bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasound Shear Wave Elastography to Assess Tissue Mechanical Properties in Somatic Dysfunction: A Feasibility Study
Authors: Gao Jing , Caldwell Judy , Wells Michael , Park David
Published: August 2020

Context

Diagnosis of somatic dysfunction is based on subjective palpatory osteopathic assessments. This subjectivity has posed a challenge for researchers in studying osteopathic medicine. The development and use of radiological imaging techniques to objectively confirm or quantify muscle tissue stiffness associated with somatic dysfunction could be of benefit in osteopathic clinical practice, training, and further research.

Objectives

To investigate the feasibility of ultrasound shear wave elastography (SWE) to quantify muscle tissue stiffness in somatic dysfunction before and after osteopathic manipulative treatment (OMT).

Methods

In this prospective study, we assessed lumbar spine somatic dysfunction in 20 adult patients before and after a single OMT session using standard osteopathic palpatory assessments by osteopathic physician faculty members in the Department of Osteopathic Principle and Practice at Rocky Vista University College of Osteopathic Medicine (Utah campus). Shear wave velocity (SWV, m/s) was measured in lumbar paraspinal muscle tissue using a commercial ultrasonography scanner on all participants immediately before and after OMT. In this study, OMT techniques targeted the iliocostalis lumborum and included the articulatory technique, balanced ligamentous tension, facilitated positional release, high-velocity, low-amplitude technique, muscle energy, myofascial release, and the Still technique at the discretion of the osteopathic physician. The difference in SWV between muscle tissues with and without dysfunction, and differences in SWV of dysfunctional tissue before and after OMT were examined using unpaired and paired t tests, as appropriate. The correlation between SWV measurements and osteopathic assessments was examined by the Spearman rank correlation. Intra- and interobserver reliability was analyzed using intraclass correlation coefficient.

Results

The difference in SWV between muscle tissues with and without somatic dysfunction was significant before OMT (mean [SD], 1.93 [0.44] vs 1.69 [0.19]; P=.03) and was not significant after OMT (mean [SD], 1.69 [0.19] vs 1.53 [0.31]; P=.05). The difference in SWV in the same tissue with somatic dysfunction before and after OMT was significant (mean [SD], 1.93 [0.44] vs 1.52 [0.3]; P<.001). The SWV value highly correlated with manual osteopathic assessments (r=0.72). Intra- and interobserver reliability for performing SWE in somatic dysfunction was good (intraclass correlation coefficient >0.80).

Conclusions

The results of this study show that ultrasound SWE can objectively assess muscle tissue stiffness for diagnosis of somatic dysfunctions and for muscle tissue stiffness changes after OMT.
Geographic population genetic structure and diversity of Sophora moorcroftiana based on genotyping-by-sequencing (GBS)
Authors: Liu Ying , Yi Fei , Yang Guijuan , Wang Yuting , Pubu Ciren , He Runhua , Xiao Yao , Wang Junchen , Lu Nan , Wang Junhui , Ma Wenjun
Published: August 2020

Sophora moorcroftiana is a perennial leguminous low shrub endemic to the Yarlung Zangbo River basin in Tibet with irreplaceable economic and ecological value. To determine the drivers of evolution in this species, 225 individuals belonging to 15 populations from different geographic locations were sampled, and population genetics was studied using high-throughput genotyping-by-sequencing (GBS). Based on genetic diversity analysis, phylogenetic analysis, principal component analysis, and structure analysis, 15 natural populations were clustered into the following five subgroups: subgroup I (Shigatse subgroup) was located in the upper reaches of the Yarlung Zangbo River with a relatively high level of population genetic variation (means for PIC, Shannon and PI were 0.173, 0.326 and 0.0000305, respectively), and gene flow within the subgroup was also high (mean value for Nm was 4.67). Subgroup II (including Pop 7 and Pop 8; means for PIC, Shannon and PI were 0.182, 0.345 and 0.0000321, respectively), located in the middle reaches of the Yarlung Zangbo River had relatively high levels of gene flow with the populations distributed in the upper and lower reaches. The Nm between subgroup II with subgroups I and III was 3.271 and 2.894, respectively. Considering all the genetic diversity indices Pop 8 had relatively high genetic diversity. Subgroup III (the remaining mixed subgroup of Lhasa and Shannan) was located in the middle reaches of the Yarlung Zangbo River and the means for PIC, Shannon and PI were 0.172, 0.324 and 0.0000303, respectively. Subgroup IV (Nyingchi subgroup), located in the lower reaches of the Yarlung Zangbo River basin, showed a further genetic distance from the other subgroups and the means for PIC, Shannon and PI were 0.147, 0.277 and 0.0000263, respectively. Subgroup V (Nyingchi Gongbu Jiangda subgroup), located in the upper reaches of the Niyang River, had the lowest level of genetic variation (means for PIC, Shannon and PI were 0.106, 0.198 and 0.0000187, respectively) and gene flow with other populations (mean value for Nm was 0.42). According to the comprehensive analysis, the S. moorcroftiana populations generally expanded from upstream to downstream and displayed a high level of genetic differentiation in the populations in the upper and lower reaches. There were high levels of gene exchange between the central populations with upstream and downstream populations, and wind-induced seed dispersal was an important factor in the formation of this gene exchange mode.
Downregulation of STK4 promotes colon cancer invasion/migration through blocking β‐catenin degradation
Authors: Lin Cheng‐Han , Hsu Tai‐I , Chiou Pei‐Yu , Hsiao Michael , Wang Wen‐Ching , Chen Yu‐Chia , Lin Jen‐Tai , Wang Jaw‐Yuan , Lin Peng‐Chan , Lin Forn‐Chia , Tseng Yu‐Kai , Cheng Hui‐Chuan , Chen Chi‐Long , Lu Pei‐Jung
Published: August 2020

Mammalian STE20‐like kinase 1 (MST1/STK4/KRS2) encodes a serine/threonine kinase that is the mammalian homolog of Drosophila Hippo. STK4 plays an important role in controlling cell growth, apoptosis, and organ size. STK4 has been studied in many cancers with previous studies indicating an involvement in colon cancer lymph node metastasis and highlighting its potential as a diagnostic marker for colon cancer. However, the role of STK4 defect in promoting colon cancer progression is still understudied. Here, we found that STK4 was significantly downregulated in colon cancer and was associated with distal metastasis and poor survival. Furthermore, STK4 knockdown enhanced sphere formation and metastasis in vitro and promoted tumor development in vivo. We found that STK4 colocalized with β‐catenin and directly phosphorylated β‐catenin resulting in its degradation via the ubiquitin‐mediated pathway. This may suggest that STK4 knockdown causes β‐catenin phosphorylation failure and subsequently β‐catenin accumulation, consequently leading to anchorage‐independent growth and metastasis in colon cancer. Our results support that STK4 may act as a potential candidate for the assessment of β‐catenin‐mediated colon cancer prognosis.
Physical activity, obesity and sedentary behavior in cancer etiology: epidemiologic evidence and biologic mechanisms
Authors: Friedenreich Christine M. , Ryder‐Burbidge Charlotte , McNeil Jessica
Published: August 2020

An estimated 30–40% of cancers can be prevented through changes in modifiable lifestyle and environmental risk factors known to be associated with cancer incidence. Despite this knowledge, there remains limited awareness that these associations exist. The purpose of this review article was to summarize the epidemiologic evidence concerning the contribution of physical activity, sedentary behavior, and obesity to cancer etiology and to provide an overview of the biologic mechanisms that may be operative between these factors and cancer incidence. Strong and consistent evidence exists that higher levels of physical activity reduce the risk of six different cancer sites (bladder, breast, colon, endometrial, esophageal adenocarcinoma, gastric cardia), whereas moderate evidence inversely associates physical activity with lung, ovarian, pancreatic and renal cancer, and limited evidence inversely correlates physical activity with prostate cancer. Sedentary behavior, independent of physical activity, has been shown to increase the risk of colon, endometrial, and lung cancers. Obesity is an established risk factor for 13 different cancer sites (endometrial, postmenopausal breast, colorectal, esophageal, renal/kidneys, meningioma, pancreatic, gastric cardia, liver, multiple myeloma, ovarian, gallbladder, and thyroid). The main biologic mechanisms whereby physical activity, sedentary behavior, and obesity are related to cancer incidence include an effect on endogenous sex steroids and metabolic hormones, insulin sensitivity, and chronic inflammation. Several emerging pathways related to oxidative stress, DNA methylation, telomere length, immune function, and gut microbiome are presented. Key recommendations for future research in both the epidemiology and biology of the associations between physical activity, sedentary behavior, obesity, and cancer risk are also provided.
Microenvironmental modulation of the developing tumour: an immune‐stromal dialogue
Authors: Jones James O. , Moody William M. , Shields Jacqueline D.
Published: August 2020

Successful establishment of a tumour relies on a cascade of interactions between cancer cells and stromal cells within an evolving microenvironment. Both immune and nonimmune cellular components are key factors in this process, and the individual players may change their role from tumour elimination to tumour promotion as the microenvironment develops. While the tumour–stroma crosstalk present in an established tumour is well‐studied, aspects in the early tumour or premalignant microenvironment have received less attention. This is in part due to the challenges in studying this process in the clinic or in mouse models. Here, we review the key anti‐ and pro‐tumour factors in the early microenvironment and discuss how understanding this process may be exploited in the clinic.
Chemokine‐like factor 1 (CKLF1) aggravates neointimal hyperplasia through activating the NF‐κB /VCAM‐1 pathway
Authors: Liu Xinnong , Qu Chengjia , Zhang Yongbao , Fang Jie , Teng Lequn , Zhang Rujiao , Zhang Xiangyu , Shen Chenyang
Published: August 2020

Neointimal hyperplasia (NIH) is a complicated inflammatory process contributing to vascular restenosis. The present study aimed to explore whether chemokine‐like factor 1 (CKLF1) aggravates NIH via the nuclear factor‐kappa B (NF‐κB)/vascular cell adhesion molecule‐1 (VCAM‐1) pathway. We found the expression of CKLF1 and VCAM‐1 significantly increased in human carotid plaques compared to the control. In vivo, CKLF1 overexpression induced a thicker neointimal formation and VCAM‐1 expression was correspondingly upregulated. In vitro, CKLF1 activated NF‐κB and induced VCAM‐1 upregulation in human aortic smooth muscle cells (HASMCs). Functional experiments demonstrated that CKLF1 promoted monocyte adhesion and HASMC migration via VCAM‐1. These results suggest CKLF1 accelerates NIH by promoting monocyte adhesion and HASMC migration via the NF‐κB/VCAM‐1 pathway. Our findings contribute to a better understanding of the mechanisms underlying the causality of CKLF1 on NIH and could prove beneficial in designing therapeutic modalities with a focus on CKLF1.
Determination of machine‐specific tolerances using statistical process control analysis of long‐term uniform scanning proton machine QA results
Authors: Rana Suresh , Eckert Colton , Singh Hardev , Zheng Yuanshui , Chacko Michael , Storey Mark , Chang John
Published: August 2020

Purpose

The purpose of this study was twofold: (a) report the long‐term monthly quality assurance (QA) dosimetry results of the uniform scanning beam delivery system, and (b) derive the machine‐specific tolerances based on the statistic process control (SPC) methodology and compare them against the AAPM TG224 recommended tolerances.

Methods

The Oklahoma Proton Center has four treatment rooms (TR1, TR2, TR3, and TR4) with a cyclotron and a universal nozzle. Monthly QA dosimetry results of four treatment rooms over a period of 6 yr (Feb 2014–Jan 2020) were retrieved from the QA database. The dosimetry parameters included dose output, range, flatness, and symmetry. The monthly QA results were analyzed using the SPC method, which included individuals and moving range (I‐MR) chart. The upper control limit (UCL) and lower control limit (LCL) were set at 3σ above and below the mean value, respectively.

Results

The mean difference in dose output was −0.3% (2σ = ±0.9% and 3σ = ±1.3%) in TR1, 0% (2σ = ±1.4% and 3σ = ±2.1%) in TR2, −0.2% (2σ = ±1.0% and 3σ = ±1.6%) in TR3, and −0.5% (2σ = ±0.9% and 3σ = ±1.3%) in TR4. The mean flatness and symmetry differences of all beams among the four treatment rooms were within ±1.0%. The 3σ for the flatness difference ranged from ±0.5% to ±1.2%. The 3σ for the symmetry difference ranged from ±0.4% to ±1.4%. The SPC analysis showed that the 3σ for range 10 cm (R10), R16, and R22 were within ±1 mm, whereas the 3σ for R28 exceeded ±1 mm in two rooms (3σ = ±1.9 mm in TR2 and 3σ = ±1.3 mm in TR3).

Conclusion

The 3σ of the dose output, flatness, and symmetry differences in all four rooms were comparable to the TG224 tolerance (±2%). For the uniform scanning system, if the measured range is compared against the requested range, it may not always be possible to achieve the range difference within ±1 mm (TG224) for all the ranges.
Source Handler telephone interactions with covert human intelligence sources: An exploration of question types and intelligence yield
Authors: Nunan Jordan , Stanier Ian , Milne Rebecca , Shawyer Andrea , Walsh Dave
Published: August 2020

Law Enforcement Agencies gather intelligence in order to prevent criminal activity and pursue criminals. In the context of human intelligence collection, intelligence elicitation relies heavily upon the deployment of appropriate evidence‐based interviewing techniques (a topic rarely covered in the extant research literature). The present research gained unprecedented access to audio recorded telephone interactions (N = 105) between Source Handlers and Covert Human Intelligence Sources (CHIS) from England and Wales. The research explored the mean use of various question types per interaction and across all questions asked in the sample, as well as comparing the intelligence yield for appropriate and inappropriate questions. Source Handlers were found to utilise vastly more appropriate questions than inappropriate questions, though they rarely used open‐ended questions. Across the total interactions, appropriate questions (by far) were associated with the gathering of much of the total intelligence yield. Implications for practise are discussed.
Association Between Specimen Length and Number of Sections and Diagnostic Yield of Temporal Artery Biopsy for Giant Cell Arteritis
Authors: Muratore Francesco , Boiardi Luigi , Cavazza Alberto , Tiengo Giacomo , Galli Elena , Aldigeri Raffaella , Pipitone Nicolò , Cimino Luca , Bonacini Martina , Croci Stefania , Salvarani Carlo
Published: August 2020

Objective

To investigate the association between specimen length and number of sections evaluated and the diagnostic yield of temporal artery biopsy (TAB) for giant cell arteritis (GCA).

Methods

A pathologist reviewed all TABs performed for suspected GCA between January 1991 and December 2012. The blocks of all the inadequate and negative biopsy specimens were recut, and further slides at deeper levels were stained with hematoxylin and eosin in order to avoid missing inflammatory changes.

Results

In total, findings from 662 TABs were included in the study (71% female; mean age 73.2 years). A total of 427 TAB specimens (65%) were classified as negative, and 235 (35%) were classified as positive for GCA. Compared to those with negative TAB results, patients with positive TAB results were older and more frequently female. There was no difference in postfixation TAB specimen length between TAB specimens negative and positive for GCA (mean 6.5 mm versus 6.9 mm; P = 0.068). Cuts of additional biopsy sections revealed inflammation at deeper levels in 26 of 408 TAB specimens (6.4%) originally reported as uninflamed. The inflamed section was the second in 14 TAB specimens, the third in 9 specimens, and the fourth in 3 specimens. Piecewise logistic regression identified 5 mm as the TAB specimen length change point for diagnostic sensitivity. Compared to a TAB specimen length of <5 mm, the age‐ and sex‐adjusted odds ratio for positive TAB results in samples ≥5 mm long was 1.5 (95% confidence interval 1.0–2.0), P = 0.032.

Conclusion

A postfixation TAB specimen length of at least 5 mm should be sufficient to make a histologic diagnosis of GCA. In order not to miss inflammatory changes, at least 3 further sections at deeper levels should be evaluated in all negative TAB specimens.
Cachexia in Systemic Lupus Erythematosus: Risk Factors and Relation to Disease Activity and Damage
Authors: Stojan George , Li Jessica , Wittmaack Amaya , Petri Michelle
Published: August 2020

Objective

Cachexia is a disorder characterized by involuntary weight loss in addition to loss of homeostatic control of both energy and protein balance. Despite an abundance of data from other inflammatory diseases, cachexia in systemic lupus erythematosus (SLE) remains a largely undescribed syndrome. The present study was undertaken to define the prevalence of cachexia in SLE and to identify the main factors that place patients at risk of developing cachexia.

Methods

A total of 2,452 patients in a prospective SLE cohort had their weight assessed at each visit. Patients were categorized into 5 predetermined groups based on weight. Cachexia was defined based on modified Fearon criteria (5% stable weight loss in 6 months without starvation relative to the average weight in all prior visits and/or a weight loss of >2% without starvation relative to the average weight in all prior cohort visits and a body mass index [BMI] of <20 kg/m2). Risk of cachexia within 5 years of cohort entry was based on Kaplan‐Meier estimates. The association of prior disease manifestations with risk of cachexia adjusted by current steroid use was determined using Cox regression. An analysis of variance test was used to determine whether Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) scores varied based on cachexia status.

Results

Within 5 years of cohort entry, 56% of patients developed cachexia, 18% of which never recovered their weight during follow‐up. The risk factors for cachexia development were a BMI of <20 kg/m2, current steroid use, vasculitis, lupus nephritis, serositis, hematologic lupus manifestations, positive anti–double‐stranded DNA, anti‐Sm, and anti‐RNP. Patients with intermittent cachexia had significantly higher SDI scores compared to those with continuous cachexia or without cachexia.

Conclusion

Cachexia is an underrecognized syndrome in patients with SLE. SLE patients with intermittent cachexia have the highest risk of future organ damage.
Patterns and Correlates of Self‐Management Strategies for Osteoarthritis‐Related Pain Among Older Non‐Hispanic Black and Non‐Hispanic White Adults
Authors: Johnson Alisa J. , Sibille Kimberly T. , Cardoso Josue , Terry Ellen L. , Powell‐Roach Keesha L. , Goodin Burel , Staud Roland , Redden David , Fillingim Roger B. , Booker Staja Q.
Published: August 2020

Objective

Knee osteoarthritis (OA) is a leading source of pain and disability among older adults. Self‐management (SM) strategies are recommended to manage OA symptoms. Sociodemographic and clinical characteristics, along with other factors, may influence SM utilization rate. This study sought to examine the prevalence and correlates of SM use for pain among non‐Hispanic Black patients (NHB) and non‐Hispanic White patients (NHW) older adults with or at risk for knee OA.

Methods

A secondary data analysis was conducted on the Understanding Pain and Limitations in Osteoarthritic Disease multisite observational study, which included NHB (n = 104) and NHW (n = 98) community‐dwelling older adults with or at risk for knee OA. Participants completed measures of sociodemographics, pain SM use, coping, and clinical and experimental pain.

Results

Clinical and experimental pain were significantly greater among NHBs compared to NHWs. There were no significant differences in use of total SM by ethnicity/race. Interestingly, multiple linear regression revealed that clinical and experimental pain indices, as well as coping, number of pain sites, age, and sex were differentially associated with total SM use between NHBs and NHWs. There were significant ethnicity/race by type of pain management interaction effects for pain measures.

Conclusion

SM is common among older adults with or at risk for knee OA pain, and the prevalence of SM does not differ by ethnicity/race, but many guideline‐recommended interventions for OA are underutilized. Importantly, different factors were associated with the use of SM, highlighting distinct biopsychosocial mechanisms contributing to SM use in NHBs and NHWs.
Major Depression and Adverse Patient‐Reported Outcomes in Systemic Lupus Erythematosus: Results From a Prospective Longitudinal Cohort
Authors: Dietz Brett , Katz Patricia , Dall’Era Maria , Murphy Louise B. , Lanata Cristina , Trupin Laura , Criswell Lindsey A. , Yazdany Jinoos
Published: August 2020

Objective

Health‐related quality of life (HRQoL) is reduced in systemic lupus erythematosus (SLE), partly driven by comorbid depression. Among patients with SLE, the association between major depression and HRQoL, measured using the NIH’s Patient‐Reported Outcomes Measurement Information System (PROMIS), is not well characterized. The objective was to determine an association between major depression and HRQoL as measured by PROMIS.

Methods

Cross‐sectional data were obtained from the California Lupus Epidemiology Study, a cohort of adults in the San Francisco Bay Area with SLE. We studied the association between major depression (score ≥10 on the Patient Health Questionnaire 8 depression scale) and T scores (scaled to population mean ± SD of 50 ± 10) on 12 PROMIS domains representing physical, mental, and social health. Mean T scores in depressed and nondepressed individuals were compared using multiple linear regression models adjusting for age, sex, race/ethnicity, disease activity, damage, body mass index, and household income.

Results

Mean age of the 326 participants was 45 years; ~89% were women, 29% White, 23% Hispanic, 10% African American, and 36% Asian. One‐fourth met the criteria for major depression. In multivariable analyses, major depression was independently associated with worse T scores on all 12 PROMIS domains (P < 0.001); compared with those without major depression, depressed individuals scored >10 points (1 SD) worse on fatigue, sleep impairment, negative psychosocial impact of illness, satisfaction in discretionary social activities, and satisfaction in social roles.

Conclusion

In individuals with SLE, major depression is associated with markedly worse PROMIS scores in physical, mental, and social domains. Diagnosing and treating depression may help improve HRQoL in individuals with SLE.
Associations Between Cadence and Knee Loading in Patients With Knee Osteoarthritis
Authors: Hart Harvi F. , Birmingham Trevor B. , Primeau Codie A. , Pinto Ryan , Leitch Kristyn , Giffin J. Robert
Published: August 2020

Objective

To test the hypothesis that higher walking cadence is associated with lower knee loading, while controlling for walking speed, in patients with medial compartment tibiofemoral osteoarthritis (OA).

Methods

A total of 691 patients underwent quantitative gait analysis, including 3‐dimensional knee moments and temporospatial parameters. Using multivariate linear regression, we tested the association of walking cadence with the knee adduction moment angular impulse (a surrogate measure of medial knee compartment load throughout the stance), while controlling for walking speed. We repeated the analysis while also adjusting for sex, age, body mass index, radiographic OA, knee pain, lateral trunk lean, foot progression angle, and mechanical axis angle, and while replacing the knee adduction moment angular impulse with other surrogate measures of knee loading.

Results

While controlling for walking speed, we found that a lower cadence was associated with higher knee adduction moment angular impulse (standardized β = –0.396, P < 0.001), suggesting a 0.02% body weight × height × seconds (%BW × Ht × s) decrease in impulse for each step per minute increase in cadence (unstandardized β –0.020 %BW × Ht × s [95% confidence interval –0.027, –0.015]), and remained consistent after adjusting for covariates. A lower cadence was also associated with higher first (standardized β = –0.138, P = 0.010) and second peak knee adduction moment (standardized β = –0.132, P = 0.018), higher peak knee flexion moment (standardized β = –0.128, P = 0.049), and vertical ground reaction force (standardized β = –0.116, P = 0.035) in the adjusted analyses.

Conclusion

When controlling for walking speed, we found that a lower cadence is associated with higher knee loading per step in patients with medial tibiofemoral OA. Future research should investigate the potential beneficial biomechanical and clinical effects of increasing walking cadence in patients with knee OA.
Efficacy and Safety of Pharmacologic Interventions in Patients Experiencing a Gout Flare: A Systematic Review and Network Meta‐Analysis
Authors: Zeng Linan , Qasim Anila , Neogi Tuhina , Fitzgerald John D. , Dalbeth Nicola , Mikuls Ted R. , Guyatt Gordon H. , Brignardello‐Petersen Romina
Published: August 2020

Objective

To compare the relative efficacy and safety of pharmacologic antiinflammatory interventions for gout flares.

Methods

We searched Ovid Medline, Embase, and Cochrane library for randomized controlled trials (RCTs) that compared pharmacologic antiinflammatory treatment of gout flares. We conducted a network meta‐analysis (NMA) using a frequentist framework and assessed the certainty of evidence and made conclusions using the Grading of Recommendations Assessment, Development, and Evaluation for NMA.

Results

In the 30 eligible RCTs, canakinumab provided the highest pain reduction at day 2 and at longest follow‐up (mean difference relative to acetic acid derivative nonsteroidal antiinflammatory drugs [NSAIDs] –41.12 [95% confidence interval (95% CI) –53.36, –29.11] on a 0–100 scale at day 2, and mean difference –12.84 [95% CI –20.76, –4.91] at longest follow‐up; both moderate certainty; minimum important difference –19). Intravenous or intramuscular corticosteroids were inferior to canakinumab but may be better than the other commonly used interventions (low to very low certainty). For joint tenderness, canakinumab may be the most effective intervention at day 2. Acetic acid derivative NSAIDs improved joint swelling better than ibuprofen NSAIDs at day 2 (mean difference –0.29 [95% CI –0.56, –0.02] on a 0–4 scale; moderate certainty) and improved patient global assessment (PtGA) greater than ibuprofen NSAIDs at the longest follow‐up (mean difference –0.44 [95% CI –0.86, –0.02]; moderate).

Conclusion

Canakinumab may be superior to other alternatives and intravenous or intramuscular corticosteroids may be the second best in pain reduction. Acetic acid derivative NSAIDs may be superior to ibuprofen NSAIDs in improving joint swelling and PtGA.
Mortality Among Patients With Polymyalgia Rheumatica: A Retrospective Cohort Study
Authors: Partington Richard , Muller Sara , Mallen Christian D. , Abdul Sultan Alyshah , Helliwell Toby
Published: August 2020

Objective

To determine whether a diagnosis of polymyalgia rheumatica (PMR) is associated with premature mortality.

Methods

We extracted anonymized electronic medical records of patients ages >40 years who were eligible for linkage with the Office for National Statistics Death Registration data set, from the Clinical Practice Research Datalink from 1990 to 2016. Patients with PMR were individually matched, by age, sex, and registered general practice, with up to 5 controls without PMR. The total number and proportion of deaths and mortality rates were calculated. The mortality rate ratio (MRR) with 95% confidence interval (95% CI), adjusted for age, sex, region, smoking status, body mass index, and alcohol consumption, was calculated using Poisson regression. The 20 most common causes of death were tabulated.

Results

A total of 18,943 patients with PMR were matched to 87,801 controls. The mean ± SD follow‐up after date of diagnosis was 8.0 ± 4.4 years in patients with PMR and 7.9 ± 4.6 years in controls. PMR was not associated with an increase in the risk of death (adjusted MRR 1.00 [95% CI 0.97–1.03]) compared to matched controls. Causes of death were broadly similar between patients with PMR and controls, although patients with PMR were slightly more likely to have a vascular cause of death recorded (24% versus 23%).

Conclusion

A diagnosis of PMR does not appear to increase the risk of premature death. Minor variations in causes of death were observed, but overall this study is reassuring for patients with PMR and for clinicians.
High‐efficiency Practices of Residents in an Academic Emergency Department: A Mixed‐methods Study
Authors: Egan Haley M. , Swanson Morgan B. , Ilko Steven A. , Pomeranz Kaila A. , Mohr Nicholas M. , Ahmed Azeemuddin
Published: August 2020

Background

Emergency department utilization and crowding is increasing, putting additional pressure on emergency medicine (EM) residency programs to train efficient residents who can meet these demands. Specific practices associated with resident efficiency have yet to be identified. The objective of this study was to identify practices associated with enhanced efficiency in EM residents.

Methods

A mixed‐methods study design was utilized to identify behaviors associated with resident efficiency. In Stage 1, eight EM faculty provided 61 efficiency behaviors during semistructured interviews, which were prioritized into eight behaviors by independent ranking. A total of 31 behaviors were tested, including additions from previous literature and the study team. In Stage 2, two 4‐hour observations during separate shifts of 27 EM residents were performed to record minute‐by‐minute timing and frequency of each behavior. In Stage 3, the association between resident efficiency and each of the behaviors was estimated using multivariable regression models adjusted for training year and clustered on resident. The primary efficiency outcome was 6‐month average relative value units/hour. A sensitivity analysis was performed using patients/hour.

Results

Seven practices were positively associated with efficiency: average patient load, taking initial patient history with nurse present (number/hour, number/new patient), running the board (number/hour), conversations with other care team members (number/hour, % time), dictation use (number/hour, % time), smartphone text communication (number/hour, % time), and nonwork tasks (number/hour). Three practices were negatively associated with efficiency: visits to patient room (number/patient), conversations with attending physicians (% time), and reviewing electronic medical record (number/hour).

Conclusion

Several discrete behaviors were found to be associated with enhanced resident efficiency. These results can be utilized by EM residency programs to improve resident education and inform evaluations by providing specific, evidence‐based practices for residents to develop and improve upon throughout training.
Flow, suspension and mixing dynamics in DASGIP bioreactors, Part 2
Authors: Samaras Jasmin J. , Ducci Andrea , Micheletti Martina
Published: August 2020

This work aims to characterize the mixing and suspension dynamics occurring within two commercially available DASGIP bioreactor configurations, equipped with a two‐blade paddle impeller with large impeller to tank diameter ratio, D/T = 0.97. Both continuous and intermittent agitation modes were employed to determine the impact that agitation strategy has upon mass transfer and microcarrier settling/suspension. This paper builds upon the flow dynamics data presented in Part 1 for a flat bottom DASGIP bioreactor and shows how intermittent agitation can break‐up regions of slow mixing observed during continuous agitation, therefore substantially increasing the mixing efficiency of the system. Similarly, it was found that microcarrier characteristics might significantly affect the level of suspension when the impeller is in dwell status when intermittent agitation modes are used.
Iron oxide‐loaded polymer scaffolds for non‐invasive hyperthermic treatment of infiltrated cells
Authors: Lam Tiffany , Moy Alyssa , Lee Hak Rae , Shao Qi , Bischof John C. , Azarin Samira M.
Published: August 2020

Focal therapies such as hyperthermia have been successfully used to treat solid localized tumors; however, they are not easily applied to cancers that may present in a disseminated form such as ovarian cancer. To address this need, iron oxide (IO) particles were incorporated into microporous poly(caprolactone) scaffolds previously shown to recruit disseminating cancer cells. Under an alternating magnetic field, IO‐loaded scaffolds exhibited heating and killed ID8 ovarian cancer cells in vitro. After implantation in the intraperitoneal cavity of mice, IO‐loaded scaffolds became infiltrated with tissue after 6–7 weeks, and infiltrated cells were successfully treated ex vivo. Finally, IO‐loaded scaffolds noninvasively killed infiltrated cells in vivo as evidenced by decreases in number of nuclei. These studies demonstrate the promising use of IO‐loaded scaffolds as a tool for noninvasive hyperthermia, which could be an innovative modality for treatment of disseminated cancers.
Waves in a rivulet falling down an inclined cylinder
Authors: Aktershev Sergey , Alekseenko Sergey , Bobylev Aleksey
Published: August 2020

In the long‐wave approximation, a theoretical model is developed to describe waves in a rivulet flowing down the lower surface of an inclined cylinder. The model equations are derived by the weighted residual method by projecting the Navier–Stokes equations onto the constructed system of basic orthogonal polynomials. The simplest case of quasi‐two‐dimensional waves is studied in detail. The stability of the rivulet flow is analyzed and dispersion dependences for linear waves are obtained. The characteristics of nonlinear steady‐state traveling waves have been obtained by numerical method for the first time, and the spatial development of forced waves has been studied. The results of calculations are in good agreement with the available experimental data for various liquids in a wide range of parameters.
Effectiveness of safety training interventions for supervisors: A systematic review and narrative synthesis
Authors: Sinelnikov Sergey , Bixler Emily A. , Kolosh Alaina
Published: August 2020

A wealth of research demonstrates that work unit supervisors serve a critical function in protecting the safety and health of workers. A systematic review examined the effectiveness of workplace safety training interventions intended for various supervisor populations published from 2000 to 2019. A search of seven electronic databases was supplemented with hand searches from the reference lists of identified publications, relevant scientific journals, and the gray literature. This review included an assessment of the methodological quality using a modified version of the Quality Assessment Tool for Quantitative Studies. A total of 22 peer‐reviewed studies met a set of inclusion criteria and were subsequently assessed for methodological quality. Training interventions were grouped into five topical domains: ergonomics, leadership, supervisor‐worker interaction, injury, and disability management, and general safety education. Consistent evidence was found for the effectiveness of supervisory training interventions across several outcome measures. To our knowledge, this is the first study to synthesize the literature on supervisory training interventions in the area of occupational safety. While the results are encouraging, they must be viewed with caution due to the fact that the methodological rigor of the reviewed studies was low.
Effects of IgLON5 Antibodies on Neuronal Cytoskeleton: A Link between Autoimmunity and Neurodegeneration
Authors: Landa Jon , Gaig Carles , Plagumà Jesús , Saiz Albert , Antonell Ana , Sanchez‐Valle Raquel , Dalmau Josep , Graus Francesc , Sabater Lidia
Published: August 2020

Anti‐IgLON5 disease is a neurological disorder characterized by autoantibodies against IgLON5 and pathological evidence of neuronal‐specific tau accumulation. Here, we report that patients' IgLON5 IgG, but not other cell‐surface antibodies, disrupt the cytoskeletal organization in cultured rat hippocampal neurons, resulting in dystrophic neurites and axonal swelling. Adsorption of IgLON5 IgG with HEK293 cells expressing IgLON5 abrogated the indicated cytoskeletal changes. These findings, along with an increase of levels of neurofilaments in patients' cerebrospinal fluid, suggest that IgLON5 IgG, unlike other cell‐surface antibodies, disrupts neuronal cytoskeleton maintenance, providing a link between autoimmunity and neurodegeneration. ANN NEUROL 2020;88:1023–1027
Alertness Training Improves Spatial Bias and Functional Ability in Spatial Neglect
Authors: Van Vleet Thomas , Bonato Paolo , Fabara Eric , Dabit Sawsan , Kim Sarah‐Jane , Chiu Christopher , Bisogno Antonio Luigi , Merzenich Michael , Corbetta Maurizio , DeGutis Joseph
Published: August 2020

Objective

We conducted a multisite, randomized, double‐blinded, controlled trial to examine the effectiveness of a digital health intervention targeting the intrinsic regulation of goal‐directed alertness in patients with chronic hemispatial neglect.

Methods

Forty‐nine participants with hemispatial neglect, who demonstrated significant spatially biased attention after acquired brain injury, were randomly assigned to the experimental attention remediation treatment or the active control group. The participants engaged with the remotely administered interventions for 12 weeks. The primary outcome was spatial bias on the Posner cueing task (response time difference: left minus right target trials). Secondary outcomes included functional abilities (measured via the Catherine Bergego scale and Barthel index), spatial cognition, executive function, quality of life, and sleep. Assessments were conducted before and immediately after participation in the experimental intervention or control condition, and again after a 3‐month no‐contact period.

Results

Compared with the active control group, the intervention group exhibited a significant improvement in the primary outcome, a reduction in spatially biased attention on the Posner cueing task (p = 0.010, Cohen's d = 0.96), in addition to significant improvements in functional abilities as measured on the Catherine Bergego and Barthel indices (p = 0.027, Cohen's d = 0.24).

Interpretation

Our results demonstrate that our attention training program was effective in improving the debilitating attention deficits common to hemispatial neglect. This benefit generalized to improvements in real‐world functional abilities. This safe, highly scalable, and self‐administered treatment for hemispatial neglect might serve as a useful addition to the existing standard of care. ANN NEUROL 2020;88:747–758
Antirheumatic Disease Therapies for the Treatment of COVID‐19: A Systematic Review and Meta‐Analysis
Authors: Putman Michael , Chock Yu Pei Eugenia , Tam Herman , Kim Alfred H. J. , Sattui Sebastian E. , Berenbaum Francis , Danila Maria I. , Korsten Peter , Sanchez-Alvarez Catalina , Sparks Jeffrey A. , Coates Laura C. , Palmerlee Candace , Peirce Andrea , Jayatilleke Arundathi , Johnson Sindhu R. , Kilian Adam , Liew Jean , Prokop Larry J. , Murad M. Hassan , Grainger Rebecca , Wallace Zachary S. , Duarte-García Alí ,   the COVID‐19 Global Rheumatology Alliance
Published: August 2020

Objective

Antirheumatic disease therapies have been used to treat coronavirus disease 2019 (COVID‐19) and its complications. We conducted a systematic review and meta‐analysis to describe the current evidence.

Methods

A search of published and preprint databases in all languages was performed. Included studies described ≥1 relevant clinical outcome for ≥5 patients who were infected with severe acute respiratory syndrome coronavirus 2 and were treated with antirheumatic disease therapy between January 1, 2019 and May 29, 2020. Pairs of reviewers screened articles, extracted data, and assessed risk of bias. A meta‐analysis of effect sizes using random‐effects models was performed when possible.

Results

The search identified 3,935 articles, of which 45 were included (4 randomized controlled trials, 29 cohort studies, and 12 case series). All studies evaluated hospitalized patients, and 29 of the 45 studies had been published in a peer‐reviewed journal. In a meta‐analysis of 3 cohort studies with a low risk of bias, hydroxychloroquine use was not significantly associated with mortality (pooled hazard ratio [HR] 1.41 [95% confidence interval (95% CI) 0.83, 2.42]). In a meta‐analysis of 2 cohort studies with some concerns/higher risk of bias, anakinra use was associated with lower mortality (pooled HR 0.25 [95% CI 0.12, 0.52]). Evidence was inconclusive with regard to other antirheumatic disease therapies, and the majority of other studies had a high risk of bias.

Conclusion

In this systematic review and meta‐analysis, hydroxychloroquine use was not associated with benefit or harm regarding COVID‐19 mortality. The evidence supporting the effect of other antirheumatic disease therapies in COVID‐19 is currently inconclusive.
Computer‐based evaluation to assess students' learning for the multiple‐choice question–based exams: CBE‐MCQs software tool
Authors: Solak Serdar , Ucar Mustafa H. B. , Albadwieh Mohammad
Published: August 2020

In this study, a computer‐based evaluation (CBE) software tool, namely CBE‐MCQs, is proposed to assist the instructor to evaluate and analyze traditional classroom‐based exams, which include multiple‐choice questions (MCQs) reliably, quickly, and automatically. Using the proposed CBE‐MCQs software tool while performing question analysis, the learning outcome‐based analyzes are performed by matching the learning outcomes of the courses with the exam questions. With question‐based evaluations, item analyzes such as item difficulty, item discrimination, and item distracters can be made easily. Also, with the question‐based evaluation, the instructor of the course can effectively measure the extent to which students achieve the learning outcomes of the related course. Thus, the CBE‐MCQs tool helps successful maintenance of both accreditation and training processes with the analysis it provides to the instructors. In addition, the final exam assessment of the course based on MCQs within the scope of the case study was carried out with the CBE‐MCQs software tool. Each MCQ was evaluated based on classical theory within the scope of difficulty index (P), discrimination index (D), and distracter efficiency (DE). It is observed that association between D and P was statistically significant according to Pearson correlation (r = −0.600) and χ2 (χ2 = 15.98, df = 8; α = 0.05). Also, a system usability survey of 10 statements was applied to the instructors using this software to evaluate the usability of the CBE‐MCQs software tool. As a result of a series of experimental studies and survey, the developed CBE‐MCQs software tool is evaluated as simple, effective, and satisfactory by 87.4% of the instructors.
Integration of anthracnose resistance loci and RLK and NBS‐LRR‐encoding genes in the Phaseolus vulgaris L. genome
Authors: Vaz Bisneta Mariana , Gonçalves‐Vidigal Maria Celeste
Published: August 2020

The most effective strategy to manage bean anthracnose (ANT), caused by Colletotrichum lindemuthianum, is the use of resistant cultivars. There are more than 20 ANT resistance genes that have been identified and mapped in common bean (Phaseolus vulgaris L.) chromosomes. Moreover, quantitative resistance loci (QRLs) have been described through genome‐wide association studies (GWAS). Identification of pathogen‐responsive genes and proteins on a molecular level provides a better understanding of metabolic pathways involved in ANT resistance. In this study, we investigated typical resistance proteins located close to ANT resistance loci in the common bean reference genome. Among them, we checked for proteins with nucleotide‐binding and leucine‐rich repeat (NBS‐LRR) domains and kinase domains since most resistance genes encode proteins with these domains. In addition, proteins with kinase domains are known to operate as pattern‐recognition receptors that recognize pathogen‐associated molecular patterns (PAMPs) and activate an immune response. Based on the common bean reference genome (Version 2.1), the regions 500‐kb upstream and downstream of the physical position of each ANT resistance locus were considered for a candidate gene search. Thus, an integrated map of ANT resistance loci and candidate genes (encoding defense response‐related proteins) was constructed. This map contains candidate genes for all ANT resistance genes and QRLs previously described in the literature. A total of 256 NBS‐LRR proteins and 200 protein kinases were detected. The functions of the identified candidate genes in ANT response should be validated and studies should be performed to understand how they interact with metabolic pathways.
The stability and variability of maize kernel moisture content at physiological maturity
Authors: Li Lulu , Ming Bo , Xie Ruizhi , Wang Keru , Hou Peng , Gao Shang , Chu Zhendong , Zhang Wanxu , Huang Zhaofu , Li Hongyan , Zhou Xianlin , Li Shaokun
Published: August 2020

Maize (Zea mays L.) kernel moisture content at physiological maturity significantly differs among hybrids and is affected by the environment. Nonetheless, 35% was previously reported and is widely accepted as the moisture content at physiological maturity. To verify whether the 35% moisture content could be applied to various hybrids and regions, a multi‐area, multi‐year trial was conducted from 2015 to 2018 in six locations in different maize‐planting regions of China. Time‐series kernel moisture contents and kernel dry weights were investigated for 156 hybrids in total to ascertain the growth pattern of the percentage maximum kernel dry weight as a function of kernel moisture content. The growth patterns were fitted with a tri‐linear model with a plateau, and at the point at which the percentage maximum kernel dry weight first reached its maximum (physiological maturity), the kernel moisture contents were 32% for summer maize, 34% for spring maize, and 38% for Daqing (a special spring maize region). We found that regional variation existed in kernel moisture content at physiological maturity. The regional average moisture content at physiological maturity could thus be used as an indicator to determine physiological maturity for most hybrids in the region. In addition, varietal differences in moisture content could be accounted for when using the regional average value.