiun , Nguyen Thong T. , Kljavin Noelyn M. , Sokol Ethan S. , Stawiski Eric W. , Haley Benjamin , Ziai James , Modrusan Zora , Seshagiri Somasekar 
Published: December 2019

Abstract
Background
PIK3CA mutations are frequent in human breast cancer. Pik3caH1047R mutant expression in mouse mammary gland promotes tumorigenesis. TP53 mutations co-occur with PIK3CA mutations in human breast cancers. We previously generated a conditionally activatable Pik3caH1047R;MMTV-Cre mouse model and found a few malignant sarcomatoid (spindle cell) carcinomas that had acquired spontaneous dominant-negative Trp53 mutations.

Methods
A Pik3caH1047R;Trp53R270H;MMTV-Cre double mutant mouse breast cancer model was generated. Tumors were characterized by histology, marker analysis, transcriptional profiling, single-cell RNA-seq, and bioinformatics. Cell lines were developed from mutant tumors and used to identify and confirm genes involved in metastasis.

Results
We found Pik3caH1047R and Trp53R270H cooperate in driving oncogenesis in mammary glands leading to a shorter latency than either alone. Double mutant mice develop multiple histologically distinct mammary tumors, including adenocarcinoma and sarcomatoid (spindle cell) carcinoma. We found some tumors to be invasive and a few metastasized to the lung and/or the lymph node. Single-cell RNA-seq analysis of the tumors identified epithelial, stromal, myeloid, and T cell groups. Expression analysis of the metastatic tumors identified S100a4 as a top candidate gene associated with metastasis. Metastatic tumors contained a much higher percentage of epithelial–mesenchymal transition (EMT)-signature positive and S100a4-expressing cells. CRISPR/CAS9-mediated knockout of S100a4 in a metastatic tumor-derived cell line disrupted its metastatic potential indicating a role for S100a4 in metastasis.

Conclusions
Pik3caH1047R;Trp53R270H;MMTV-Cre mouse provides a preclinical model to mimic a subtype of human breast cancers that carry both PIK3CA and TP53 mutations. It also allows for understanding the cooperation between the two mutant genes in tumorigenesis. Our model also provides a system to study metastasis and develop therapeutic strategies for PIK3CA/TP53 double-positive cancers. S100a4 found involved in metastasis in this model can be a potential diagnostic and therapeutic target.
Influence of Early versus Late supplemental ParenteraL Nutrition on long-term quality of life in ICU patients after gastrointestinal oncological surgery (hELPLiNe): study protocol for a randomized controlled trial
Authors: Piwowarczyk Paweł , Kutnik Paweł , Borys Michał , Rypulak Elżbieta , Potręć-Studzińska Beata , Sysiak-Sławecka Justyna , Czarnik Tomasz , Czuczwar Mirosław 
Published: December 2019

Abstract
Background
Nutrition plays a major role in intensive care unit (ICU) treatment, influencing ICU length of stay and patient’s survival. If preferable enteral nutrition administration is not feasible, ESPEN and ASPEN guidelines recommend initiation of a supplemental parenteral route between the first and seventh day, but exact timing remains elusive. While rapid development in critical care enabled significant reduction in the mortality rate of ICU patients, this improvement also tripled the number of patients going to rehabilitation. Thus, it is quality of life after ICU that has become the subject of interest of clinicians and healthcare policy-makers. A growing body of evidence indicates that protein turnover in the early phase of critical illness may play a crucial role in the preservation of lean body mass. A negative protein balance may lead to muscle wasting that persists weeks and months after ICU stay, resulting in deterioration of physical functioning. Folliwing oncological gastrointestinal tract surgery, patients are threatened with negative protein turnover due to cancer and extensive surgical insult.

Methods
This is a multi-centre, single-blinded, randomised controlled trial. The study population includes patients admitted to ICU units after major oncological gastrointestinal surgery that require supplemental parenteral nutrition. After initiation of enteral nutrition, the intervention group receives remaining daily requirement via supplemental parenteral nutrition on the first day of ICU stay while the control group is not supplemented parenterally until the seventh day of ICU stay while enteral nutrition is gradually increased.
Primary endpoint: long-term quality of life measured in the physical component score (PCS) of SF-36 questionnaire at 3 and 6 months after ICU admission.

Discussion
To our knowledge, this is the first trial to investigate the influence of early supplemental parenteral nutrition on long-term quality of life after major oncological gastrointestinal surgery. We assume that, particularly in this population of patients, early supplemental parenteral nutrition may increase the long-term quality of life. The study construction also allows establishment of patients’ PCS SF-36 score prior to surgery and mean change in PCS SF-36 score during the recovery period, which is rarely seen in studies on critically ill patients.

Trial registration
ClinicalTrials.gov: NCT03699371 registered on 12 October 2018.
Virtual reality as an adjunct to anesthesia in the operating room
Authors: Faruki Adeel , Nguyen Thy , Proeschel Samantha , Levy Nadav , Yu Jessica , Ip Victoria , Mueller Ariel , Banner-Goodspeed Valerie , O’Gara Brian 
Published: December 2019

AbstractBackgroundAdvancements in virtual reality (VR) technology have resulted in its expansion into health care. Preliminary studies have found VR to be effective as an adjunct to anesthesia to reduce pain and anxiety for patients during upper gastrointestinal endoscopies, dental procedures and joint arthroplasties. Current standard care practice for upper extremity surgery includes a combination of regional anesthesia and intraoperative propofol sedation. Commonly, patients receive deep propofol sedation during these cases, leading to potentially avoidable risks of over-sedation, hypotension, upper airway obstruction, and apnea. The objective of this study is to evaluate the effectiveness of VR technology to promote relaxation for patients undergoing upper extremity surgery, thereby reducing intraoperative anesthetic requirements and improving the perioperative patient experience.MethodsIn this single-center, randomized controlled trial, 40 adult patients undergoing upper extremity orthopedic surgery will be randomly allocated to either intraoperative VR immersion or usual care. VR immersion is designed to provide patients with a relaxing virtual environment to alleviate intraoperative anxiety. All patients receive a peripheral nerve block prior to surgery. Patients in the intervention group will select videos or immersive environments which will be played in the VR headset during surgery. An anesthesia provider will perform their usual clinical responsibilities intraoperatively and can administer anesthetic medications if and when clinically necessary. Patients in the control arm will undergo perioperative anesthesia according to standard care practice. The primary outcome is the difference in intraoperative propofol dose between the groups. Secondary outcomes include postoperative analgesia requirements and pain scores, length of stay in the postanesthesia care unit, overall patient satisfaction and postoperative functional outcomes.DiscussionIt is unknown whether the use of VR during upper extremity surgery can reduce intraoperative anesthetic requirements, reduce perioperative complications, or improve the postoperative patient experience. A positive result from this clinical trial would add to the growing body of evidence that demonstrates the effectiveness of VR as an adjunct to anesthesia in reducing intraoperative pain and anxiety for multiple types of procedure. This could lead to a change in practice, with the introduction of a nonpharmacologic intervention potentially reducing the burden of over-sedation while still providing a satisfactory perioperative experience.Trial registrationClinicalTrials.gov,NCT03614325. Registered on 9 July 2018.
A two-phase substrate model for enzymatic hydrolysis of lignocellulose: application to batch and continuous reactors
Authors: Lischeske James J. , Stickel Jonathan J. 
Published: December 2019

Abstract
Background
Enzymatic hydrolysis continues to have a significant projected production cost for the biological conversion of biomass to fuels and chemicals, motivating research into improved enzyme and reactor technologies in order to reduce enzyme usage and equipment costs. However, technology development is stymied by a lack of accurate and computationally accessible enzymatic-hydrolysis reaction models. Enzymatic deconstruction of cellulosic materials is an exceedingly complex physico-chemical process. Models which elucidate specific mechanisms of deconstruction are often too computationally intensive to be accessible in process or multi-physics simulations, and empirical models are often too inflexible to be effectively applied outside of their batch contexts. In this paper, we employ a phenomenological modeling approach to represent rate slowdown due to substrate structure (implemented as two substrate phases) and feedback inhibition, and apply the model to a continuous reactor system.

Results
A phenomenological model was developed in order to predict glucose and solids concentrations in batch and continuous enzymatic-hydrolysis reactors from which liquor is continuously removed by ultrafiltration. A series of batch experiments were performed, varying initial conditions (solids, enzyme, and sugar concentrations), and best-fit model parameters were determined using constrained nonlinear least-squares methods. The model achieved a good fit for overall sugar yield and insoluble solids concentration, as well as for the reduced rate of sugar production over time. Additionally, without refitting model coefficients, good quantitative agreement was observed between results from continuous enzymatic-hydrolysis experiments and model predictions. Finally, the sensitivity of the model to its parameters is explored and discussed.

Conclusions
Although the phenomena represented by the model correspond to behaviors that emerge from clusters of mechanisms, and hence a set of model coefficients are unique to the substrate and the enzyme system, the model is efficient to solve and may be applied to novel reactor schema and implemented in computational fluid dynamics (CFD) simulations. Hence, this modeling approach finds the right balance between model complexity and computational efficiency. These capabilities have broad application to reactor design, scale-up, and process optimization.
Focused ultrasound-induced blood-brain barrier opening improves adult hippocampal neurogenesis and cognitive function in a cholinergic degeneration dementia rat model
Authors: Shin Jaewoo , Kong Chanho , Lee Jihyeon , Choi Bo Young , Sim Jiyeon , Koh Chin Su , Park Minkyung , Na Young Cheol , Suh Sang Won , Chang Won Seok , Chang Jin Woo 
Published: December 2019

AbstractBackgroundThe persistence of adult hippocampal neurogenesis (AHN) is sharply decreased in Alzheimer’s disease (AD). The neuropathologies of AD include the presence of amyloid-β deposition in plaques, tau hyperphosphorylation in neurofibrillary tangles, and cholinergic system degeneration. The focused ultrasound (FUS)-mediated blood-brain barrier opening modulates tau hyperphosphorylation, the accumulation of amyloid-β proteins, and increases in AHN. However, it remains unclear whether FUS can modulate AHN in cholinergic-deficient conditions. In this study, we investigated the effect of FUS on AHN in a cholinergic degeneration rat model of dementia.MethodsAdult male Sprague-Dawley rats (n = 48; 200–250 g) were divided into control (phosphate-buffered saline injection), 192 IgG-saporin (SAP), and SAP+FUS groups; in the two latter groups, SAP was injected bilaterally into the lateral ventricle. We applied FUS to the bilateral hippocampus with microbubbles. Immunohistochemistry, enzyme-linked immunosorbent assay, immunoblotting, 5-bromo-2′-deoxyuridine labeling, an acetylcholinesterase assay, and the Morris water maze test were performed to assess choline acetyltransferase, acetylcholinesterase activity, brain-derived neurotrophic factor expression, neural proliferation, and spatial memory, respectively. Statistical significance of differences in between groups was calculated using one-way and two-way analyses of variance followed by Tukey’s multiple comparison test to determine the individual and interactive effects of FUS on immunochemistry and behavioral analysis.P < 0.05 was considered significant.ResultsCholinergic degeneration in rats significantly decreased the number of choline acetyltransferase neurons (P < 0.05) in the basal forebrain, as well as AHN and spatial memory function. Rats that underwent FUS-mediated brain-blood barrier opening exhibited significant increases in brain-derived neurotrophic factor (BDNF;P < 0.05), early growth response protein 1 (EGR1) (P < 0.01), AHN (P < 0.01), and acetylcholinesterase activity in the frontal cortex (P < 0.05) and hippocampus (P < 0.01) and crossing over (P < 0.01) the platform in the Morris water maze relative to the SAP group after sonication.ConclusionsFUS treatment increased AHN and improved spatial memory. This improvement was mediated by increased hippocampal BDNF and EGR1. FUS treatment may also restore AHN and protect against neurodegeneration, providing a potentially powerful therapeutic strategy for AD.
Ceboruco hazard map: part I - definition of hazard scenarios based on the eruptive history
Authors: Sieron Katrin , Ferres Dolors , Siebe Claus , Capra Lucia , Constantinescu Robert , Agustín-Flores Javier , González Zuccolotto Karime , Böhnel Harald , Connor Laura , Connor Charles B. , Groppelli Gianluca 
Published: December 2019

AbstractOf the 48 volcanoes in Mexico listed as potentially active by the National Center for Disaster Prevention (CENAPRED), Ceboruco, located in the western Trans-Mexican Volcanic Belt, is considered among the 5 most hazardous. Its recent eruptive history includes a large magnitude Plinian (VEI 6) eruption ~ 1000 years ago and the historical 1870–1875 vulcanian (VEI 3) eruption, as well as recent fumarolic and seismic activity.Ceboruco is a relatively young (< 400,000 years) stratovolcano characterized by abrupt changes in eruptive behavior. Individual eruptive episodes have great variations in style (effusive andesitic to highly-explosive rhyodacitic) and duration. These factors complicate hazard assessment.Three main eruptive scenarios of different magnitudes (large, intermediate, small) and eruption characteristics (likelihood of occurrence: high, medium, small) have been identified and will be presented as a background to build the volcanic hazard map for Ceboruco volcano (presented in part II of this work). Here, we report on the detailed eruptive history, with emphasis on the volcanic products of each of the eruptions, in order to identify those deposits that can serve as a reference for calibrating the modeling software (Tephra2 and Hazmap for ash fallout, Eject! code for ballistics, Etna Lava Flow Model for lava flows, Titan2D for pyroclastic density currents, and Flo-2D and LaharZ for lahars) that will be used in further steps to simulate different volcanic phenomena and lead to the construction of the hazard map.