bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between indoor environmental quality in schools and symptom reporting in pupil-administered questionnaires
Authors: Savelieva Kateryna , Marttila Tero , Lampi Jussi , Ung-Lanki Sari , Elovainio Marko , Pekkanen Juha
Published: December 2019

Background

The associations between indoor environmental quality (IEQ) in homes and symptom reporting of children have been extensively studied, but only few large-scale studies have been done in schools. We examined associations between expert-assessed IEQ in schools and pupils’ reporting of different symptoms, and whether associations were stronger if participants relate symptoms to the school environment.

Methods

The questionnaire survey was done in all primary and secondary schools in two areas of Helsinki, Finland. Primary school pupils (grade 3–6,n = 8775, 99 school-buildings) and secondary school pupils (grade 7–9,n = 3410, 30 school-buildings) reported their symptoms. Symptoms were combined into respiratory, lower respiratory, eye, skin, and general symptom groups. Surveys were also done among the parents of the primary school pupils (grade 1–6,n = 3540, 88 school buildings), but results are reported only in the supplement due to the low response rate (20% in 2017 and 13% in 2018). The associations between IEQ and symptoms were analyzed using multilevel logistic regression analysis.

Results

Several of the IEQ indicators were highly correlated and indicators were therefore mainly analyzed by combining them into a summary score and into latent classes. Dose-response associations were found between IEQ problems and higher reporting of respiratory and general symptoms among both primary and secondary school pupils. Some associations were also observed with lower respiratory and skin symptoms, but not with eye symptoms. The associations were somewhat stronger with symptoms related to the school environment compared to symptoms reported without such relation: for a unit change in IEQ summary score and respiratory symptoms in primary schools, odds ratios were 1.07 (95% CI 1.02–1.06) and 1.04 (95% CI 1.04–1.10), and in secondary schools 1.09 (95% CI 1.01–1.09) and 1.05 (95% CI 1.02–1.17), respectively.

Conclusions

Expert-assessed IEQ problems in schools were associated with increased reporting of especially respiratory and general symptoms. The associations were only somewhat stronger in magnitude for symptoms reported in relation to the school environment compared to symptoms reported without such relation.
The let-7 family of microRNAs suppresses immune evasion in head and neck squamous cell carcinoma by promoting PD-L1 degradation
Authors: Yu Dan , Liu Xueshibojie , Han Guanghong , Liu Yan , Zhao Xue , Wang Di , Bian Xiaomin , Gu Tingting , Wen Lianji
Published: December 2019

Background

Accumulation of immunosuppressive protein programmed death-ligand 1 (PD-L1) has been documented in several cancers and contributes to the evasion of the host immune system. However, cancer cell-intrinsic signaling-dependent control of PD-L1 expression remains to be elucidated. Herein, we aimed to identify the let-7 family of microRNAs as candidates that up-regulate tumor cell PD-L1 expression and mediates immune evasion of head and neck squamous cell carcinoma (HNSCC).

Methods

The expression of let-7 family and PD-L1 was quantified in HNSCC tissues and adjacent normal tissues. PD-L1 degradation was evaluated in HNSCC cells in response to elevated expressions of let-7a or let-7b. The regulation of let-7 family on PD-L1 degradation through a mechanism involving T-cell factor-4 (TCF-4) control of β-catenin/STT3 pathway was evaluated. Immune recognition of HNSCC in vivo was examined in subcutaneous tumor-bearing C3H mice in the presence of let-7a/b and/or CTLA-4 antibody.

Results

The let-7 family were significantly down-regulated in the context of HNSCC, sharing a negative correlation with PD-L1 expression. Glycosylated PD-L1 was detected in HNSCC cells, which was reduced by let-7a/b over-expression. TCF-4, the target of let-7a/b, activated the β-catenin/STT3 pathway and promoted PD-L1 degradation. In vivo analysis demonstrated that let-7a/b over-expression potentiated anticancer immunotherapy by CTLA-4 blockade.

Conclusions

Taken together, our findings highlight targeting let-7 family as a potential strategy to enhance immune checkpoint therapy for HNSCC.
Rural physical activity interventions in the United States: a systematic review and RE-AIM evaluation
Authors: Bhuiyan Nishat , Singh Pritika , Harden Samantha M. , Mama Scherezade K.
Published: December 2019

Background

Previous reviews of rural physical activity interventions were focused on intervention effectiveness and had reported overall mixed findings. The purpose of this systematic review was to apply the Reach, Efficacy, Adoption, Implementation and Maintenance (RE-AIM) framework to evaluate the extent to which rural physical activity interventions in the U.S. have reported on dimensions of internal and external validity and to offer suggestions for future physical activity interventions for rural U.S. populations.

Methods

Pubmed, PsychINFO, CINAHL, PAIS, and Web of Science were searched through February 2019 to identify physical activity intervention studies conducted in rural regions in the U.S. with adult populations. Titles, abstracts, and full texts of articles were reviewed against inclusion and exclusion criteria. Data extraction from included articles included a summary of study details, rural classification system used, and the presence or absence of a total 61 RE-AIM indicators, including reach (n = 13), efficacy/effectiveness (n = 10), adoption (n = 21), implementation (n = 9), and maintenance (n = 8).

Results

A total of 40 full-text articles representing 29 unique studies were included. Classifications of rurality included self-statements by authors (n = 19, 65.5%), population/census-based definitions (n = 3, 10.3%), Rural Urban Continuum Codes (n = 3, 10.3%), Rural Urban Commuting Area codes (n = 2, 6.9%), the 2014 Alabama Rural Health Association classification system (n = 1, 3.4%) and the U.S. Office of Management and Budget classification system (n = 1, 3.4%). Individual studies reported between 14.8 to 52.5% of total RE-AIM indicators. Studies reported 15.4 to 84.6% indicators for reach; 20.0 to 70.0% indicators for efficacy/effectiveness; 4.8 to 47.6% indicators for adoption; 11.1 to 88.9% indicators for implementation; and 0 to 25.0% indicators for maintenance.

Conclusions

We found an overall poor reporting of components related to external validity, which hinders the generalizability of intervention findings, and a lack of consistency in the definition of rurality. Future research should focus on balancing factors of internal and external validity, and should aim to develop a greater understanding of how rurality influences health and behavior to provide contextual knowledge needed to advance the translation of physical activity interventions into practice in rural communities and reduce rural health disparities.

Trial registration

The review protocol was registered with PROSPERO: CRD42019116308.
The nature and extent of upper limb associated reactions during walking in people with acquired brain injury
Authors: Kahn Michelle B. , Clark Ross A. , Williams Gavin , Bower Kelly J. , Banky Megan , Olver John , Mentiplay Benjamin F.
Published: December 2019

Background

Upper limb associated reactions (ARs) are common in people with acquired brain injury (ABI). Despite this, there is no gold-standard outcome measure and no kinematic description of this movement disorder. The aim of this study was to determine the upper limb kinematic variables most frequently affected by ARs in people with ABI compared with a healthy cohort at matched walking speed intention.

Methods

A convenience sample of 36 healthy control adults (HCs) and 42 people with ABI who had upper limb ARs during walking were recruited and underwent assessment of their self-selected walking speed using the criterion-reference three dimensional motion analysis (3DMA) at Epworth Hospital, Melbourne. Shoulder flexion, abduction and rotation, elbow flexion, forearm rotation and wrist flexion were assessed. The mean angle, standard deviation (SD), peak joint angles and total joint angle range of motion (ROM) were calculated for each axis across the gait cycle. On a group level, ANCOVA was used to assess the between-group differences for each upper limb kinematic outcome variable. To quantify abnormality prevalence on an individual participant level, the percentage of ABI participants that were outside of the 95% confidence interval of the HC sample for each variable were calculated.

Results

There were significant between-group differences for all elbow and shoulder abduction outcome variables (p < 0.01), most shoulder flexion variables (except for shoulder extension peak), forearm rotation SD and ROM and for wrist flexion ROM. Elbow flexion and shoulder abduction were the axes most frequently affected by ARs. Despite the elbow being the most prevalently affected (38/42, 90%), a large proportion of participants had abnormality, defined as ±1.96 SD of the HC mean, present at the shoulder (32/42, 76%), forearm (20/42, 48%) and wrist joints (10/42, 24%).

Conclusion

This study provides valuable information on ARs, and highlights the need for clinical assessment of ARs to include all of the major joints of the upper limb. This may inform the development of a criterion-reference outcome measure or classification system specific to ARs.
Roles of the highly conserved amino acids in the second receptor binding site of the Newcastle disease virus HN protein
Authors: Liu Yaqing , Chi Miaomiao , Liu Ying , Wen Hongling , Zhao Li , Song Yanyan , Liu Na , Wang Zhiyu
Published: December 2019

Background

The paramyxovirus haemagglutinin-neuraminidase (HN) is a multifunctional protein that is responsible for attachment to receptors, removal of receptors from infected cells to prevent viral self-aggregation (neuraminidase, NA) and fusion promotion. It is commonly accepted that there are two receptor binding sites in the globular head of HN, and the second receptor binding site is only involved in the function of receptor binding and fusion promotion.

Methods

10 conserved residues in the second receptor binding site of Newcastle disease virus (NDV) HN were chosen and substituted to alanine (A). The desired mutants were examined to detect the functional change in hemadsorption (HAD) ability, NA activity and fusion promotion ability.

Results

The HAD and fusion promotion ability of mutants C172A, R174A, C196A, D198A, Y526A and E547A were abolished. Compared with wild-type (wt) HN, the HAD of mutants T167A, S202A and R516A decreased to 55.81, 44.53, 69.02%, respectively, and the fusion promotion ability of these three mutants decreased to 54.74, 49.46, 65.26%, respectively; however, mutant G171A still maintained fusion promotion ability comparable with wt HN but had impaired HAD ability. All the site-directed mutations altered the NA activity of NDV HN without affecting protein cell surface expression.

Conclusions

The data suggest that mutants C172A, R174A, C196A, D198A, Y526A and E547A do not allow the conformational change that is required for fusion promotion ability and HAD activity, while the other mutants only affect the conformational change to a limited extent, except mutant G171A with intact fusion promotion ability. Overall, the conserved amino acids in the second receptor binding site, especially residues C172, R174, C196, D198, Y526 and E547, are crucial to normal NDV HN protein function.
PI-Plat: a high-resolution image-based 3D reconstruction method to estimate growth dynamics of rice inflorescence traits
Authors: Sandhu Jaspreet , Zhu Feiyu , Paul Puneet , Gao Tian , Dhatt Balpreet K. , Ge Yufeng , Staswick Paul , Yu Hongfeng , Walia Harkamal
Published: December 2019

Background

Recent advances in image-based plant phenotyping have improved our capability to study vegetative stage growth dynamics. However, more complex agronomic traits such as inflorescence architecture (IA), which predominantly contributes to grain crop yield are more challenging to quantify and hence are relatively less explored. Previous efforts to estimate inflorescence-related traits using image-based phenotyping have been limited to destructive end-point measurements. Development of non-destructive inflorescence phenotyping platforms could accelerate the discovery of the phenotypic variation with respect to inflorescence dynamics and mapping of the underlying genes regulating critical yield components.

Results

The major objective of this study is to evaluate post-fertilization development and growth dynamics of inflorescence at high spatial and temporal resolution in rice. For this, we developed the Panicle Imaging Platform (PI-Plat) to comprehend multi-dimensional features of IA in a non-destructive manner. We used 11 rice genotypes to capture multi-view images of primary panicle on weekly basis after the fertilization. These images were used to reconstruct a 3D point cloud of the panicle, which enabled us to extract digital traits such as voxel count and color intensity. We found that the voxel count of developing panicles is positively correlated with seed number and weight at maturity. The voxel count from developing panicles projected overall volumes that increased during the grain filling phase, wherein quantification of color intensity estimated the rate of panicle maturation. Our 3D based phenotyping solution showed superior performance compared to conventional 2D based approaches.

Conclusions

For harnessing the potential of the existing genetic resources, we need a comprehensive understanding of the genotype-to-phenotype relationship. Relatively low-cost sequencing platforms have facilitated high-throughput genotyping, while phenotyping, especially for complex traits, has posed major challenges for crop improvement. PI-Plat offers a low cost and high-resolution platform to phenotype inflorescence-related traits using 3D reconstruction-based approach. Further, the non-destructive nature of the platform facilitates analyses of the same panicle at multiple developmental time points, which can be utilized to explore the genetic variation for dynamic inflorescence traits in cereals.
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

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

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

MKK3 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

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

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

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

Background

Advancements 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.

Methods

In 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.

Discussion

It 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 registration

ClinicalTrials.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

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

Background

The 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.

Methods

Adult 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.

Results

Cholinergic 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.

Conclusions

FUS 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

Of 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.
Unsupervised adaptation of PLDA models for broadcast diarization
Authors: Viñals Ignacio , Ortega Alfonso , Villalba Jesús , Miguel Antonio , Lleida Eduardo
Published: December 2019

We present a novel model adaptation approach to deal with data variability for speaker diarization in a broadcast environment. Expensive human annotated data can be used to mitigate the domain mismatch by means of supervised model adaptation approaches. By contrast, we propose an unsupervised adaptation method which does not need for in-domain labeled data but only the recording that we are diarizing. We rely on an inner adaptation block which combines Agglomerative Hierarchical Clustering (AHC) and Mean-Shift (MS) clustering techniques with a Fully Bayesian Probabilistic Linear Discriminant Analysis (PLDA) to produce pseudo-speaker labels suitable for model adaptation. We propose multiple adaptation approaches based on this basic block, including unsupervised and semi-supervised. Our proposed solutions, analyzed with the Multi-Genre Broadcast 2015 (MGB) dataset, reported significant improvements (16% relative improvement) with respect to the baseline, also outperforming a supervised adaptation proposal with low resources (9% relative improvement). Furthermore, our proposed unsupervised adaptation is totally compatible with a supervised one. The joint use of both adaptation techniques (supervised and unsupervised) shows a 13% relative improvement with respect to only considering the supervised adaptation.
A fusion optimization algorithm of network element layout for indoor positioning
Authors: Yu Xiao-min , Wang Hui-qiang , Lv Hong-wu , Liu Xiu-bing , Wu Jin-qiu
Published: December 2019

The indoor scene has the characteristics of complexity and Non-Line of Sight (NLOS). Therefore, in the application of cellular network positioning, the layout of the base station has a significant influence on the positioning accuracy. In three-dimensional indoor positioning, the layout of the base station only focuses on the network capacity and the quality of positioning signal. At present, the influence of the coverage and positioning accuracy has not been considered. Therefore, a network element layout optimization algorithm based on improved Adaptive Simulated Annealing and Genetic Algorithm (ASA-GA) is proposed in this paper. Firstly, a three-dimensional positioning signal coverage model and a base station layout model are established. Then, the ASA-GA algorithm is proposed for optimizing the base station layout scheme. Experimental results show that the proposed ASA-GA algorithm has a faster convergence speed, which is 16.7% higher than the AG-AC (Adaptive Genetic Combining Ant Colony) algorithm. It takes about 25 generations to achieve full coverage. At the same time, the proposed algorithm has better coverage capability. After optimization of the layout of the network element, the effective coverage rate is increased from 89.77 to 100% and the average location error decreased from 2.874 to 0.983 m, which is about 16% lower than the AG-AC algorithm and 22% lower than the AGA (Adaptive Genetic Algorithm) algorithm.
Magnetic resonance spectroscopy across chronic pain disorders: a systematic review protocol synthesising anatomical and metabolite findings in chronic pain patients
Authors: Levins Kirk J. , Drago Thomas , Roman Elena , Martin Anna , King Roisin , Murphy Paul , Gallagher Hugh , Barry Denis , O’Hanlon Erik , Roddy Darren William
Published: December 2019

Background

Chronic pain is pain greater than 3 months duration that may result from disease, trauma, surgery, or unknown origin. The overlap between the psychological, behavioural, and management aspects of pain suggest that limbic brain neurochemistry plays a role in chronic pain pathology. Proton magnetic resonance spectroscopy (1H-MRS) can evaluate in vivo brain metabolites including creatine,N-acetylaspartate, myo-inositol, choline, glutamate, glutamine, and gamma-aminobutyric acid in chronic pain; however, a comprehensive systemic review of metabolite expression patterns across all brain areas has yet to be performed.

Methods and analysis

Online databases including PubMed/MEDLINE, Google Scholar, EMBASE, the Cochrane Library, OVID, and PsycINFO will be searched for articles relating to1H-MRS and chronic pain. Study inclusion criteria will include ages of between 18 and 65 years with a definite diagnosis of chronic pain, no comorbidities, clearly stated brain volumes of interest, and imaging protocols, with comparisons to healthy controls. Two reviewers will extract data relating to volumes of interest, metabolites, study participant demographics, diagnostic method and pain scores, treatments and duration of treatment, scanner information,1H-MRS acquisition protocols, and spectral processing software. Where possible, volumes of interest will be reassigned as regions of interest consistent with known regional anatomical and functional properties to increase the power and relevance of the analysis. Statistical analyses will then be conducted using STATA. A central common pathway may exist for chronic pain due to the behavioural manifestations and management similarities between its different types. The goal of this systemic review is to generate a comprehensive neurochemical theory of chronic pain in different brain compartments.

Systematic review registration

This study is registered with PROSPEROCRD42018112640.
Does decision-making style predict managers’ entrepreneurial intentions?
Authors: Krasniqi Besnik A. , Berisha Gentrit , Pula Justina Shiroka
Published: December 2019

The purpose of this paper is to investigate whether the way managers make decisions (their decision-making style—DMS) predicts their entrepreneurial intentions (EI), a research subject that has been largely ignored in the literature. Developing an understanding of entrepreneurial intention factors that attract managers to entrepreneurship is indispensable for organizations. A sample of 230 managers of companies based in Kosovo was asked to take the entrepreneurial intention questionnaire and the General Decision-Making Style (GDMS) questionnaire. Bridging two strands of literature on decision-making and entrepreneurial intention and using the Structural Equation Model (SEM), it is concluded that spontaneous and intuitive styles predict managers’ entrepreneurial intentions. Considering the limitations of this single-country study, the implications for theory and policy are discussed.
Evidence of uptake of different pollutants in plants harvested from soil treated and fertilized with organic materials as source of soil nutrients from developing countries
Authors: Olowoyo J. O. , Mugivhisa L. L.
Published: December 2019

The use of organic materials as soil nutrients to improve agricultural production is well documented. However, these organic materials may contain toxic pollutants that may bio-accumulate in plant tissues and eventually be consumed by humans. There is a misconception about the use of organic materials (sludge, urine, human waste and urban waste) in agriculture and organic farming. The review work examined the sources and uses of organic material in agriculture from developing countries and the dangers posed by the use of polluted organic materials in agriculture. The review examined through literature the availability and uptake of pollutants in crops that are cultivated from farming activities using organic materials. The review established the possibility of uptake of pollutants from treated waste materials that are used for farming. Some of the pollutants that can be bio-accumulated by plants when cultivated on soil containing these pollutants were documented. The review concluded by establishing the need to create awareness on the possible health risks associated with the use of organic materials if the materials used were polluted. The review also highlighted the importance of educating peasant farmers on the dangers associated with collecting waste materials from untreated sources.
Numerical simulations to explain the coseismic electromagnetic signals: a case study for a M5.4 aftershock of the 2016 Kumamoto earthquake
Authors: Sun Yao-Chong , Uyeshima Makoto , Ren Hengxin , Huang Qinghua , Aizawa Koki , Tsukamoto Kaori , Kanda Wataru , Seki Kaori , Kishita Takahiro , Ohminato Takao , Watanabe Atsushi , Ran Jiangjun , Chen Xiaofei
Published: December 2019

Coseismic electromagnetic (EM) signals that appear from the P arrival were observed in a volcanic area during the 2016 Kumamoto earthquake. In this study, we conduct numerical simulations to explain the coseismic EM signals observed for aM5.4 aftershock of the earthquake. Initially, we adopt a water-saturated half-space model, and its simulation result for a receiver with a depth of 0.1 m suggests that the magnetic signals do not show up at the arrivals of P, refracted SV–P and Rayleigh waves because the evanescent EM waves just counterbalance the localized magnetic signals that accompany P, refracted SV–P and Rayleigh waves. Then, we conduct numerical simulations on a seven-layer half-space model in which the second layer corresponds to an aquifer analogy and the six other layers refer to air-saturated porous media. When only the electrokinetic effect is considered, the simulated coseismic magnetic signals still appear from the S arrival. The combination of electrokinetic effect and surface-charge assumption is also tested. We find that signals before the S arrival are missing on the transverse seismic, transverse electric, radial magnetic and vertical magnetic components, although the situation on horizontal magnetic components is improved to an extent. Then, we introduce an artificial scattering effect into our numerical simulations given that the scattering effect should exist in the volcanic area. New numerical result shows good agreement with the observation result on the signal appearance time. Hence, the combination of electrokinetic and scattering effects is a plausible explanation of coseismic EM signals. Further investigations indicate that coseismic electric and/or magnetic signals are more sensitive to the scattering effect and the aquifer thickness than seismic signals.