bluuebunny/crossref_metadata_2025 huggingface dataset:
Reaction Force Generation and Mechanical Demand Imposed on the Shoulder When Initiating Manual Wheelchair Propulsion and at Self-Selected Fast Speeds
Authors: Papp Marisa , Russell Ian , Requejo Philip S. , Furumasu Jan , McNitt-Gray Jill L.
Published: November 2019

Manual wheelchair (WC) users with spinal cord injury (SCI) experience shoulder pain and fatigue associated with their increased reliance on the upper extremity during activities of daily living (Bayley et al. 1987, “The Weight-Bearing Shoulder. The Impingement Syndrome in Paraplegics,” J. Bone Jt. Surg. Am., 69(5), pp. 676–678). We hypothesized that the mechanical demand imposed on the shoulder, represented as resultant shoulder net joint moment (NJM) impulse, would be greater when initiating manual WC propulsion from a stationary position without momentum than when manually propelling at speed on a level sidewalk. Thirty manual WC users with paraplegia participated. Each individual initiated manual WC propulsion from a stationary position and propelled on a level sidewalk at their self-selected fast speed. Upper extremity kinematics and pushrim reaction forces (RFs) were measured and upper extremity joint kinetics were calculated and compared (α = 0.05) between cycle 1, initiated without momentum, and cycle 3 with momentum. Results indicate that multiple factors contributing to the mechanical demand imposed on the shoulder were significantly greater when manual WC propulsion was initiated without momentum than with momentum. Significant differences in resultant shoulder NJM impulse, push duration, orientation of RF relative to forearm, and resultant average shoulder NJMs during push were observed between momentum conditions. No significant differences in average resultant RF during push were found. These results indicate that mechanical loading of the shoulder during manual WC propulsion differs between momentum conditions; these differences in resultant shoulder NJM impulse during push need to be considered when assessing shoulder load exposure in stop-and-start activities.
Structural Insight into African Swine Fever Virus dUTPase Reveals a Novel Folding Pattern in the dUTPase Family
Authors: Li Guobang , Wang Changwen , Yang Mengyuan , Cao Lin , Fu Dan , Liu Xiaoxia , Sun Dongdong , Chen Cheng , Wang Ying , Jia Zihan , Yang Cheng , Guo Yu , Rao Zihe
Published: November 2019

African swine fever virus (AFSV), a large enveloped double-stranded DNA virus, causes a deadly infection in domestic pigs. In addition to Africa, Europe, and South America, countries in Asia, such as China, Vietnam, and Mongolia, have suffered the hazards posed by ASFV outbreaks in recent years. Until now, there has been no vaccine for protection from ASFV infection or effective treatments to cure ASF. Here, we solved the crystal structure of the ASFV dUTPase-dUMP-Mg
2+
complex. The ASFV dUTPase displays a noncanonical folding pattern that differs from that of the classic homotrimeric dUTPase, in which the active site is composed of two subunits. In addition, several nonconserved residues within the 3-fold axis channel play a vital role in ASFV dUTPase homotrimer stability. Our finding on these unique structural features of the ASFV dUTPase could be explored for the design of potential specific inhibitors that target this unique enzyme.
Psychological impact of working in paediatric intensive care. A UK-wide prevalence study
Authors: Jones Gareth A L , Colville Gillian A , Ramnarayan Padmanabhan , Woolfall Kerry , Heward Yvonne , Morrison Rachael , Savage Amy , Fraser James , Griksaitis Michael J , Inwald David P
Published: November 2019

Objective

To determine the prevalence of work-related psychological distress in staff working in UK paediatric intensive care units (PICU).

Design

Online (Qualtrics) staff questionnaire, conducted April to May 2018.

Setting

Staff working in 29 PICUs and 10 PICU transport services were invited to participate.

Participants

1656 staff completed the survey: 1194 nurses, 270 physicians and 192 others. 234 (14%) respondents were male. Median age was 35 (IQR 28–44).

Main outcome measures

The Moral Distress Scale-Revised (MDS-R) was used to look at moral distress, the abbreviated Maslach Burnout Inventory to examine the depersonalisation and emotional exhaustion domains of burnout, and the Trauma Screening Questionnaire (TSQ) to assess risk of post-traumatic stress disorder (PTSD).

Results

435/1194 (36%) nurses, 48/270 (18%) physicians and 19/192 (10%) other staff scored above the study threshold for moral distress (≥90 on MDS-R) (χ2 test, p<0.00001). 594/1194 (50%) nurses, 99/270 (37%) physicians and 86/192 (45%) other staff had high burnout scores (χ2 test, p=0.0004). 366/1194 (31%) nurses, 42/270 (16%) physicians and 21/192 (11%) other staff scored at risk for PTSD (χ2 test, p<0.00001). Junior nurses were at highest risk of moral distress and PTSD, and junior doctors of burnout. Larger unit size was associated with higher MDS-R, burnout and TSQ scores.

Conclusions

These results suggest that UK PICU staff are experiencing work-related distress. Further studies are needed to understand causation and to develop strategies for prevention and treatment.
Intent to have a second child among Chinese women of childbearing age following China’s new universal two-child policy: a cross-sectional study
Authors: Liu Jue , Liu Min , Zhang Shikun , Ma Qiuyue , Wang Qiaomei
Published: November 2019

Introduction

China’s one-child policy was replaced by a new universal two-child policy in 2015; however, few studies have addressed the intent to have a second child and resulting related issues.

Methods

We performed a cross-sectional study on 11 991 Chinese women, 18–49 years of age, from 11 provinces in 2016–2017, in order to assess the intent for a second child among Chinese women of childbearing age and other related factors after the introduction of China’s new universal two-child policy.

Results

We found that the overall prevalence of the intent to have a second child was 39.4% and that economic, childrearing, and health barriers affected fertility intent. Multivariate logistic regression models showed that the age range of 25–39 years (aOR 1.28–1.30), living in Eastern (aOR 1.28, 95% CI 1.10 to 1.50) or Central China (aOR 1.52, 95% CI 1.27 to 1.78), living in a rural area (aOR 1.62, 95% CI 1.47 to 1.78), being a farmer (aOR 1.43, 95% CI 1.09 to 1.88), having a higher household income (aOR 1.13, 95% CI 1.00 to 1.28), having a history of abortion (aOR 1.18, 95% CI 1.05 to 1.31), and already having one child (aOR 3.65 for girls, aOR 2.70 for boys) were associated with a greater intent to have a second child (all p<0.05). Conversely, economic, health, childrearing, and educational barriers were associated with a lower intent to have a second child (aOR 0.65–0.75).

Conclusion

Four in ten women of childbearing age demonstrated an intent for a second child. We maintain that fertility-related factors be given full consideration when promoting the two-child policy.
Controlled field study evaluating the clinical efficacy of a topical formulation containing emodepside and praziquantel in the treatment of natural cat aelurostrongylosis
Authors: Crisi Paolo Emidio , Di Cesare Angela , Traversa Donato , Vignoli Massimo , Morelli Simone , Di Tommaso Morena , De Santis Francesca , Pampurini Fabrizio , Schaper Roland , Boari Andrea
Published: November 2019

Background

Aelurostrongylus abstrusus is the most important nematode affecting the respiratory tract of cats in terms of prevalence and clinical relevance. The aim of this randomised controlled field study was to confirm the efficacy of the spot‐on containing emodepside/praziquantel (Profender, Bayer Animal Health) in the treatment of aelurostrongylosis.

Methods

Seventeen cats with aelurostrongylosis and presenting with clinical and/or radiographic signs were included in the study. Eight cats received two biweekly doses of emodepside/praziquantel, while nine cats were allocated to a control group and received a rescue treatment at the end of the study. Clinical response was the primary outcome, while the secondary end point was the reduction of larval shedding in faeces.

Results

Two weeks after the first application, the cats showed a significant, though partial, recovery of clinical signs with complete clinical and parasitological resolution. The resolution of inflammatory leucogram and a significant reduction of radiographic lesions were observed two weeks after the second treatment. Red blood cells and albumin values significantly increased after eight weeks from the second application, together with the complete regression of radiographic patterns.

Conclusion

Two applications of this spot‐on solution two weeks apart assured complete cessation of larval shedding and led to a complete clinical, clinicopathological and radiographic recovery.
Comparing seepage and selenium desorption in blasted-rock fills using two reclamation techniques
Authors: DePriest Nathan , Hopkinson Leslie , Quaranta John
Published: November 2019

Geomorphic reclaimed landforms aim to improve groundwater movement and diminish contaminant transport through increased runoff and reduced groundwater infiltration. The objective of this research was to determine if geomorphic reclamation techniques result in improved selenium concentrations of discharge water as compared to conventional reclamation for valley-fills constructed of blasted rock. Comparisons investigated if groundwater and contaminant desorption could be improved by altering valley-fill construction. Three-dimensional finite-element groundwater modelling was performed on two valley-fill geometries and was coupled with laboratory testing of selenium leaching from blasted-rock overburden. Selenium desorption characteristics and distributions were compared. Lower water volumes and shorter contact times with overburden fill resulted in lower masses of selenium desorbed from geomorphic fills as compared to conventional techniques. When results were normalized by varying fill areas and volumes, the geomorphic valley-fill exhibited 23% lower surface infiltration, 27% lower discharge volumes and 39% lower selenium discharge loads as compared to the conventional reclamation. To achieve these advantages in geomorphic reclamation, infiltration must be reduced through both the construction of curvilinear slopes of the fill surface and the creation of a low infiltration-capacity reclaimed stream.
Short-term muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates
Authors: Kilroe Sean P. , Fulford Jonathan , Holwerda Andrew M. , Jackman Sarah R. , Lee Benjamin P. , Gijsen Annemie P. , van Loon Luc J. C. , Wall Benjamin T.
Published: November 2019

Short-term muscle disuse has been reported to lower both postabsorptive and postprandial myofibrillar protein synthesis rates. This study assessed the impact of disuse on daily myofibrillar protein synthesis rates following short-term (2 and 7 days) muscle disuse under free living conditions. Thirteen healthy young men (age: 20 ± 1 yr; BMI: 23 ± 1 kg/m−2) underwent 7 days of unilateral leg immobilization via a knee brace, with the nonimmobilized leg acting as a control. Four days before immobilization participants ingested 400 mL of 70% deuterated water, with 50-mL doses consumed daily thereafter. Upper leg bilateral MRI scans and muscle biopsies were collected before and after 2 and 7 days of immobilization to determine quadriceps volume and daily myofibrillar protein synthesis rates. Immobilization reduced quadriceps volume in the immobilized leg by 1.7 ± 0.3 and 6.7 ± 0.6% after 2 and 7 days, respectively, with no changes in the control leg. Over the 1-wk immobilization period, myofibrillar protein synthesis rates were 36 ± 4% lower in the immobilized (0.81 ± 0.04%/day) compared with the control (1.26 ± 0.04%/day) leg ( P < 0.001). Myofibrillar protein synthesis rates in the control leg did not change over time ( P = 0.775), but in the immobilized leg they were numerically lower during the 0- to 2-day period (16 ± 6%, 1.11 ± 0.09%/day, P = 0.153) and were significantly lower during the 2- to 7-day period (44 ± 5%, 0.70 ± 0.06%/day, P < 0.001) when compared with the control leg. We conclude that 1 wk of muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates in healthy young men.
Eliminating high-intensity activity during growth reduces mechanical power capacity but not submaximal metabolic cost in a bipedal animal model
Authors: Cox Suzanne Michelle , Salzano Matthew Q. , Piazza Stephen J. , Rubenson Jonas
Published: November 2019

Decreases in activity levels in children worldwide are feared to have long-term health repercussions. Yet, because of the difficulty of performing controlled long-term studies in humans, we do not yet understand how decreases in childhood activity influence adult functional capacity. Here, in an avian bipedal model, we evaluated the elimination of all high-intensity activity during growth on adult performance. We evaluated three alternative hypotheses: Elimination of high-intensity activity 1) does not influence adult function, 2) results in task-specific deficits in adulthood, or 3) results in deficits that generalize across locomotor tasks. We found that animals restricted from jumping and sprinting during growth showed detriments as adults in maximal jump performance in comparison to controls, but did not require more metabolic energy during steady-state running or standing. From this, we conclude that functional deficits from elimination of high-intensity exercise are task specific and do not generalize across all locomotor functions.

NEW & NOTEWORTHY Decreasing childhood activity levels are feared to have long-term health repercussions, but testing this hypothesis is hampered by restrictions of human experimentation. Here, in a bipedal animal model, we examine how the elimination of high-intensity activity during all of maturation influences adult locomotor capacity. We found restricted activity during growth reduced mechanical power capacity but not submaximal metabolic cost. This suggests that reduced childhood activity may result in task-specific, rather than generalized locomotor deficits.
A Data Transmission Strategy with Energy Minimization Based on Optimal Stopping Theory in Mobile Cloud Computing
Authors: Zheng Xin , Nan Yu , Wang Fangsu , Song Ruiqing , Zheng Gang , Wang Gaocai , Lu Yuting , Zhao Qifei
Published: November 2019

Considering the widespread use of mobile devices and the increased performance requirements of mobile users, shifting the complex computing and storage requirements of mobile terminals to the cloud is an effective way to solve the limitation of mobile terminals, which has led to the rapid development of mobile cloud computing. How to reduce and balance the energy consumption of mobile terminals and clouds in data transmission, as well as improve energy efficiency and user experience, is one of the problems that green cloud computing needs to solve. This paper focuses on energy optimization in the data transmission process of mobile cloud computing. Considering that the data generation rate is variable, because of the instability of the wireless connection, combined with the transmission delay requirement, a strategy based on the optimal stopping theory to minimize the average transmission energy of the unit data is proposed. By constructing a data transmission queue model with multiple applications, an admission rule that is superior to the top candidates is proposed by using secretary problem of selecting candidates with the lowest average absolute ranking. Then, it is proved that the rule has the best candidate. Finally, experimental results show that the proposed optimization strategy has lower average energy per unit of data, higher energy efficiency, and better average scheduling period.
Differentiating the Personalized Information of the Physician‐Patient Communication for the Chronic Obstructive Pulmonary Disease with General Probabilistic Vector Linguistic Terms
Authors: Zhai Yuling , Xu Zeshui , Ren Peijia
Published: November 2019

To accurately determine the follow‐up therapeutic schedules for the chronic obstructive pulmonary disease (COPD) patients, this paper aims to develop the analysis tools for the linguistic evaluation to improve the quality of the physician‐patient communication. Firstly, we define the general probabilistic vector linguistic term (GPVLT), which is effective to depict people’s judgements from different sources. Then, we establish the multigranularity linguistic space and discuss the different forms of the probabilistic vector linguistic units (PVLUs) in it. Later on, we propose the nondirectional and the directional potentials of PVLUs, which can grasp the fuzziness and the development direction of the linguistic evaluations, respectively. Last but not least, the cases about the physician‐patient communication for COPD and some comparisons with the other related methods are provided to illustrate the effectiveness and practicability of the PVLUs’ potentials.
Hedgehog Signaling Inhibition by Smoothened Antagonist BMS-833923 Reduces Osteoblast Differentiation and Ectopic Bone Formation of Human Skeletal (Mesenchymal) Stem Cells
Authors: AlMuraikhi Nihal , Almasoud Nuha , Binhamdan Sarah , Younis Ghaydaa , Ali Dalia , Manikandan Muthurangan , Vishnubalaji Radhakrishnan , Atteya Muhammad , Siyal Abdulaziz , Alfayez Musaad , Aldahmash Abdullah , Kassem Moustapha , Alajez Nehad M.
Published: November 2019

Background. Hedgehog (Hh) signaling is essential for osteoblast differentiation of mesenchymal progenitors during endochondral bone formation. However, the critical role of Hh signaling during adult bone remodeling remains to be elucidated. Methods. A Smoothened (SMO) antagonist/Hedgehog inhibitor, BMS-833923, identified during a functional screening of a stem cell signaling small molecule library, was investigated for its effects on the osteoblast differentiation of human skeletal (mesenchymal) stem cells (hMSC). Alkaline phosphatase (ALP) activity and Alizarin red staining were employed as markers for osteoblast differentiation and in vitro mineralization capacity, respectively. Global gene expression profiling was performed using the Agilent® microarray platform. Effects on in vivo ectopic bone formation were assessed by implanting hMSC mixed with hydroxyapatite-tricalcium phosphate granules subcutaneously in 8-week-old female nude mice, and the amount of bone formed was assessed using quantitative histology. Results. BMS-833923, a SMO antagonist/Hedgehog inhibitor, exhibited significant inhibitory effects on osteoblast differentiation of hMSCs reflected by decreased ALP activity, in vitro mineralization, and downregulation of osteoblast-related gene expression. Similarly, we observed decreased in vivo ectopic bone formation. Global gene expression profiling of BMS-833923-treated compared to vehicle-treated control cells, identified 348 upregulated and 540 downregulated genes with significant effects on multiple signaling pathways, including GPCR, endochondral ossification, RANK-RANKL, insulin, TNF alpha, IL6, and inflammatory response. Further bioinformatic analysis employing Ingenuity Pathway Analysis revealed significant enrichment in BMS-833923-treated cells for a number of functional categories and networks involved in connective and skeletal tissue development and disorders, e.g., NFκB and STAT signaling. Conclusions. We identified SMO/Hedgehog antagonist (BMS-833923) as a powerful inhibitor of osteoblastic differentiation of hMSC that may be useful as a therapeutic option for treating conditions associated with high heterotopic bone formation and mineralization.
Study on Application Effect of Sand Consolidating Agent for the Slope of Highway Subgrade in Season Frozen Zone
Authors: Zhang Dongliang , Yang Guangqing , Niu Xiaodi , Zhang Lu , Wang Zhijie
Published: November 2019

In deep season frozen areas, the solidified layer is easy to be destroyed due to the influence of freeze‐thaw cycles after the surface layer of the sandy slope is solidified by chemical methods. In order to study the application effect of the new sand consolidating agent after solidifying sand body, the mechanism of strength formation was analyzed by scanning electron microscopy (SEM). The freeze‐thaw cycle tests were carried out on sand consolidating samples. The direct shear tests and unconfined compressive strength tests were carried out before and after freeze‐thaw cycles to analyze the freeze‐thaw resistance of sand consolidating samples. The sand consolidation agent was tested on‐site, and its strength was tested to observe its effect. The results showed that the adhesive membranes on the surface of sand particles were formed by the sand consolidating agent, which increased the cohesion and strength of sand particles. After freeze‐thaw cycle tests, the cohesion, internal friction angle, and compressive strength of the solidified sand gradually decreased with increasing freeze‐thaw cycles. The decreasing rate reduced from fast to slow and then tends to be stable. The failure mode of samples changed from brittle failure to plastic failure. The sand consolidating layer can effectively prevent collapse of the sandy slope. Combining with the external‐soil spray seeding, the sand consolidation layer is beneficial to the growth of plants.
En Face Optical Coherence Tomography Imaging Ellipsoid Zone Regeneration in Laser-Induced and Solar Maculopathies
Authors: Gunzinger Jeanne M. , Fasler Katrin , Barthelmes Daniel , Maloca Peter , Hasler Pascal W. , Böni Christian , Zweifel Sandrine A.
Published: November 2019

The purpose of the study was to analyze imaging findings in spectral domain en face optical coherence tomography (SD OCT) in patients with laser‐induced and solar maculopathies focusing on the possible regeneration of the ellipsoid zone. In a retrospective case series of 3 patients (4 eyes) with solar maculopathy and 2 patients (3 eyes) with laser‐induced maculopathy who underwent a comprehensive ocular examination, ellipsoid zone (EZ) was segmented from SD OCT data. Evaluation of EZ in en face OCT revealed a hyporeflective lesion surrounded by a hyperreflective border. The area of EZ alteration was measured manually in en face OCT. All patients showed partial EZ regeneration. Mean EZ alteration decreased from 0.12 mm2 (range: 0.05–0.32) at baseline to 0.07 mm2 (range: 0.01–0.22) at last follow‐up (p=0.018, mean follow‐up: 372 days; range: 115–592). Mean best visual acuity (BVA) improved from 20/36 at baseline to 20/30 (p=0.018). In conclusion, en face OCT imaging clearly delineated the area of EZ alteration in patients with laser‐induced and solar maculopathies. Follow-up showed significant reformation of the EZ as well as improvement of BVA.
HLA-DQB1/DRB1 Alleles Associate with Traditional Chinese Medicine Syndrome of Chronic Hepatitis B: A Potential Predictor of Progression
Authors: Liu Xiyang , Wan Tingjun , Dang Sijie , Wang Dong , Jiang Cen , Su Yue , Shen Mengmeng , Tang Xuchen , Li Xia , Li Baixue , Wen Li , Feng Quansheng
Published: November 2019

Background and Aims. Traditional Chinese medicine (TCM) has been widely applied in chronic hepatitis B (CHB) supplementary treatment in China. Kidney yang deficiency syndrome (KYDS), one of the most common TCM syndromes of CHB, is more likely to progress to liver cirrhosis or hepatocellular carcinoma than other syndromes. Polymorphisms in the human leucocyte antigen- (HLA-) DQB1 and -DRB1 genes were reported to be associated with hepatitis B virus infection outcomes. Here, we investigated whether HLA-DQB1 and HLA-DRB1 are associated with the classification of CHB TCM syndromes. Methods. We genotyped HLA-DQB1 and HLA-DRB1 alleles in a total of 105 subjects, including 74 CHB patients (28 KYDS and 46 non-KYDS) and 31 healthy individuals from Sichuan Province of Southwest China, by polymerase chain reaction sequence-based typing (PCR-SBT). Moreover, a meta-analysis was carried out for further verification. Results. The proportion of patients with high HBV DNA load (≥2000 IU/ml) in the KYDS group is higher than that in the non-KYDS group (60.70% [17/28] vs. 28.30% [13/46]); P=0.01). The frequencies of HLA-DQB1∗02:01 (P=0.04) and HLA-DRB1∗03:01 (P=0.04) in the KYDS group were significantly increased compared to the non-KYDS group. The gene test and meta-analysis showed that HLA-DRB1∗08:03 confers susceptibility to CHB (odds ratio = 1.57). Conclusion. We found an association between HLA-DRB1/DQB1 polymorphisms and KYDS of CHB. Moreover, KYDS patients of CHB are characteristic with high HBV DNA loads. These findings help to reveal the biological mechanism of KYDS in high risk of CHB progression and suggest a potential prognostic value for disease outcome evaluation.
Facility Location with Tree Topology and Radial Distance Constraints
Authors: Adasme Pablo , Firoozabadi Ali Dehghan
Published: November 2019

Let Gd = (V, Ed) be an input disk graph with a set of facility nodes V and a set of edges Ed connecting facilities in V. In this paper, we minimize the total connection cost distances between a set of customers and a subset of facility nodes S⊆V and among facilities in S, subject to the condition that nodes in S simultaneously form a spanning tree and an independent set according to graphs and Gd, respectively, where is the complement of Gd. Four compact polynomial formulations are proposed based on classical and set covering p‐Median formulations. However, the tree to be formed with S is modelled with Miller–Tucker–Zemlin (MTZ) and path orienteering constraints. Example domains where the proposed models can be applied include complex wireless and wired network communications, warehouse facility location, electrical power systems, water supply networks, and transportation networks, to name a few. The proposed models are further strengthened with clique valid inequalities which can be obtained in polynomial time for disk graphs. Finally, we propose Kruskal‐based heuristics and metaheuristics based on guided local search and simulated annealing strategies. Our numerical results indicate that only the MTZ constrained models allow obtaining optimal solutions for instances with up to 200 nodes and 1000 users. In particular, tight lower bounds are obtained with all linear relaxations, e.g., less than 6% for most of the instances compared to the optimal solutions. In general, the MTZ constrained models outperform path orienteering ones. However, the proposed heuristics and metaheuristics allow obtaining near‐optimal solutions in significantly short CPU time and tight feasible solutions for large instances of the problem.
Preoperative β-Blockade with Propranolol Reduces Biomarkers of Metastasis in Breast Cancer: A Phase II Randomized Trial
Authors: Hiller Jonathan G. , Cole Steven W. , Crone Elizabeth M. , Byrne David J. , Shackleford David M. , Pang Jia-Min B. , Henderson Michael A. , Nightingale Sophie S. , Ho Kwok M. , Myles Paul S. , Fox Stephen , Riedel Bernhard , Sloan Erica K.
Published: November 2019

Purpose:

The majority of deaths from breast cancer occur following the development of metastatic disease, a process inhibited by β-blockers in preclinical studies. This phase II randomized controlled trial evaluated the effect of preoperative β-blockade with propranolol on biomarkers of metastatic potential and the immune cell profile within the primary tumor of patients with breast cancer.

Patients and Methods:

In this triple-blind placebo-controlled clinical trial, 60 patients were randomly assigned to receive an escalating dose of oral propranolol (n = 30; 80–160 mg daily) or placebo (n = 30) for 7 days prior to surgery. The primary endpoint investigated the effect of propranolol on prometastatic and proinflammatory gene expression within the primary tumor.

Results:

Propranolol downregulated primary tumor expression of mesenchymal genes (P = 0.002) without affecting epithelial gene expression (P = 0.21). Bioinformatic analyses implicated downregulation of Snail/Slug (P = 0.03), NF-κB/Rel (P < 0.01), and AP-1 (P < 0.01) transcription factors in structuring the observed transcriptome alterations, and identified changes in intratumoral neutrophil, natural killer cell, and dendritic cell recruitment (all P < 0.01). Patients with clinical evidence of drug response (lowered heart rate and blood pressure) demonstrated elevated tumor infiltration of CD68+ macrophages and CD8+ T cells.

Conclusions:

One week of β-blockade with propranolol reduced intratumoral mesenchymal polarization and promoted immune cell infiltration in early-stage surgically-resectable breast cancer. These results show that β-blockade reduces biomarkers associated with metastatic potential, and support the need for larger phase III clinical trials powered to detect the impact of β-blockade on cancer recurrence and survival.

See related commentary by Blaes et al., p. 1781
Development of a Novel Multi-Isoform ALDH Inhibitor Effective as an Antimelanoma Agent
Authors: Dinavahi Saketh S. , Gowda Raghavendra , Gowda Krishne , Bazewicz Christopher G. , Chirasani Venkat R. , Battu Madhu Babu , Berg Arthur , Dokholyan Nikolay V. , Amin Shantu , Robertson Gavin P.
Published: November 2019

The aldehyde dehydrogenases (ALDH) are a major family of detoxifying enzymes that contribute to cancer progression and therapy resistance. ALDH overexpression is associated with a poor prognosis in many cancer types. The use of multi-ALDH isoform or isoform-specific ALDH inhibitors as anticancer agents is currently hindered by the lack of viable candidates. Most multi-ALDH isoform inhibitors lack bioavailability and are nonspecific or toxic, whereas most isoform-specific inhibitors are not effective as monotherapy due to the overlapping functions of ALDH family members. The present study details the development of a novel, potent, multi-isoform ALDH inhibitor, called KS100. The rationale for drug development was that inhibition of multiple ALDH isoforms might be more efficacious for cancer compared with isoform-specific inhibition. Enzymatic IC50s of KS100 were 207, 1,410, and 240 nmol/L toward ALDH1A1, 2, and 3A1, respectively. Toxicity of KS100 was mitigated by development of a nanoliposomal formulation, called NanoKS100. NanoKS100 had a loading efficiency of approximately 69% and was stable long-term. NanoKS100 was 5-fold more selective for killing melanoma cells compared with normal human fibroblasts. NanoKS100 administered intravenously at a submaximal dose (3-fold lower) was effective at inhibiting xenografted melanoma tumor growth by approximately 65% without organ-related toxicity. Mechanistically, inhibition by KS100 significantly reduced total cellular ALDH activity to increase reactive oxygen species generation, lipid peroxidation, and accumulation of toxic aldehydes leading to apoptosis and autophagy. Collectively, these data suggest the successful preclinical development of a nontoxic, bioavailable, nanoliposomal formulation containing a novel multi-ALDH isoform inhibitor effective in the treatment of cancer.
Local Surgery Improves Survival in Patients with Primary Metastatic Breast Cancer: A Population-Based Study
Authors: Zhao Yuan-Yuan , Sun He-Fen , Yang Xue-Li , Zhao Yang , Chen Meng-Ting , Jin Wei
Published: November 2019

The clinical value of local surgery in the breast cancer patients with distant metastasis is still unclear. A total of 8,922 primary metastatic breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed in the current study. Primary outcome variables included breast cancer-specific survival (BCSS) and overall survival (OS). Among the patients, 1,724 (19.3%) who underwent surgical treatment (ST) of primary breast tumor had increased OS (p < 0.001) and BCSS (p < 0.001) compared with those in the nonsurgical treatment (NST) group. Multivariate analysis revealed that surgery improved survival and was an independent prognostic factor for OS (hazard ratio [HR] = 0.617; 95% confidence interval [CI], 0.562–0.676, p < 0.001) and BCSS (HR = 0.623; 95% CI, 0.565–0.686, p < 0.001). Further result showed that ST tended to prolong the survival of patients with 1 or 2 distant metastatic sites (p < 0.05 for OS, p < 0.05 for BCSS). However, no differences were found in prognostic outcomes between different surgical procedure groups (p = 0.886 for OS, p = 0.943 for BCSS). In conclusion,our study suggested that local surgery appeared to confer a survival benefit, which may provide new understanding of treatment for these patients.
Foix-Chavany-Marie Syndrome due to Unilateral Anterior Opercular Damage with Contralateral Infarction of Corona Radiata
Authors: Yoshii Fumihito , Sugiyama Hiromi , Kodama Kazuyuki , Irino Takahito
Published: November 2019

Foix-Chavany-Marie syndrome (FCMS) is a rare type of pseudobulbar palsy characterized by automatic-voluntary dissociation of movements of the face, tongue, pharynx, and masticatory muscles. Most cases are due to bilateral ischemic lesions of the anterior operculum, but the syndrome has also been described after unilateral opercular damage, either isolated or associated with contralateral cortico-nuclear tract involvement. We report a patient with FCMS due to right anterior opercular lesion with contralateral infarction of the corona radiata. The patient presented with paralysis of the face and tongue with automatic and voluntary dissociation. To our knowledge, FCMS with this peculiar lesion topography has rarely been reported. We discuss the underlying mechanism with reference to MRI and diffusion tensor imaging.
Effects of Knowledge of Task on Control of Oral-Nasal Balance in Speech
Authors: Srinivas Varsha , Bressmann Tim
Published: November 2019

Introduction: Previous research has shown that altering the nasal signal level auditory feedback changed the control of oral-nasal balance in normal speakers. The present study investigated whether knowledge of the task and the instruction not to compensate would change the participants’ response to the manipulation. Methods: Twenty participants (10 females) in 2 groups continuously repeated a sentence while their nasal signal level was increased or decreased and fed back to them via headphones, so the speakers heard themselves as more or less nasal, respectively. After the first recording session, participants were debriefed about the true nature of the experiment. They were instructed not to compensate in the second recording session. The outcome measures were the percentage changes of nasalance scores from the first baseline. Results: Statistical analysis using a repeated measures analysis of variance showed an effect of the nasal signal level, F(5,80) = 2.51, p = 0.049, and a nasal signal level by knowledge of task interaction effect, F(5,80) = 3.25, p = 0.019. Post hoc tests showed that the maximum nasal signal level auditory feedback resulted in a significant decrease of nasality from the initial baseline. Conclusion: Despite knowledge of the task, speakers were unable to resist compensating. As found in previous research, there was a numerically higher compensation response at the maximum than at the minimum nasal signal level auditory feedback condition.
Factors Affecting Intermittent Infusion Hemodiafiltration
Authors: Eiki Kenji , Otake Takuya
Published: November 2019

Background: Intermittent infusion hemodiafiltration ­(I-HDF) has been performed for a number of years since this mode of dialysis became available with dialyzers used in Japan. It has been effective in some cases and ineffective in others. In this study, we analyzed and clarified these differences. Summary: We conducted a retrospective study to determine the factors affecting the effectiveness of I-HDF treatment in some patients and ineffectiveness in others and classified the complex causes associated with volume load that were identified. Key Messages: Bolus dialysate infusion in I-HDF affects the volume load (preload), and repeated bolus dialysate infusion influences both preload and afterload in patients with valvular heart disease. In this study, I-HDF was effective when brain natriuretic peptide levels, cardiothoracic ratio, and ultrafiltration rate were well controlled and cardiac load was low. I-HDF was shown to be effective in patients who are prone to developing hypotension at the end of a dialysis session. There were several factors, including different types of load, involved in inefficiency of I-HDF.
Increased Basal Blood Histamine Levels in Patients with Self-Reported Hypersensitivity to Non-Steroidal Anti-Inflammatory Drugs
Authors: Kakolyri Maria , Strikou Flora , Kavallari Andriana , Chliva Caterina , Makris Michael , Tiligada Ekaterini
Published: November 2019

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most prevalent causes of drug hypersensitivity reactions (DHRs), yet the underlying processes are far from clear. Despite the established role of histamine in allergic reactions, its precise implication in DHRs is elusive. Objectives: This study aimed to explore the connection of basal blood histamine levels to the reported NSAID hypersensitivity. Methods: Sixteen patients reporting hypersensitivity reactions to a single or multiple NSAIDs and/or paracetamol and 18 healthy volunteers serving as the normal control group enrolled in the study. The medical history was recorded and histamine was quantified spectrophotofluorometrically in whole peripheral blood and plasma. Results: Compared to the normal group, plasma but not whole blood histamine levels were significantly higher in patients (p < 0.001), mainly in the subgroup reporting hypersensitivity to a single agent (p < 0.001). Plasma histamine levels were significantly correlated with the culprit drug selectivity for cyclooxygenase (COX) isozymes (p < 0.001), with higher levels being obtained in patients reporting reactions to COX-1 than to COX-2 selective inhibitors (p < 0.05). Conclusions: The findings provide first evidence connecting basal blood histamine levels to the reported NSAID-triggered DHRs. Prospective studies are expected to decipher the contribution of histamine-associated parameters to the mechanisms underlying DHRs.
The Presence of Renal IgG Deposits in Necrotizing Crescentic Glomerulonephritis Associated with ANCA Is Not Related to Worse Renal Clinical Outcomes
Authors: Dudreuilh Caroline , Fakhouri Fadi , Vigneau Cécile , Augusto Jean-François , Machet Marie-Christine , Rabot Nolwenn , Chapal Marion , Charpy Vianney , Barbet Christelle , Büchler Matthias , Halimi Jean-Michel , Gatault Philippe
Published: November 2019

Introduction: Classical pauci-immune necrotizing crescentic glomerulonephritis (CGN) associated with antineutrophil cytoplasmic autoantibodies (ANCA) is characterized by the absence of renal immunoglobulin (Ig) deposits. However, IgG deposits can sometimes be present. We wanted to assess whether necrotizing CGN with IgG deposits is associated with a more severe presentation and outcome than necrotizing CGN without IgG deposits. Methods: Between November 2008 and August 2013, we retrospectively identified 158 patients from four centers who had necrotizing CGN due to primary ANCA-associated systemic vasculitis. Glomerular IgG deposits were found in 18 (11%) patients (group 1). For each patient in group 1, we selected 2 patients with classical pauci-immune necrotizing CGN with the nearest date of diagnosis in the same center (group 2, n = 36). We assessed clinical, biological, and pathological characteristics in both groups. Results: Baseline characteristics were similar in both groups, and most patients had ANCA-associated vasculitis with antibodies to myeloperoxidase (74%). Deposits displayed moderate to strong staining in 9 patients. As compared with group 2, group 1 exhibited a higher frequency of interstitial fibrosis/tubular atrophy lesions (p = 0.024) and lower frequency of acute tubular necrosis (p = 0.046). Nevertheless, after a mean follow-up of 30 and 26 months for group 1 and group 2, respectively, IgG deposits did not affect the renal prognosis or probability of relapse. Finally, the groups did not differ in renal or patient survival. Conclusions: IgG deposits, detected in 11% of patients with ANCA-associated necrotizing CGN, did not affect renal or patient outcomes.
The Impact of Regional Variation in Clinical Practice on Thyroid Cancer Diagnosis: A National Population-Based Study
Authors: Decallonne Brigitte , Van den Bruel Annick , Macq Gilles , Elaut Nathalie , De Schutter Harlinde
Published: November 2019

Objective: Regional variation in thyroid cancer incidence in Belgium, most pronounced for low risk cancer, was previously shown to be related to variation in clinical practice, with higher thyroid surgery rates and lower proportions of preoperative fine-needle aspiration (FNA) in regions with high thyroid cancer incidence (period 2004–2006). The objective of this study was to investigate regional thyroid cancer incidence variation in relation with variation in thyroid surgery threshold in a more recent Belgian thyroid cancer cohort. Methods: A population-based cohort of thyroid cancer patients that underwent a (near) total thyroidectomy in the period 2009–2011 (n = 2,329 patients) was identified and studied by linking data from the Belgian cancer registry and the Belgian health insurance companies, and case-by-case study of the pathology protocols. The execution of preoperative FNA and the thyroid resection specimen weight were compared between high and low thyroid cancer incidence regions. Thyroid weight in the pT1a-restricted group was studied as a proxy for surgical threshold for benign nodular goiter. Furthermore, time trend analyses were performed for the execution of FNA for the period 2004–2012. Results: Although a lower proportion of FNA in the high thyroid cancer incidence region persisted in the period 2009–2011 (41.2% [31.9–50.9] vs. 72.9% [64.9–79.7] in the low-incidence region (LIR), p < 0.001), a positive time trend was observed for the period 2004–2012. The median thyroid surgical specimen weight was lower in the high incidence region compared to the LIR (27.0 g [IQR 18.0–45.3] vs. 36.0 g [IQR 22.0–73.0], p < 0.0001), and this finding was corroborated in the pT1a-restricted group. Conclusion: Interregional differences in use of FNA and surgical thyroid specimen weight are consistent with an inverse relation between thyroid cancer incidence and thyroid surgery threshold, carrying risk for overdiagnosis.
Chylous Ascites Accompanying Internal Hernia after Total Gastrectomy with Roux-en-Y Reconstruction
Authors: Koyama Ryota , Maeda Yoshiaki , Minagawa Nozomi , Shinohara Toshiki , Hamada Tomonori
Published: November 2019

We report the case of a 69-year-old man with a history of esophagogastric junction cancer (Barrett’s esophageal cancer; pT1b [SM], N0, M0, pStage IA) that was surgically resected 2 years prior to the present episode. Recurrence was not observed during follow-up. Following complaints of dysphagia and abdominal pain, computed tomography revealed signs of internal hernia. Thus, laparoscopic exploration was performed. Intraoperatively, accumulation of chylous ascites accompanying the internal hernia through the jejunojejunostomy mesenteric defect was observed, which was successfully treated with laparoscopic hernia reduction and defect closure by sutures without intestinal resection. Here, we discuss the case and report that along with previous studies, our study suggests that chylous ascites might be a reliable sign of intestinal viability for herniated intestines.
Sete fadas me fadaram
Authors: Ribeiro Filho Paulo César
Published: November 2019

O mote “Sete fadas me fadaram” tornou-se notório como um dos versos de um rimance popular coligido por Almeida Garrett (1799-1854) e publicado em seu Romanceiro no ano de 1828. Esse mesmo verso aparece como título de uma das faixas do álbum Eu vou ser como a toupeira, do cantor português Zeca Afonso, lançado em 1972. O presente estudo tem por objetivo revisitar a tradição músico-literária fundada por tal mote feérico em suas variantes, reforçando os laços nunca completamente desfeitos entre literatura e música.
Um jogo chamado música, em que não existem ganhadores ou perdedores
Authors: Silva Avani Souza
Published: November 2019

BRITO, Teca Alencar de. Um jogo chamado Música – Escuta, experiência, criação, educação. São Paulo: Peirópolis, 2019.
Música e Literatura: um Fenômeno Unitário
Authors: Tygel Julia
Published: November 2019

Entrevista com o maestro Isaac Karabtchevsky
From the Archetypical Archive to Cultures of Documentation
Authors: Pickett James , Sartori Paolo
Published: November 2019

This essay argues that recent theoretical literature on the archive contains critical insights for studies of Islamic documents, while also pushing to move beyond some of the core assumptions of that same literature. There is no question that the fundamental concerns of an “archival turn” are every bit as relevant to studies of Islamic societies, past and present, as they are to European-dominated ones. Yet investigating Islamic “archives” presents the challenge of coming to terms with a concept—the archive—and an attending set of assumptions and theoretical baggage derived almost exclusively from European history. To address this challenge, we propose that employing the term “cultures of documentation” offers a way of having one’s cake and eating it too. In deploying this expression, we signal that there existed multitudes of textual practices and record-keeping activities in the pre-industrial Islamic world, and that it is possible to move away from “archive” as a term without abandoning the core insights and questions of the historical literature built around it.
Go Out and Reconnect
Authors: Posio Pilvi
Published: November 2019

This article contributes to research on community resilience by discussing the relationship of sense of place and social capital. On 11 March 2011, Japan was struck by the Great East Japan Disaster, also known as the 3.11 disaster, which greatly damaged, if not entirely destroyed, built environments and dislocated pre-disaster community networks. Although researchers have increasingly emphasised the importance of social capital to community resilience, the reconstruction of people–place relations in post-disaster settings has remained understudied. Based on an analysis of data collected during eight months of ethnographic fieldwork on long-term recovery in Yamamoto, Japan, this article explains how locals there have renegotiated social networks and their sense of place during their temporal, spatial, and social reorientation following the disaster. Overall, the findings reveal how community resilience can be characterised by a co-constructive relationship of sense of place and social capital.