bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety of Gastrostomy Tube Placement in Patients with Advanced Amyotrophic Lateral Sclerosis With Noninvasive Ventilation
Authors: Kim Eun Young , Kang Seong Woong , Suh Mi Ri , Jung Jiho , Park Jihyun , Choi Won Ah
Published: September 2020

Background

In patients with amyotrophic lateral sclerosis (ALS), bulbar muscle dysfunction can occur, which eventually requires the initiation of enteral tube feeding. However, there is no consensus on the optimal timing for the gastrostomy or the proper ventilator support method during the procedure. We aimed to investigate the safe range of gastrostomy according to respiratory support status and forced vital capacity (FVC) % of predicted values classification and to compare the safety of noninvasive and invasive mechanical ventilation during the procedure in ALS patients with FVC < 30% of predicted.

Methods

A total of 477 patients diagnosed with ALS at our institution from January 1, 2009, to December 31, 2018, were evaluated, and 105 patients were enrolled in this study. All medical records covering ventilation status and complications within 6 months to 1 year after the initial gastrostomy were gathered and reviewed.

Results

The gastrostomy procedure was considered safe regardless of FVC status or modality of respiratory support. There were complications related to the gastrostomy procedure in 6 of 105 patients and all were managed through conservative care. The incidence of complications, including respiratory ones, for noninvasive and invasive positive pressure ventilation was 5.5% and 9.6%, respectively, which were not statistically significantly different (P = .294).

Conclusion

The procedure and tube placement of a gastrostomy can be safely performed in ALS patients with minimal FVC regardless of ventilation invasiveness. We suggest that there should be a new standard for FVC % of predicted to facilitate performing gastrostomy in ALS patients.
Analysis of the active components and metabolites of Taohong Siwu decoction by using ultra high performance liquid chromatography quadrupole time‐of‐flight mass spectrometry
Authors: Duan Xianchun , Pan Lingyu , Peng Daiyin , Bao Qiuyu , Xiao Ling , Zhou An , Wu Huan , Peng Can , Chen Weidong
Published: September 2020

Taohong Siwu Decoction is a classic Chinese medicine prescription for treatment of cerebral ischemia and gynecological diseases. However, the active ingredients of Taohong Siwu Decoction have not been identified. In this study, a ultra performance liquid chromatography quadrupole time‐of‐flight mass system was used to analyze the active components and metabolites of Taohong Siwu Decoction absorbed into the blood and the brain. A total of 39 active compounds and 90 metabolites were identified in the blood and brain by comparing retention times, accurate masses, fragmentation patterns, and literature data. The results showed that flavonoids (Carthamus tinctorius L), aromatic organic acids, and benzoquinones (Angelica sinensis (Oliv.) Diels and Ligusticumchuanxiong hort) were prominent active ingredients in Taohong Siwu Decoction. Furthermore, hydrolysis, glucuronidation, and sulfation were identified as the main metabolic pathways of Taohong Siwu Decoction in vivo. This was the first study to characterize the active components and metabolites of Taohong Siwu Decoction in the blood and brain using ultra performance liquid chromatography quadrupole time‐of‐flight mass.
Velocity Vector Imaging to Assess Longitudinal Wall Motion of Adult Carotid Arteries
Authors: Gao Jing , Lee Juhyun , Phan Andrew , Fowlkes J. Brian
Published: September 2020

Objective

We aimed to assess longitudinal wall motion of the common carotid artery (CCA) using velocity vector imaging (VVI).

Methods

From October 2018 to July 2019, we prospectively performed VVI of 204 CCAs (102 adult volunteers, 57 men, 45 women) in young (n = 40, 20–44 y), mid‐age (n = 30, 45–64 y), and senior (n = 32, ≥65 y) groups. VVI parameters of CCA included longitudinal motion pattern, motion parameters (strain, strain rate, displacement), and time‐to‐peak motion parameters (time‐to‐peak strain, time‐to‐peak strain rate, time‐to‐peak displacement). Statistical analyses included one‐way ANOVA post‐hoc testing to examine the difference in VVI parameters among the 3 age groups and in paired groups; unpaired t tests to examine the difference in VVI parameters between CCAs with and without atherosclerotic plaque, between hypertensive and normotensive subjects without atherosclerotic plaque; linear regression to analyze correlations of VVI parameters to age, carotid intima‐media thickness; and intraclass correlation coefficient to test inter‐ and intra‐observer reliability in performing VVI of the CCA.

Results

Differences in VVI parameters and patterns among the 3 age groups, between hypertensive and normotensive, and CCAs with and without plaque were significant (p < .01). CCA motion‐ and time‐to‐peak motion parameters were correlated to age (R2 = 0.63–0.56) and carotid intima‐media thickness (R2 = 0.29–0.22). CCA wall motion dyssynchrony was remarkable in seniors. The repeatability and reproducibility for performing carotid artery VVI were good (intraclass correlation coefficient > 0.85).

Conclusions

VVI is feasible to assess changes in longitudinal CCA wall mechanical properties and synchrony with aging, atherosclerosis, and hypertension.
Factors governing soil water repellency under tillage management: The role of pore structure and hydrophobic substances
Authors: Li Shengping , Lu Jinjing , Liang Guopeng , Wu Xueping , Zhang Mengni , Plougonven Erwan , Wang Yunfei , Gao Lili , Abdelrhman Ahmed Ali , Song Xiaojun , Liu Xiaotong , Degré Aurore
Published: September 2020

Soil water repellency (SWR) has significant effects on soil degradation by changing some soil processes (e.g., carbon sequestration and soil erosion). Understanding the influence factors of SWR under conservation agriculture are playing a vital role in the sustainable development for improving soil quality. However, how soil pore structure influence on SWR remains unclear. We aim to assess the impact of hydrophobic substances and pore structure on SWR. Here we conducted two long‐term experimental fields with three treatments: conventional tillage (CT), reduced tillage (RT), and no‐tillage (NT). X‐ray tomography and the sorptivity method were used to measure soil pore structure and SWR, respectively. We found that soil organic carbon (SOC) and microbial biomass carbon (MBC) were higher in RT and NT treatments than in CT. MBC had significant influences on soil water sorptivity (Sw) and water repellency index (RI; p < 0.001), whereas SOC had no influence on Sw (p > 0.05). MBC also showed a closer relationship with SWR than SOC in redundancy analysis. The RT and NT increased the porosity of 55–165 μm that had a positive relationship with ethanol sorptivity and RI (p < 0.05). Ethanol sorptivity increased with an increase in soil pore porosity and connectivity under RT and NT treatments. However, increasing the pore surface area could decrease Sw due to enhance contact area between hydrophobic substances and soil water. Overall, the RT and NT treatments increased the water repellency index, which was a result of the interactions between pore structure and hydrophobic substances.
Data‐driven discovery of probable Alzheimer's disease and related dementia subphenotypes using electronic health records
Authors: Xu Jie , Wang Fei , Xu Zhenxing , Adekkanattu Prakash , Brandt Pascal , Jiang Guoqian , Kiefer Richard C. , Luo Yuan , Mao Chengsheng , Pacheco Jennifer A. , Rasmussen Luke V. , Zhang Yiye , Isaacson Richard , Pathak Jyotishman
Published: September 2020

Introduction

We sought to assess longitudinal electronic health records (EHRs) using machine learning (ML) methods to computationally derive probable Alzheimer's Disease (AD) and related dementia subphenotypes.

Methods

A retrospective analysis of EHR data from a cohort of 7587 patients seen at a large, multi‐specialty urban academic medical center in New York was conducted. Subphenotypes were derived using hierarchical clustering from 792 probable AD patients (cases) who had received at least one diagnosis of AD using their clinical data. The other 6795 patients, labeled as controls, were matched on age and gender with the cases and randomly selected in the ratio of 9:1. Prediction models with multiple ML algorithms were trained on this cohort using 5‐fold cross‐validation. XGBoost was used to rank the variable importance.

Results

Four subphenotypes were computationally derived. Subphenotype A (n = 273; 28.2%) had more patients with cardiovascular diseases; subphenotype B (n = 221; 27.9%) had more patients with mental health illnesses, such as depression and anxiety; patients in subphenotype C (n = 183; 23.1%) were overall older (mean (SD) age, 79.5 (5.4) years) and had the most comorbidities including diabetes, cardiovascular diseases, and mental health disorders; and subphenotype D (n = 115; 14.5%) included patients who took anti‐dementia drugs and had sensory problems, such as deafness and hearing impairment.

The 0‐year prediction model for AD risk achieved an area under the receiver operating curve (AUC) of 0.764 (SD: 0.02); the 6‐month model, 0.751 (SD: 0.02); the 1‐year model, 0.752 (SD: 0.02); the 2‐year model, 0.749 (SD: 0.03); and the 3‐year model, 0.735 (SD: 0.03), respectively. Based on variable importance, the top‐ranked comorbidities included depression, stroke/transient ischemic attack, hypertension, anxiety, mobility impairments, and atrial fibrillation. The top‐ranked medications included anti‐dementia drugs, antipsychotics, antiepileptics, and antidepressants.

Conclusions

Four subphenotypes were computationally derived that correlated with cardiovascular diseases and mental health illnesses. ML algorithms based on patient demographics, diagnosis, and treatment demonstrated promising results in predicting the risk of developing AD at different time points across an individual's lifespan.
Artificial Muscles from Hybrid Carbon Nanotube‐Polypyrrole‐Coated Twisted and Coiled Yarns
Authors: Aziz Shazed , Martinez Jose G. , Foroughi Javad , Spinks Geoffrey M. , Jager Edwin W. H.
Published: September 2020

Electrochemically or electrothermally driven twisted/coiled carbon nanotube (CNT) yarn actuators are interesting artificial muscles for wearables as they can sustain high stress. However, due to high fabrication costs, these yarns have limited their application in smart textiles. An alternative approach is to use off‐the‐shelf yarns and coat them with conductive polymers that deliver high actuation properties. Here, novel hybrid textile yarns are demonstrated that combine CNT and an electroactive polypyrrole coating to provide both high strength and good actuation properties. CNT‐coated polyester yarns are twisted and coiled and subjected to electrochemical coating of polypyrrole to obtain the hierarchical soft actuators. When twisted without coiling, the polypyrrole‐coated yarns produce fully reversible 25° mm‐1 rotation, 8.3× higher than the non‐reversible rotation from twisted CNT‐coated yarns in a three‐electrode electrochemical system operated between +0.4 and –1.0 V (vs Ag/AgCl). The coiled yarns generate fully reversible 10° mm‐1 rotation and 0.22% contraction strain, 2.75× higher than coiled CNT‐coated yarns, when operated within the same potential window. The twisted and coiled yarns exhibit high tensile strength with excellent abrasion resistance in wet and dry shearing conditions that can match the requirements for using them as soft actuators in wearables and textile exoskeletons.
Modelling t(8;21) acute myeloid leukaemia ‐ What have we learned?
Authors: Chin Paulynn Suyin , Bonifer Constanze
Published: September 2020

Acute myeloid leukaemia (AML) is a heterogeneous haematopoietic malignancy caused by recurrent mutations in haematopoietic stem and progenitor cells that affect both the epigenetic regulatory machinery and signalling molecules. The t(8;21) or RUNX1‐RUNX1T1 translocation generates the RUNX1‐ETO chimeric transcription factor which primes haematopoietic stem cells for further oncogenic mutational events that in their sum cause overt disease. Significant progress has been made in generating both in vitro and in vivo model systems to recapitulate t(8;21) AML which are crucial for the understanding of the biology of the disease and the development of effective treatment. This review provides a comprehensive overview of the in vivo and in vitro model systems that were developed to gain insights into the molecular mechanisms of RUNX1‐ETO oncogenic activity and their contribution to the advancement of knowledge in the t(8;21) AML field. Such models include transgenic mice, patient‐derived xenografts, RUNX1‐ETO transduced human progenitor cells, cell lines and human embryonic stem cell model systems, making the t(8;21) as one of the well‐characterized sub‐type of AML at the molecular level.
Serious Transport Accidents in Tourette Syndrome or Chronic Tic Disorder
Authors: Mataix‐Cols David , Brander Gustaf , Chang Zheng , Larsson Henrik , D'Onofrio Brian M. , Lichtenstein Paul , Sidorchuk Anna , Fernández de la Cruz Lorena
Published: September 2020

Background

It is unknown whether individuals with tic disorders are at increased risk for serious transport accidents.

Objectives

The aim of this study was to investigate the risk for injuries or death caused by transport and motor vehicle accidents in individuals with Tourette syndrome or chronic tic disorder.

Methods

This population‐based, sibling‐controlled cohort study included all individuals aged ≥18 years living in Sweden between 1997 and 2013 (N = 6,127,290). A total of 3449 individuals had a registered diagnosis of Tourette syndrome or chronic tic disorder in the Swedish National Patient Register. We also identified 2191 families with full siblings discordant for tic disorders. Cox proportional hazards regression modeling was used to estimate the risk for injuries or deaths as a result of transport accidents in individuals with a lifetime diagnosis of Tourette syndrome or chronic tic disorder compared with unexposed individuals and siblings.

Results

Individuals with tic disorders had a higher risk for transport injuries or death compared with the general population (adjusted hazard ratio, 1.50 [95% confidence interval: 1.33–1.69]) and their unaffected siblings (adjusted hazard ratio, 1.41 [95% confidence interval: 1.18–1.68]). The risks were similar across sexes. The exclusion of most psychiatric comorbidities did not alter the magnitude of the estimates. However, the risks were no longer significant after exclusion of individuals with comorbid attention deficit hyperactivity disorder.

Conclusions

The marginally increased risk for serious transport accidents in tic disorders is mainly driven by attention deficit hyperactivity disorder comorbidity. Improved detection and management of attention deficit hyperactivity disorder symptoms in this patient group are warranted. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
A de novo heterozygous variant in the SON gene is associated with Zhu‐Tokita‐Takenouchi‐Kim syndrome
Authors: Yang Lianlian , Yang Fan
Published: September 2020

Background

Zhu‐Tokita‐Takenouchi‐Kim (ZTTK, OMIM# 617140) syndrome is a rare, autosomal dominant genetic disorder caused by heterozygous variants in the SON gene (OMIM#182465, GenBank#NC_000021.9). There are only 33 cases and 26 causative SON variants reported to date since the first report in 2015. Here, we report a new case of ZTTK syndrome and a de novo disease‐causing SON variant.

Methods

We conducted whole‐exome sequencing (WES) to obtain genetic data of the patient. The clinical and genetic data of the patient were analyzed.

Results

The clinical features of our patient were strikingly similar to previously reported cases. Notably, our patient had unique presentations, including a bridged palmar crease in the left hand and growth hormone deficiency. The c.5297del de novo variant in SON causes an amino change (p.Ser1766Leufs*7).

Conclusion

Our report expands the mutant spectrum of the SON gene and refines the genotype‐phenotype map of ZTTK syndrome. Our findings also highlighted the importance of WES for early diagnosis of ZTTK syndrome, which may improve diagnostic procedures for affected individuals.
Improved accuracy and convergence analysis of finite volume methods for particle fragmentation models
Authors: Saha Jitraj , Bück Andreas
Published: September 2020

In this work, two new number‐ and volume‐consistent finite volume methods for the numerical solution of binary and multifragmentation problems are introduced. The new number‐consistency is achieved by introducing a single weight function. Several benchmark problems of different complexity are solved to assess the accuracy. Mathematical convergence analysis suggests that both of the new methods are numerically second order convergent with respect to the grid size on uniform and nonuniform meshes.
A Bayesian control chart based on the beta distribution for monitoring the two‐dimensional gamma index pass rate in the context of patient‐specific quality assurance
Authors: Tiplica Teodor , Dufreneix Stéphane , Legrand Christophe
Published: September 2020

Purpose

In the context of quality assurance in intensity modulated radiation therapy (IMRT), the aim of this work was two‐fold: (a) to show that the beta distribution characterizes the two‐dimensional gamma index pass rate (GIPR), and that the quantiles of the distribution should be used in order to compute the control limit (CL) for the detection of abnormally low GIPR, and (b) to introduce a Bayesian control chart that allows calculation of CLs from the first measurement.

Methods

In order to enable monitoring of the GIPR from the first measurement, we developed a Bayesian control chart based on the beta distribution, elaborated according to the following two steps: (a) an iterative bayesian inference approach without any prior information on the GIPR distribution was used at the start of monitoring and the CL was progressively updated; and (b) when sufficient in‐control arcs had been recorded and the estimators of the parameters of the beta distribution were sufficiently accurate, the CL of the chart was fixed to a constant value corresponding to the quantile of the beta distribution. The clinical utility of this approach is illustrated through a real data case study: monitoring the GIPR of patients treated with a moving gantry IMRT technique RapidArcTM on a Novalis TrueBeam STx (Varian Medical Systems) linear accelerator equipped with an aS1200 electronic portal imager device.

Results

We showed that some commonly used distributions for monitoring GIPR in the literature, such as normal or logarithm transformation, are not appropriate. We compared the CLs of those solutions with the CL of our chart based on the BD (CL = 95.14%). The comparison revealed that the CL for the normal law (CL = 97.62%) generated too many false positives, and that the CL of the Logarithm transformation (CL = 83.74%) could fail to efficiently detect (i.e., sufficiently early on or faster) changes in the process.

Conclusions

Successful GIPR monitoring requires careful and rigorous application of well‐established statistical concepts in the field of statistical process control. In this paper, we stress the importance of carefully analyzing the distribution of the monitored characteristic that is plotted on the control chart. We propose a Bayesian control chart that can be viewed as a practical solution for early implementation of GIPR monitoring, starting from the first arc. We demonstrate that beta distribution is a better method for characterizing the GIPR, and thus, the use of this approach is expected to improve patient‐specific quality assurance plans in radiotherapy.
Frequency‐stabilized chemical exchange saturation transfer imaging with real‐time free‐induction‐decay readout
Authors: Liu Ruibin , Zhang Hongxi , Qian Yue , Hsu Yi‐Cheng , Fu Caixia , Sun Yi , Wu Dan , Zhang Yi
Published: September 2020

Purpose

To correct the temporal B0 drift in chemical exchange saturation transfer (CEST) imaging in real‐time with extra free‐induction‐decay (FID) readout.

Theory and Methods

The frequency stabilization module of the recently proposed frequency‐stabilized CEST (FS‐CEST) sequence was further simplified by replacing the original three k‐space lines of gradient‐echo (GRE) readout with a single k‐space line of FID readout. The B0 drift was quantified using the phase difference between the odd and even parts of the FID signal in the frequency stabilization module and then used to update the B0 frequency in the succeeding modules. The proposed FS‐CEST sequence with FID readout (FID FS‐CEST) was validated in phantoms and 16 human subjects on cross‐vendor scanners.

Results

In the Siemens experiments, the FID FS‐CEST sequence successfully corrected the user‐induced B0 drift, generating consistent amide proton transfer‐weighted (APTw) images and magnetization transfer ratio asymmetry (MTRasym) spectra with those from the non‐frequency‐stabilized CEST (NFS‐CEST) sequence without B0 drift. In the Philips experiments, the FID FS‐CEST sequence produced more stable APTw images and MTRasym spectra than the NFS‐CEST sequence in the presence of practical B0 drift. Quantitatively, the SD of the APTw signal values in the deep gray matter from 15 subjects was 0.26% for the FID FS‐CEST sequence compared to 1.03% for the NFS‐CEST sequences, with the fluctuations reduced by nearly three‐quarters.

Conclusions

The proposed FS‐CEST sequence with FID readout can effectively correct the temporal B0 drift on cross‐vendor scanners.
Density-Dependent Changes in Grass Carp Growth and Mortality in Long-Term Aquatic Plant Management
Authors: Caves Stradder , Baumann Jessica R. , Stich Daniel S.
Published: September 2020

The Grass Carp Ctenopharyngodon idella is an herbivorous fish that has been stocked throughout the United States for aquatic plant control, commonly to manage hydrilla Hydrilla verticillata. Triploid Grass Carp were purported to have a mean life span of about 11 years based on otolith-assigned ages and mortality estimates for fish associated with large stocking efforts through which aquatic plants were eliminated. Recent studies in aquatic systems where preferred foods were not eliminated have found that Grass Carp may live up to 30 years or more, but information about growth and mortality is lacking. About 130,000 Grass Carp have been stocked since 1995 to manage hydrilla in combination with fluridone application in Lake Gaston, Virginia–North Carolina, USA. Hydrilla coverage peaked at about 1,300 ha in 2003 and was reduced to about 130 ha by 2014. Since 2006, a total of 419 Grass Carp have been collected for age and growth analysis. A Bayesian approach was used to estimate von Bertalanffy growth function parameters that incorporated the effects of a linear trend in year, hydrilla abundance, or Grass Carp density and to assess population changes. Fish that were stocked in 1995 persisted through 2017. Mean maximum length (L∞) of Grass Carp decreased by about 200 mm with an increasing number of Grass Carp per hectare of hydrilla, and fish reached maximum size earlier in life. Indirect mortality estimates derived from growth parameters increased with Grass Carp density. Because preferred food availability affects mortality rates, stocking numbers should vary accordingly to maximize the effectiveness of hydrilla control programs.
Preconditioned tensor splitting AOR iterative methods for ℋ‐tensor equations
Authors: Wang Xuezhong , Che Maolin , Wei Yimin
Published: September 2020

Based on the weak regular splitting of tensors, preconditioned technology has shown great advantages in solving tensor equations with nonsingular (strong) ‐tensors. In this article, we introduce H‐splitting and H‐compatible splitting and investigate the relationship between these different splittings and their convergence. Meanwhile, we also consider a preconditioned AOR iterative method for solving tensor equations with nonsingular ‐tensors. We prove its convergence and give a comparison result on the spectral radius of the iteration tensor for the case when is a nonsingular ‐tensor. Numerical examples are also given to illustrate our methods.
What constitutes feeling safe at home? A qualitative interview study with frail older people receiving home care
Authors: Silverglow Anastasia , Lidèn Eva , Berglund Heléne , Johansson Lena , Wijk Helle
Published: September 2020

Aim

To highlight experiences of what constitutes feeling safe at home among frail older people receiving home care.

Design

Qualitative descriptive study.

Methods

The sample consists of 12 individual recorded interviews with frail older people in their homes. Interviews were transcribed verbatim and analysed using qualitative content analysis. The data collection was performed in spring 2018.

Results

The analysis resulted in three categories: “Having a feeling of ‘at‐homeness’” describes the older people's surrounding environment and their efforts to maintain independence; “being able to influence” describes the importance for older people to shape their care by being in control and having an opportunity for self‐determination in the context of home care; and “being able to trust staff” relates to expecting staff's knowledge and skills and to appreciating the staff's ability to create positive relations.
Nurses' knowledge and practices of physical restraints in intensive care units: An observational study
Authors: Almomani Maysa H. , Khater Wejdan A. , Qasem Baha'a Aldin Abdel‐Latif , Joseph Rachel A.
Published: September 2020

Aim

To investigate the knowledge and practice of physical restraints (PR) among Jordanian intensive care unit (ICU) nurses.

Design

A descriptive, observational design was used.

Methods

A convenience sampling was used to recruit participants. We examined the knowledge of PR in 301 nurses (knowledge check) and the real‐time practice of PR in 81 nurses (direct observation) in ICU. A knowledge questionnaire was used to collect data on knowledge about PR use, and data on their practice of PR were observed and documented using an observation checklist.

Results

The mean scores of nurses' knowledge and practices were 61.5 (SD = 12.1) and 57.4 (SD = 9.7), respectively. More than half of nurses had poor knowledge of PR use and incorrect practice of implementing PR (51.5% and 60.5%, respectively). Results indicated a positive correlation between nurses' knowledge and their use of PR.
Onset of Workplace Bullying and Risk of Weight Gain: A Multicohort Longitudinal Study
Authors: Xu Tianwei , Magnusson Hanson Linda L. , Clark Alice J. , Ersbøll Annette K. , Westerlund Hugo , Madsen Ida E. H. , Rugulies Reiner , Pentti Jaana , Stenholm Sari , Vahtera Jussi , Sørensen Jeppe K. , Nordentoft Mads , Westendorp Rudi G. J. , Hansen Åse M. , Oksanen Tuula , Virtanen Marianna , Kivimäki Mika , Rod Naja H.
Published: September 2020

Objective

This study aimed to examine the onset of workplace bullying as a risk factor for BMI increase.

Methods

Repeated biennial survey data from three Nordic cohort studies were used, totaling 46,148 participants (67,337 participant observations) aged between 18 and 65 who did not have obesity and who were not bullied at the baseline. Multinomial logistic regression was applied for the analysis under the framework of generalized estimating equations.

Results

Five percent reported onset of workplace bullying within 2 years from the baseline. In confounder‐adjusted models, onset of workplace bullying was associated with a higher risk of weight gain of ≥ 1 BMI unit (odds ratio = 1.09; 95% CI: 1.01‐1.19) and of ≥ 2.5 BMI units (odds ratio = 1.24; 95% CI: 1.06‐1.45). A dose‐response pattern was observed, and those exposed to workplace bullying more frequently showed a higher risk (Ptrend = 0.04). The association was robust to adjustments, restrictions, stratifications, and use of relative/absolute scales for BMI change.

Conclusions

Participants with exposure to the onset of workplace bullying were more likely to gain weight, a possible pathway linking workplace bullying to increased long‐term risk of type 2 diabetes.
Optimizing autocatalysis with uncertainty by derivative‐free estimators
Authors: Rohman Fakhrony S. , Sata Suhairi A. , Othman Mohd Roslee , Aziz Norashid
Published: September 2020

A derivative‐free estimator was introduced to alleviate the drawbacks of the conventional Kalman filter when performing nonlinear analyses under different circumstances. In this work, the scaled Unscented Kalman Filter, Divided Difference Kalman filter, and Cubature Kalman filter (CKF) were selected to investigate the effectiveness of these filters in predicting the states of a complex semi‐batch reaction between propionic anhydride and 2‐butanol. The estimator's performance was evaluated under four different case studies, that is, under normal condition, under poor estimator initialization, under disturbances, and under parameter uncertainty. Results from the study show that CKF was the best option for an online dynamic optimization because of its highest degree of accuracy and stability under the normal and noisy conditions. Under normal condition, CKF yielded the lowest root mean square error of 0.61 × 10−2. Under uncertain initial condition, disturbance and parameter uncertainty, the lowest error of 1.83 × 10−2, 1.04 × 10−2, and 0.81 × 10−2 were obtained, respectively.
A Pilot Study of Checkpoint Inhibitors in Solid Organ Transplant Recipients with Metastatic Cutaneous Squamous Cell Carcinoma
Authors: Tsung Irene , Worden Francis P. , Fontana Robert J.
Published: September 2020

Background

Immune checkpoint inhibitors (ICIs) are increasingly used in various solid organ malignancies. However, there are limited data regarding their safety and efficacy in solid organ transplant (SOT) recipients. The aim of this study was to review our experience with ICIs in SOT recipients with advanced head and neck cutaneous squamous cell carcinoma (cSCC).

Methods

A retrospective review of ICIs used in SOT recipients from April 2011 to September 2019 was undertaken. Patient clinical and demographic features, ICI regimen, immunosuppression, treatment efficacy, and adverse events were reviewed.

Results

The seven SOT recipients (four kidney, two liver, one lung) were diagnosed with metastatic head and neck cSCC. All had undergone prior locoregional surgery and adjuvant radiation therapy. At a median of 10.8 years (range, 6.6–18.1) post-transplant, six were treated with cemiplimab and one with pembrolizumab after minimizing calcineurin inhibitors (CNIs) or conversion of CNI to mammalian target of rapamycin (mTOR) inhibitors. During a median follow-up of 7.1 months, overall tumor response rate was 57.1% with one complete responder and three partial responders. Four patients died at a median of 135 days after starting ICI with two dying from tumor progression and two dying from other causes. Regarding adverse events, one lung transplant recipient developed severe pneumonitis that resolved with high-dose steroids, and one renal transplant patient developed progressive renal injury and died of unrelated causes. The three patients who received prophylactic prednisone all responded to cemiplimab with preserved allograft function and no adverse events.

Conclusion

Our data suggest that minimization of CNI and conversion of CNI to mTOR inhibitors along with judicious use of prophylactic steroids may allow for the safe use of ICIs in SOT recipients with advanced cSCC. Short-term efficacy appears promising, but prospective studies with further follow-up and a standardized protocol for prophylactic steroids are needed.

Implications for Practice

Solid organ transplant (SOT) recipients are at increased risk of developing malignancy because of long-term post-transplant immunosuppression. Although immune checkpoint inhibitors (ICIs) are increasingly shown to be successful in treating multiple types of cancer, SOT recipients have been excluded from clinical trials because of concerns regarding potential allograft rejection. This pilot study provides evidence that ICIs along with prophylactic steroids may be a safe and efficacious treatment option for selected SOT recipients with advanced cutaneous squamous cell carcinoma. However, further prospective studies using ICIs in this high-risk patient population are needed.
D-Dimer Enhances Risk-Targeted Thromboprophylaxis in Ambulatory Patients with Cancer
Authors: Kumar Vaibhav , Shaw Joseph R. , Key Nigel S. , Ilich Anton , Mallick Ranjeeta , Wells Philip S. , Carrier Marc
Published: September 2020

Background

Thromboprophylaxis for ambulatory patients with cancer is effective, although uncertainties remain on who should be targeted. Using D-dimer values from individuals enrolled to the AVERT trial, we sought to identify and validate a more efficient venous thromboembolism (VTE) risk threshold for thromboprophylaxis.

Materials and Methods

The AVERT trial compared thromboprophylaxis with apixaban with placebo among patients with cancer with a Khorana Risk Score ≥2. The D-dimer measured at randomization was used to calculate an individualized 6-month VTE risk using the validated CATScore. A modified intention-to-treat analysis was used to assess efficacy (VTE) and safety (major and overall bleeding) in the (a) complete cohort and (b) ≥8% and < 8% 6-month VTE risk thresholds.

Results

Five hundred seventy-four patients were randomized in the AVERT trial; 466 (81%) with baseline D-dimer were included in the study. Two hundred thirty-seven subjects received apixaban; 229 received placebo. In the complete cohort, there were 13 (5.5%) VTE events in the apixaban arm compared with 26 (11.4%) events in the placebo arm (adjusted hazard ratio [aHR] 0.49 [0.25–0.95], p < .05). Number needed to treat (NNT) to prevent one VTE = 17. Eighty-two (35%) and 72 (31%) patients in the apixaban and placebo arms, respectively, had a 6-month VTE risk ≥8%. In this subgroup, 7 (8.4%) VTE events occurred with apixaban and 19 (26.3%) events with placebo (aHR 0.33 [0.14-0.81], p < .05), NNT = 6. Individuals with a VTE risk <8% derived no benefit from apixaban thromboprophylaxis (aHR 0.89 [0.30–2.65), p = .84). Increased rates of overall bleeding were observed with apixaban in both the complete (aHR 2.11 [1.09–4.09], p < .05) and ≥ 8% predicted risk cohorts (aHR 2.87 [0.91–9.13], p = .07).

Conclusion

A 6-month VTE risk threshold of ≥8% increases the efficiency of risk-targeted thromboprophylaxis in ambulatory patients with cancer.

Implications for Practice

Ambulatory patients with cancer receiving chemotherapy have an increased risk of venous thromboembolism (VTE). A Khorana Risk Score (KRS) ≥2 is currently the suggested threshold for thromboprophylaxis. Using baseline D-dimer values from individuals enrolled to the AVERT trial, this retrospective validation study identifies a 6-month VTE risk of ≥8% as a more efficient threshold for thromboprophylaxis. At this threshold, the number needed to treat to prevent one VTE is 6, compared with 17 when using a KRS ≥2. Conversely, individuals with a predicted risk of <8% derive no clinical benefit from thromboprophylaxis. Future prospective studies should validate this threshold for outpatient thromboprophylaxis.
Personality traits and entrepreneurial intention: The mediating role of risk aversion
Authors: Ahmed Malik Aftab , Khattak Muhammad Sualeh , Anwar Muhammad
Published: September 2020

The aim of this paper is to investigate the influence of big five personality traits on entrepreneurial intentions with the mediating role of risk aversion. A structured questionnaire was used and collected data from 274 Pakistani students (university level). The hypotheses were tested through structural equation modeling by using AMOS. The findings display that the personality trait “conscientiousness” has a significant positive influence on entrepreneurial intentions while the traits, extroversion, openness to experience neuroticism, and agreeableness are not significantly influenced entrepreneurial intentions directly. Neuroticism, conscientiousness, and openness have a significant relationship with risk aversion while extroversion and agreeableness do not significantly influence risk aversion. There is a significant association between risk aversion and entrepreneurial intention. Risk aversion fully mediates the relationship of neuroticism and openness to experience with entrepreneurial intention while it partially mediates the path between consciousness and entrepreneurial intention. However, we found that risk aversion does not mediate the relationship between extroversion and agreeableness with entrepreneurial intention. The study suggests investors and policymakers to understand the behavior of students who are prominent future entrepreneurs and promote new start‐ups among students by providing various incentives (financial and nonfinancial). Other implications are stated.
Genomic analysis of low‐grade serous ovarian carcinoma to identify key drivers and therapeutic vulnerabilities
Authors: Cheasley Dane , Nigam Abhimanyu , Zethoven Magnus , Hunter Sally , Etemadmoghadam Dariush , Semple Timothy , Allan Prue , Carey Mark S , Fernandez Marta L , Dawson Amy , Köbel Martin , Huntsman David G , Le Page Cécile , Mes‐Masson Anne‐Marie , Provencher Diane , Hacker Neville , Gao Yunkai , Bowtell David , deFazio Anna , Gorringe Kylie L , Campbell Ian G
Published: September 2020

Low‐grade serous ovarian carcinoma (LGSOC) is associated with a poor response to existing chemotherapy, highlighting the need to perform comprehensive genomic analysis and identify new therapeutic vulnerabilities. The data presented here represent the largest genetic study of LGSOCs to date (n = 71), analysing 127 candidate genes derived from whole exome sequencing cohorts to generate mutation and copy‐number variation data. Additionally, immunohistochemistry was performed on our LGSOC cohort assessing oestrogen receptor, progesterone receptor, TP53, and CDKN2A status. Targeted sequencing identified 47% of cases with mutations in keyRAS/RAFpathway genes (KRAS,BRAF, andNRAS), as well as mutations in putative novel driver genes includingUSP9X(27%),MACF1(11%),ARID1A(9%),NF2(4%),DOT1L(6%), andASH1L(4%). Immunohistochemistry evaluation revealed frequent oestrogen/progesterone receptor positivity (85%), along with CDKN2A protein loss (10%) and CDKN2A protein overexpression (6%), which were linked to shorter disease outcomes. Indeed, 90% of LGSOC samples harboured at least one potentially actionable alteration, which in 19/71 (27%) cases were predictive of clinical benefit from a standard treatment, either in another cancer's indication or in LGSOC specifically. In addition, we validated ubiquitin‐specific protease 9X (USP9X), which is a chromosome X‐linked substrate‐specific deubiquitinase and tumour suppressor, as a relevant therapeutic target for LGSOC. Our comprehensive genomic study highlighted that there is an addiction to a limited number of unique ‘driver’ aberrations that could be translated into improved therapeutic paths. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Dexamethasone dosing for prevention of acute chemotherapy‐induced vomiting in pediatric patients: A systematic review
Authors: Patel Priya , Olteanu Ana , Cabral Sandra , Santesso Nancy , Robinson Paula D. , Dupuis L. Lee
Published: September 2020

A systematic review was undertaken to describe dexamethasone doses studied for chemotherapy‐induced vomiting (CIV) prophylaxis in pediatric patients and their effects on achieving complete acute CIV control. No dose‐finding studies were identified. However, 16 studies assessing pediatric patients who received dexamethasone were included and classified according to the emetogenicity of chemotherapy administered. Eight different total daily dexamethasone doses were administered to patients on day 1 of highly emetogenic chemotherapy: three in conjunction with aprepitant/fosaprepitant plus a 5HT3 antagonist and five in conjunction with a 5HT3 antagonist. Five different total daily dexamethasone doses were administered in conjunction with a 5HT3 antagonist to patients on day 1 of moderately emetogenic chemotherapy. Due to the heterogeneity of studies identified, meta‐analysis was not possible. The optimal dexamethasone dose to control acute CIV and to minimize harms in pediatric patients remains uncertain. This is a key area for future research.
Central nervous system lesions in Fanconi anemia: Experience from a research center for Fanconi anemia patients
Authors: Aksu Tekin , Gümrük Fatma , Bayhan Turan , Coşkun Çağrı , Oğuz Kader K. , Unal Sule
Published: September 2020

Background

Brain atrophy, abnormal pituitary morphology, corpus callosum, and posterior fossa abnormalities have been described in patients with Fanconi anemia (FA). We aimed to provide an overview of cranial neuroimaging findings and to evaluate the clinical implications in FA patients.

Procedure

Cranial magnetic resonance imaging (MRI) studies of 34 patients with FA were retrospectively evaluated, and patients’ clinical data were correlated with the imaging findings.

Results

The patients’ median age was 17.6 (range, 3.9‐28) years. At least one pathological brain imaging finding was demonstrated in 22 (65%) patients. These findings included corpus callosum abnormalities and other related supratentorial malformations in nine, pituitary abnormalities in eight, craniovertebral junction and posterior fossa abnormalities in eight, vascular lesions in six, and intracerebral calcifications in two patients. Among the 22 patients who had abnormal cranial MRI findings, six (27%) had mild to moderate intellectual disability (ID), three (14%) had epilepsy, one (5%) had mild hearing loss, and one patient (5%) had hemiplegia. Among these 34 patients, 14 (41%) were transfusion dependent. There was no significant difference between patients with congenital and acquired neuroimaging findings and patients with normal neuroimaging regarding transfusion dependency.

Conclusions

Acquired abnormalities in brain tissue, such as white matter intensity changes, white matter T2 hyperintense discrete foci, or infarcts along with congenital abnormalities, were identified in this study. Variable abnormal brain imaging findings in FA patients, although some were not associated with clinical neurological manifestations, suggest that brain imaging could be part of screening in FA.
Corticosteroid and Local Anesthetic Use Trends for Large Joint and Bursa Injections: Results of a Survey of Sports Medicine Physicians
Authors: Cushman Daniel M. , Teramoto Masaru , Asay Alexandra , Clements Nathan D. , McCormick Zachary L.
Published: September 2020

Background

Physician decision‐making surrounding choices for large joint and bursa injections is poorly defined, yet influences patient safety and treatment effectiveness.

Objective

To identify practice patterns and rationale related to injectate choices for large joint and bursal injections performed by physician members of the American Medical Society for Sports Medicine (AMSSM).

Design

An electronic survey was sent to 3400 members of the AMSSM. Demographic variables were collected: primary specialty (residency), training location, practice location, years of clinical experience, current practice type, and rationale for choosing an injectate.

Participants

A total of 674 physicians responded (minimum response rate of 20%).

Intervention

Not applicable.

Main Outcome Measures

Outcomes of interest included corticosteroid type and dose, local anesthetic type, and total injectate volume for each large joint or bursa (hip, knee, and shoulder).

Results

Most respondents used triamcinolone (50% to 56% of physicians, depending on injection location) or methylprednisolone (25% to 29% of physicians), 21 to 40 mg (53% to 60% of physicians), diluted with lidocaine (79% to 87%) for all large joint or bursa injections. It was noted that 36.2% (244/674) of respondents reported using >40 mg for at least one injection type. Most (90.5%, 610/674) reported using an anesthetic other than ropivacaine for at least one type of joint or bursa injection. Physicians who reported lidocaine use were less likely to report that their injectate choice was based on the literature that they reviewed (odds ratio [OR] 0.41 [0.27‐0.62], P < .001). Respondents predominantly used 5 to 7 mL of total injectate for all large joints or bursae (45% to 54% of respondents), except for the pes anserine bursa, where 3‐4 mL was more common (51% of physicians).

Conclusions

It appears that triamcinolone and methylprednisolone are the most commonly used corticosteroids for sports medicine physicians; most physicians use 21 to 40 mg of corticosteroid for all injections, and lidocaine is the most‐often used local anesthetic; very few use ropivacaine. Over one‐third of respondents used high‐dose (>40 mg triamcinolone or methylprednisolone) for at least one joint or bursa.
Formation of luminescent states in polybenzimidazole‐based films
Authors: Akovantseva Anastasiya , Kotova Svetlana , Gromov Oleg , Burdukovskii Vitaliy , Kholkhoev Bato , Timashev Peter , Yusupov Vladimir , Rybaltovsky Аleksey
Published: September 2020

Here we present the results of experimental studies and theoretical computations of the spectroscopic parameters of polybenzimidazole (PBI) films formed by casting from a formic acid solution. The kinetics of the polymer luminescence is described, depending on the amount of the residual solvent. We demonstrate the changes in the intensity of the film luminescence with the formic acid release from the film, which is confirmed by the IR data. Based on the quantum chemistry computations, a mechanism is suggested for the formation of absorption and luminescence bands characteristic of the PBI matrix.
Modular, synthetic, thiol‐ene mediated hydrogel networks as potential scaffolds for 3D cell cultures and tissue regeneration
Authors: Lüchow Mads , Fortuin Lisa , Malkoch Michael
Published: September 2020

Natural polymers such as collagen are popular materials for tissue engineering scaffolds due to their innate bioactivity and biocompatibility. Being derived from animal sources, however, means that batch‐to‐batch consistency is often low and the extraction of collagen is costly. This conundrum facilitates the need for synthetic alternatives as scaffolding materials. In this study, a system of poly(ethylene glycol) (PEG)‐based thiol‐ene coupled (TEC) hydrogel scaffolds is presented for tissue engineering purposes. The platform includes several necessary features, namely cytocompatibility, high swelling ability, biodegradability, tunable stiffness, and fast, straightforward fabrication. The swelling ability is provided by the hydrophilicity of the ether‐links of PEG, which facilitated the formation of high water content hydrogels that match the water content of soft tissues for the proper diffusion of nutrients and waste compounds. TEC ensures fast and facile fabrication, with cross‐linking moieties that allow for the biodegradation of the hydrogel network through hydrolytic cleavage. The mechanical properties of the scaffolds are made tunable in the range of storage moduli spanning <1 kPa to >100 kPa. It is also shown that despite the synthetic nature of the hydrogels, human dermal fibroblasts and murine macrophages, Raw 264.7, were able to survive and produce extracellular protein excretions while embedded in the 3D hydrogels.
Cystic fibrosis year in review 2019: Section 2 pulmonary disease and infections
Authors: Savant Adrienne P. , McColley Susanna A.
Published: September 2020

During the year 2019, research and case reports or series in the field of cystic fibrosis (CF) were in abundance. To adequately address the large body of CF research published during 2019, the CF year in review will be divided into three sections. This report is the second section, focusing specifically on new research related to pulmonary disease and infections. Additional sections will concentrate on CF transmembrane conductance regulator modulators and the multisystem effects of CF. It is an exciting time to be providing care for patients and their families with CF with all the exciting new discoveries that will be shared in these reviews.