bluuebunny/crossref_metadata_2025 huggingface dataset:
Photoplethysmogram-based Cognitive Load Assessment Using Multi-Feature Fusion Model
Authors: Zhang Xiao , Lyu Yongqiang , Qu Tong , Qiu Pengfei , Luo Xiaomin , Zhang Jingyu , Fan Shunjie , Shi Yuanchun
Published: September 2019

Cognitive load assessment is crucial for user studies and human--computer interaction designs. As a noninvasive and easy-to-use category of measures, current photoplethysmogram- (PPG) based assessment methods rely on single or small-scale predefined features to recognize responses induced by people’s cognitive load, which are not stable in assessment accuracy. In this study, we propose a machine-learning method by using 46 kinds of PPG features together to improve the measurement accuracy for cognitive load. We test the method on 16 participants through the classical n-back tasks (0-back, 1-back, and 2-back). The accuracy of the machine-learning method in differentiating different levels of cognitive loads induced by task difficulties can reach 100% in 0-back vs. 2-back tasks, which outperformed the traditional HRV-based and single-PPG-feature-based methods by 12--55%. When using “leave-one-participant-out” subject-independent cross validation, 87.5% binary classification accuracy was reached, which is at the state-of-the-art level. The proposed method can also support real-time cognitive load assessment by beat-to-beat classifications with better performance than the traditional single-feature-based real-time evaluation method.
The Status of Endangered Contact Languages of the World
Authors: Lee Nala H.
Published: September 2019

This article provides an up-to-date perspective on the endangerment that contact languages around the world are facing, with a focus on pidgins, creoles, and mixed languages. While language contact is often associated with language shift and hence language endangerment, languages arising from contact also can and do face the risk of endangerment. Recent observations and studies show that contact languages may be at twice the risk of endangerment and loss compared with noncontact languages. The loss of these languages is highly consequential. The arguments that usually apply to why noncontact languages should be conserved also apply to many of these contact languages. This article highlights recent work on the documentation and preservation of contact languages and suggests that much more can be done to protect and conserve this unique category of languages.
Emerging role of extracellular vesicles in liver diseases
Authors: Malhi Harmeet
Published: September 2019

Extracellular vesicles (EVs) are membrane-defined nanoparticles released by most cell types. The EVs released by cells may differ quantitatively and qualitatively from physiological states to disease states. There are several unique properties of EVs, including their proteins, lipids and nucleic acid cargoes, stability in circulation, and presence in biofluids, which make them a critical vector for cell-to-cell communication and impart utility as a biomarker. EVs may also serve as a vehicle for selective cargo secretion. Similarly, EV cargo may be selectively manipulated for targeted therapeutic delivery. In this review an overview is provided on the EV classification, biogenesis, and secretion pathways, which are conserved across cell types. Next, cargo characterization and effector cell responses are discussed in the context of nonalcoholic steatohepatitis, alcoholic hepatitis, and acetaminophen-induced liver injury. The review also discusses the potential biomarker and therapeutic uses of circulating EVs.
NSAID-induced injury of gastric epithelial cells is reversible: roles of mitochondria, AMP kinase, NGF, and PGE2
Authors: Ahluwalia Amrita , Hoa Neil , Jones Michael K. , Tarnawski Andrzej S.
Published: September 2019

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (DFN) and indomethacin (INDO) are extensively used worldwide. Their main side effects are injury of the gastrointestinal tract, including erosions, ulcers, and bleeding. Since gastric epithelial cells (GEPCs) are crucial for mucosal defense and are the major target of injury, we examined the extent to which DFN- and INDO-induced GEPC injury can be reversed by nerve growth factor (NGF), 16,16 dimethyl prostaglandin E2 (dmPGE2), and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), the pharmacological activator of the metabolic sensor AMP kinase (AMPK). Cultured normal rat gastric mucosal epithelial (RGM1) cells were treated with PBS (control), NGF, dmPGE2, AICAR, and/or NSAID (DFN or INDO) for 1–4 h. We examined cell injury by confocal microscopy, cell death/survival using calcein AM, mitochondrial membrane potential using MitoTracker, and phosphorylation of AMPK by Western blotting. DFN and INDO treatment of RGM1 cells for 2 h decreased mitochondrial membrane potential and cell viability. NGF posttreatment (initiated 1 or 2 h after DFN or INDO) reversed the dissipation of mitochondrial membrane potential and cell injury caused by DFN and INDO and increased cell viability versus cells treated for 4 h with NSAID alone. Pretreatment with dmPGE2 and AICAR significantly protected these cells from DFN- and INDO-induced injury, whereas dmPGE2 and AICAR posttreatment (initiated 1 h after NSAID treatment) reversed cell injury and significantly increased cell viability and rescued the cells from NSAID-induced mitochondrial membrane potential reduction. DFN and INDO induce extensive mitochondrial injury and GEPC death, which can be significantly reversed by NGF, dmPGE2, and AICAR.

NEW & NOTEWORTHY This study demonstrated that mitochondria are key targets of diclofenac- and indomethacin-induced injury of gastric epithelial cells and that diclofenac and indomethacin injury can be prevented and, importantly, also reversed by treatment with nerve growth factor, 16,16 dimethyl prostaglandin E2, and 5-aminoimidazole-4-carboxamide ribonucleotide.
Silencing of long noncoding RNA XIST protects against renal interstitial fibrosis in diabetic nephropathy via microRNA-93-5p-mediated inhibition of CDKN1A
Authors: Yang Jindou , Shen Yan , Yang Xia , Long Yanjun , Chen Shuang , Lin Xin , Dong Rong , Yuan Jing
Published: September 2019

Long noncoding RNAs (lncRNAs) have been reported to play an important role in diabetic nephropathy (DN). However, the molecular mechanism involved in this process remains poorly understood. Thus, the present study aimed to explore the function and molecular mechanism of dysregulated lncRNA X-inactive specific transcript (XIST) in DN. DN mouse models were established by streptozotocin treatment, and human renal tubular epithelial HK-2 cells were exposed to high glucose to produce an in vitro model. XIST was highly expressed in renal tissues of patients with DN, mice with DN, and high glucose-exposed HK-2 cells. To identify the interaction among XIST, miR-93-5p, and cyclin-dependent kinase inhibitor 1A (CDKN1A) and to analyze the functional significance of their interaction in renal interstitial fibrosis, we altered endogenous expression of XIST and miR-93-5p and CDKN1A. Dual-luciferase reporter assay results suggested that XIST was highly expressed in the kidney tissue of DN mice and high glucose-exposed HK-2 cells. XIST was identified to be a lncRNA that could bind to miR-93-5p, and CDKN1A was a target of miR-93-5p. Downregulated expression of XIST led to an increase in miR-93-5p expression, thereby decreasing CDKN1A and suppressing renal interstitial fibrosis in DN. Consistently, XIST knockdown reduced the expression of fibrosis markers (fibronectin, collagen type IV, and transforming growth factor-β1). Restoration of CDKN1A or decreasing miR-93-5p yielded a reversed effect on renal interstitial fibrosis. In conclusion, our study demonstrated that silenced XIST inducing miR-93-5p-dependent CDKN1A inhibition was beneficial for preventing renal interstitial fibrosis in DN, which may provide a future strategy to prevent the progression of DN.
Acid-sensing ion channels blockade attenuates pressor and sympathetic responses to skeletal muscle metaboreflex activation in humans
Authors: Campos Monique O. , Mansur Daniel E. , Mattos João D. , Paiva Adrielle C. S. , Videira Rogerio L. R. , Macefield Vaughan G. , da Nóbrega Antonio C. L. , Fernandes Igor A.
Published: September 2019

In animals, the blockade of acid-sensing ion channels (ASICs), cation pore-forming membrane proteins located in the free nerve endings of group IV afferent fibers, attenuates increases in arterial pressure (AP) and sympathetic nerve activity (SNA) during muscle contraction. Therefore, ASICs play a role in mediating the metabolic component (skeletal muscle metaboreflex) of the exercise pressor reflex in animal models. Here we tested the hypothesis that ASICs also play a role in evoking the skeletal muscle metaboreflex in humans, quantifying beat-by-beat mean AP (MAP; finger photoplethysmography) and muscle SNA (MSNA; microneurography) in 11 men at rest and during static handgrip exercise (SHG; 35% of the maximal voluntary contraction) and postexercise muscle ischemia (PEMI) before (B) and after (A) local venous infusion of either saline or amiloride (AM), an ASIC antagonist, via the Bier block technique. MAP (BAM +30 ± 6 vs. AAM +25 ± 7 mmHg, P = 0.001) and MSNA (BAM +14 ± 9 vs. AAM +10 ± 6 bursts/min, P = 0.004) responses to SHG were attenuated under ASIC blockade. Amiloride also attenuated the PEMI-induced increases in MAP (BAM +25 ± 6 vs. AAM +16 ± 6 mmHg, P = 0.0001) and MSNA (BAM +16 ± 9 vs. AAM +8 ± 8 bursts/min, P = 0.0001). MAP and MSNA responses to SHG and PEMI were similar before and after saline infusion. We conclude that ASICs play a role in evoking pressor and sympathetic responses to SHG and the isolated activation of the skeletal muscle metaboreflex in humans.

NEW & NOTEWORTHY We showed that regional blockade of the acid-sensing ion channels (ASICs), induced by venous infusion of the antagonist amiloride via the Bier block anesthetic technique, attenuated increases in arterial pressure and muscle sympathetic nerve activity during both static handgrip exercise and postexercise muscle ischemia. These findings indicate that ASICs contribute to both pressor and sympathetic responses to the activation of the skeletal muscle metaboreflex in humans.
Controversies in exertional heat stroke diagnosis, prevention, and treatment
Authors: Laitano Orlando , Leon Lisa R. , Roberts William O. , Sawka Michael N.
Published: September 2019

During the past several decades, the incidence of exertional heat stroke (EHS) has increased dramatically. Despite an improved understanding of this syndrome, numerous controversies still exist within the scientific and health professions regarding diagnosis, pathophysiology, risk factors, treatment, and return to physical activity. This review examines the following eight controversies: 1) reliance on core temperature for diagnosing and assessing severity of EHS; 2) hypothalamic damage induces heat stroke and this mediates “thermoregulatory failure” during the immediate recovery period; 3) EHS is a predictable condition primarily resulting from overwhelming heat stress; 4) heat-induced endotoxemia mediates systemic inflammatory response syndrome in all EHS cases; 5) nonsteroidal anti-inflammatory drugs for EHS prevention; 6) EHS shares similar mechanisms with malignant hyperthermia; 7) cooling to a specific body core temperature during treatment for EHS; and 8) return to physical activity based on physiological responses to a single-exercise heat tolerance test. In this review, we present and discuss the origins and the evidence for each controversy and propose next steps to resolve the misconception.
Assessment of the Effect of Oral Health on Quality of Life and Oral-Health Indicators among ESRD Patients in Southwest Florida: A Pilot Study
Authors: Kahar Payal , Chapman Carol , Gupta Jayanta
Published: September 2019

Purpose. To determine and compare OHRQoL (oral-health-related quality of life) using the Geriatric Oral Health Assessment Index (GOHAI-12) and Oral Health Impact Profile (OHIP-14) among patients receiving hemodialysis (HD).Methods. Face-to-face interviews and intraoral examinations were conducted among 70 patients. Mann–WhitneyUtest and Kruskal–Wallis test were used to compare each item score with demographics and dental and overall health status.Results. The mean number of years on dialysis was 4.7 ± 7.5 yrs; the mean number of teeth present was 19.7 ± 11.04; median values of OHRQoL using GOHAI-12 and OHIP-14 were 52 and 64. Within GOHAI-12, limiting food (p0.043), uncomfortable eating in front of people (p0.045), limiting contact with people (p0.046), and eating without discomfort (p0.011) were significantly associated with females. Being worried (p0.040) and self-conscious (p0.048) were significant for age groups ≤65 years. Prevented from speaking was associated with >20 teeth (p0.016). Being worried about oral health was associated with number of years on dialysis (p0.042). Within OHIP-14, speech was associated with number of teeth present (p0.024). Total inability to function was significantly associated with race (p0.018), number of teeth (p0.028), and edentulousness (p0.031).Conclusions. GOHAI-12 was more effective than OHIP-14 in assessing OHRQoL. However, most subjective experiences did not correlate with clinical findings. Systemic health issue like end-stage renal disease affecting QoL might have taken precedence over dental problems. Clinical assessments should be inherent in oral-health evaluation and there should be cooperation between nephrologists and dentists in promoting oral health and treating systemic conditions among HD patients.
Assessment of Knowledge, Attitude, and Practice of Sunlight Exposure of Infants among Mothers Attending in Governmental Health Facilities in Farta District, South Gondar Zone, North West Ethiopia, 2018
Authors: Gedamu Haileyesus , Tafere Yilkal
Published: September 2019

Background. Sunlight exposure serves an important purpose in human bodies. It promotes good health and plays a major role in the production of the very essential vitamin, vitamin D. Vitamin D is important for the growth of healthy, normal bones. Research conducted in different areas suggested that daily exposure to sunshine remains the cheapest, safest, and most effective method of preventing rickets. Objective. To assess knowledge, attitude, and practice of infants to sunlight exposure among lactating women in Farta district, in 2018. Method. Institution based cross sectional study design was conducted among mothers attending the selected health center. Systematic sampling method was used to select individual respondents. Data were entered and analyzed by using SPSS version 20. Result. Among 357 respondents identified for the study, 95% (n=339) was responding to the interview. Of the total respondents, 49.9%, 46%, and 45.7% of them had poor knowledge, unfavorable attitude, and poor practice about sunlight exposure, respectively. Conclusion and recommendation. The results of this study showed that almost half of the mothers had inadequate knowledge, attitude, and inadequate practice about sunlight exposure. Therefore, mothers need to be educated about the importance of sunlight exposure.
Primary Chordoma of the Nasopharynx: A Rare Case Report and Review of the Literatures
Authors: Dwianingsih Ery Kus , Snak Yosinta , Rinonce Hanggoro Tri , Wasita Brian , Antoro Ester Lianawati , Amr Samir S.
Published: September 2019

Primary chordoma of the nasopharynx is an extremely rare malignant tumor of notochordal origin in the extra-osseous axial skeleton. It presents as a soft tissue mass without involvement of the skull base bone (clivus) and may mimic other lesions of the nasopharynx. A 26-year-old male patient is presented with nasal obstruction and congestion for the last 3 years. Physical and radiological examination revealed a mass in the naso-oropharyngeal region. It was suspected to be a cystic mass or abscess on radiological imaging. However, histopathological examination revealed a chordoma. We review all 20 cases of primary nasopharyngeal chordoma reported previously in the literature. Nasopharyngeal chordoma should be considered in the differential diagnosis of nasopharyngeal mass due to its unspecific appearance on clinical and radiology examination.
Effect of Naoxintong Capsules on the Activities of CYP450 and Metabolism of Metoprolol Tartrate in Rats Evaluated by Probe Cocktail and Pharmacokinetic Methods
Authors: Ouyang Huizi , Shen Jiayuan , Huang Xuhua , Ma Wenjuan , Jia Qi , Yao Guangzhe , Tang Zhidan , Zhang Dandan , Sun Mengjie , Teye Azietaku John , Hao Jia , Gao Xiumei , Chang Yanxu , He Jun
Published: September 2019

Naoxintong capsule (NXT), a prescribed Chinese medicine, has been used clinically for more than 20 years and is widely received by patients. We determined five probe drugs, namely, omeprazole (CYP2C19), midazolam (CYP3A4), phenacetin (CYP1A2), tolbutamide (CYP2C9), and dextromethorphan (CYP2D6) to study the potential influences of NXT on the activities of CYP enzymes and assessed the pharmacokinetics effect of NXT on metoprolol tartrate in rat plasma. The study showed that AUC(0–24) and AUC(0–∞) of midazolam (CYP3A4) in NXT coadministration group (283.7 ± 65.2 h·ng·mL−1 and 292.0 ± 75.1 h·ng·mL−1 in group B; 295.7 ± 62.7 h·ng·mL−1 and 299.5 ± 60.0 h·ng·mL−1 in group C) were significantly decreased as compared to another group (416.8 ± 82.3 h·ng·mL−1 and 424.9 ± 77.9 h·ng·mL−1 in group A), while that of dextromethorphan (CYP2D6) showed an opposite tendency (540.7 ± 119.7 h·ng·mL−1 and 595.3 ± 122.2 h·ng·mL−1 in group A, 760.6 ± 184.9 h·ng·mL−1 and 788.7 ± 211.0 h·ng·mL−1 in group B, and 734.3 ± 118.5 h·ng·mL−1 and 757.2 ± 105.4 h·ng·mL−1 in group C). Moreover, NXT preadministration can enhance the metabolism of metoprolol tartrate and reduce the metabolism of O-demethylmetoprolol. The results indicated that NXT had potential effects in inducing CYP3A4 and inhibiting CYP2D6 in the metabolism of metoprolol tartrate. It suggests that patients who coadministered NXT and metoprolol tartrate should be advised of potential herb-drug interactions (HDIs) to reduce therapeutic failure or accelerated toxicity of conventional drug treatment.
Comparison of the Clinical Outcomes between Echelette Extended Range of Vision and Diffractive Bifocal Intraocular Lenses
Authors: Liu Xin , Song Xiaohui , Wang Wei , Zhu Yanan , Lyu Danni , Shentu Xingchao , Chen Peiqing , Yu Yibo , Yao Ke
Published: September 2019

Purpose. To compare the clinical outcomes of echelette extended range of vision (ERV) and diffractive bifocal intraocular lenses (IOLs). Methods. This is a prospective, consecutive, nonrandomized clinical trial. Seventy-three eligible patients (109 eyes) received the implantation of echelette ERV IOL (Tecnis Symfony ZXR00) or diffractive bifocal IOL (Tecnis ZMB00). 1 week, 1 month, and 3 months after surgery, visual acuities at different distances were examined. At 3 months, defocus curves, contrast sensitivities (CSs) with and without glare, optic path difference (OPD) scans, and questionnaires were evaluated. Regression analyses were applied to discover influence factors on postoperative vision. Results. ZXR00 showed better distance (P<0.05) and intermediate (P<0.001) visual acuities, while ZMB00 was better at distance-corrected near visual acuity (P<0.001). Multivariate analyses indicated that worse intermediate (P<0.001) and near vision (P=0.013) of ZMB00 might occur in patients with longer axial length. ZXR00 demonstrated smoother defocus curve and higher CSs. Superior modulation transfer function (MTF) and higher Strehl ratio (P<0.05) were shown in ZXR00. In questionnaire evaluation, ZXR00 received better outcomes in self-reported vision, Visual Function-14 (VF-14) questionnaire, Quality of Vision (QoV) questionnaire, satisfaction, and recommendation grades. Spectacle dependence did not differ between ZXR00 and ZMB00 statistically. Conclusion. ZXR00 proved to be remarkable in distance and intermediate vision, defocus curve smoothness, CSs, and visual comfort, while ZMB00 achieved better near vision. ZXR00 may attain better near vision if postoperative SE remains slightly negative. Patients with relatively longer axial length might receive less favorable intermediate and near vision after ZMB00 implantation. This trial is registered with ChiCTR-ONC-17011119.
Emergency Surgery Mortality (ESM) Score to Predict Mortality and Improve Patient Care in Emergency Surgery
Authors: Tribuddharat Sirirat , Sathitkarnmanee Thepakorn , Sappayanon Pavit
Published: September 2019

Background. Emergency surgery has poor outcomes with high mortality. Numerous studies have reported the risk factors for postoperative death in order to stratify risk and improve perioperative care; nevertheless, a predictive model based upon these risk factors is lacking. Objective. We aimed to identify the risk factors of postoperative mortality and to construct a new model for predicting mortality and improving patient care. Methods. We included adult patients undergoing emergency surgery at Srinagarind Hospital between January 2012 and December 2014. The patients were randomized: 80% to the Training group for model construction and 20% to the Validation group. Patient data were extracted from medical records and then analyzed using univariate and multivariate logistic regression. Results. We recruited 758 patients, and the mortality rate was 14.5%. The Training group comprised 596 patients, and the Validation group comprised 162. Based upon a multivariate analysis in the Training group, we constructed a model to predict postoperative mortality—an Emergency Surgery Mortality (ESM) score based on the coefficient of each risk factor from the multivariate analysis. The ESM score comprised 7 risk factors, i.e., coagulopathy, ASA class 5, bicarbonate <15 mEq/L, heart rate >100/min, systolic blood pressure <90 mmHg, renal comorbidity, and general surgery, for a total score of 11. An ESM score ≥4 was predictive of postoperative mortality with an AUC of 0.83. The respective sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value, and accuracy for an ESM score ≥4 predictive of postoperative mortality was 70.2%, 94.9%, 13.8, 0.3, 69.4%, 95.1%, and 91.4%. The performance of the ESM score in the Validation group was comparable. Conclusions. An ESM score comprises 7 risk factors for a total score of 11. An ESM score ≥4 is predictive of postoperative mortality with a high AUC (0.83), sensitivity (70.2%), and specificity (94.9%). Four risk factors are preoperatively manageable for decreasing the probability of postoperative mortality and improving quality of patient care.
Predictors for New Native-Vessel Occlusion in Patients with Prior Coronary Bypass Surgery: A Single-Center Retrospective Research
Authors: Zheng Ze , Cheng Zi chao , Wang Shao ping , Li Shi ying , Wang Jian , Peng Hong yu , Wu Zheng , Li Wen zheng , Lv Yun , Tian Jia yu , Cheng Shu juan , Liu Jing hua
Published: September 2019

Objectives. Chronic total occlusion (CTO) is prevalent in patients with prior coronary artery bypass grafting (CABG). However, data available concerning the prevalence of new-onset CTO of native vessels in patients with prior CABG is limited. Therefore, the objective of the study is to determine predictors for new native-vessel occlusion in patients with prior coronary bypass surgery. Methods. 354 patients with prior CABG receiving follow-up angiography are selected and analyzed in the present study, with clinical and angiographic variables being analyzed by logistic regression to determine the predictors of new native-vessel occlusion. Results. The overall new occlusion rate was 35.59%, with multiple CTOs (42.06%) being the most prevalent (LAD 24.60% and RCA 18.25%, respectively). Additionally, current smoking (OR: 2.67; 95% CI: 2.60 to 2.74; p=0.01), reduced ejection fraction (OR: 1.76; 95% CI: 1.04 to 2.97; p=0.04), severe stenosis (OR: 3.65; 95% CI: 2.55 to 5.24; p=0.01), and diabetes mellitus (OR: 1.86; 95% CI: 1.34 to 2.97; p=0.04) serve as the independent predictors for new native-vessel occlusion. Conclusion. As to high incidence of postoperative CTO, appropriate revascularization strategies and postoperative management should be taken into careful consideration.
Correlation-Based Ensemble Feature Selection Using Bioinspired Algorithms and Classification Using Backpropagation Neural Network
Authors: Elgin Christo V. R. , Khanna Nehemiah H. , Minu B. , Kannan A.
Published: September 2019

A framework for clinical diagnosis which uses bioinspired algorithms for feature selection and gradient descendant backpropagation neural network for classification has been designed and implemented. The clinical data are subjected to data preprocessing, feature selection, and classification. Hot deck imputation has been used for handling missing values and min-max normalization is used for data transformation. Wrapper approach that employs bioinspired algorithms, namely, Differential Evolution, Lion Optimization, and Glowworm Swarm Optimization with accuracy of AdaBoostSVM classifier as fitness function has been used for feature selection. Each bioinspired algorithm selects a subset of features yielding three feature subsets. Correlation-based ensemble feature selection is performed to select the optimal features from the three feature subsets. The optimal features selected through correlation-based ensemble feature selection are used to train a gradient descendant backpropagation neural network. Ten-fold cross-validation technique has been used to train and test the performance of the classifier. Hepatitis dataset and Wisconsin Diagnostic Breast Cancer (WDBC) dataset from University of California Irvine (UCI) Machine Learning repository have been used to evaluate the classification accuracy. An accuracy of 98.47% is obtained for Wisconsin Diagnostic Breast Cancer dataset, and 95.51% is obtained for Hepatitis dataset. The proposed framework can be tailored to develop clinical decision-making systems for any health disorders to assist physicians in clinical diagnosis.
Fracture of Parallel Strand Bamboo Composite under Mode I Loading: DCB Test Investigation
Authors: Shen Yurong , Huang Dongsheng , Chui Ying Hei , Dai Chunping
Published: September 2019

This paper describes the experimental studies on Mode I fracture of parallel strand bamboo (PSB) by the double cantilever beam (DCB) test. R-curves based on the elementary beam theory and specimen compliance are proposed in order to overcome the difficulties to monitor the crack propagation during experiments. The results demonstrate that the energy release rate (ERR) is influenced by the specimen geometry, i.e., the specimen width and initial crack length. The ERR at the plateau level is similar for the range of the analyzed widths (B = 20, 40, and 60 mm), while it decreases with width increasing up to 80 mm and 100 mm. The energy release rate for PSB specimens would verge to a stable value with the width increasing up to a specific value, while the value of the energy release rate will be influenced by the initial crack length. Consequently, the DCB tests also show that the obtained R-curve in this study is not a material property.
Acute Partial Brown-Séquard Syndrome Secondary to Intraforaminal Disc Prolapse and Spinal Cord Infarction
Authors: Astreinidis Athanasios , Finitsis Stephanos , Mavropoulou Xanthippi , Psoma Elisavet , Prassopoulos Panagiotis
Published: September 2019

We report the case of a 45-year-old female who presented with acute left abdominal pain and subsequently developed a left partial Brown-Séquard syndrome. Spinal fluid, inflammatory and prothrombotic tests were unremarkable. Magnetic resonance showed a left intraforaminal disc prolapse at the T9–T10 level and a hyperintense lesion on T2-weighted images in the left postero-lateral cord at the T8–T9 level with restricted diffusion on DWI imaging. A diagnosis of spinal cord infarction due to compromise of the left T8 thoracic radicular artery was made. The patient was managed conservatively and at the 3 months follow-up, she was ambulant and able to walk small distances without a walker.
Comparative Investigation on Torsional Behaviour of RC Beam Strengthened with CFRP Fabric Wrapping and Near‐Surface Mounted (NSM) Steel Bar
Authors: Askandar Nasih , Mahmood Abdulkareem
Published: September 2019

Many researchers worldwide have extensively used fibre‐reinforced polymer (FRP) strengthening materials and near‐surface mounted (NSM) to enhance the shear and flexural strengths of reinforced concrete (RC) beams. However, studies on torsional strengthening are limited. Although a few studies have focused on torsional strengthening, none of them simultaneously investigated torsion with shear and/or bending moment. This study aims at demonstrating the behaviour of RC beams strengthened with FRP sheets (strips) with different configurations and NSM steel bars with different spacing that was subjected to combined actions of torsion and bending moment and making a comparison between them. Seven beams with a dimension of 15 × 25 × 200 cm were casted. One of the beams was not strengthened; three of them were strengthened with carbon FRP, and the others were strengthened with NSM steel bar. The angle of twist at torque intervals, first cracking torque, ultimate torque, and ultimate twist angle of the conventional and strengthened beams during the testing process are compared. Results show a significant improvement in the torsional performance of RC beams using carbon FRP and NSM steel bar. The test beams that were strengthened with CFRP wrapping showed better enhancement in the ultimate torsional moment as opposed to the beams that were strengthened with NSM steel bar.
Early Enrichment of ESR1 Mutations and the Impact on Gene Expression in Presurgical Primary Breast Cancer Treated with Aromatase Inhibitors
Authors: Leal Mariana Ferreira , Haynes Ben P. , Schuster Eugene , Yeo Belinda , Afentakis Maria , Zabaglo Lila , Martins Vera , Buus Richard , Dodson Andrew , Cheang Maggie C.U. , Smith Ian E. , Martin Lesley-Ann , Dowsett Mitch
Published: September 2019

Purpose:

To investigate the presence of ESR1 mutations in primary estrogen-receptor–positive (ER+) breast cancer treated with extended (>4 weeks) neoadjuvant (presurgical) aromatase inhibitor (NAI) therapy and to identify patients who may gain less benefit from aromatase inhibition (AI) alone based upon on-treatment changes in gene expression.

Experimental Design:

We evaluated ER, progesterone receptor, and Ki67 by immunostaining, ESR1 mutations by droplet-digital PCR and expression of over 800 key breast cancer genes in paired pre- and post-NAI tumor samples from 87 ER+ breast cancer patients.

Results:

Cell proliferation and estrogen-regulated genes (ERG) remained suppressed in most tumors indicative of persistent response to NAI. Enrichment of ESR1 mutations was found in five tumors and predominantly in patients receiving therapy for >6 months. ESR1-mutant tumors showed increased expression of ESR1 transcript and limited suppression of ERGs and proliferation-associated genes in response to NAI. ESR1 wild-type tumors with high residual proliferation (Ki67r ≥10%; 15/87 tumors) showed lower ESR1/ER expression pre- and post-therapy and lower ERGs. Tumors with ESR1 mutations or Ki67r ≥10% showed less inhibition of estrogen response, cell cycle, and E2F-target genes.

Conclusions:

Ligand-independent ER signaling, as a result of ESR1 mutation or reduced ER dependence, identified after extended NAI therapy, can guide early selection of patients who would benefit from combination therapy.
Multispecific Targeting with Synthetic Ankyrin Repeat Motif Chimeric Antigen Receptors
Authors: Balakrishnan Ashwini , Rajan Anusha , Salter Alexander I. , Kosasih Paula L. , Wu Qian , Voutsinas Jenna , Jensen Michael C. , Plückthun Andreas , Riddell Stanley R.
Published: September 2019

Purpose:

The outgrowth of antigen-negative variants is a significant challenge for adoptive therapy with T cells that target a single specificity. Chimeric antigen receptors (CAR) are typically designed with one or two scFvs that impart antigen specificity fused to activation and costimulation domains of T-cell signaling molecules. We designed and evaluated the function of CARs with up to three specificities for overcoming tumor escape using Designed Ankyrin Repeat Proteins (DARPins) rather than scFvs for tumor recognition.

Experimental Design:

A monospecific CAR was designed with a DARPin binder (E01) specific for EGFR and compared with a CAR designed using an anti-EGFR scFv. CAR constructs in which DARPins specific for EGFR, EpCAM, and HER2 were linked together in a single CAR were then designed and optimized to achieve multispecific tumor recognition. The efficacy of CAR-T cells bearing a multispecific DARPin CAR for treating tumors with heterogeneous antigen expression was evaluated in vivo.

Results:

The monospecific anti-EGFR E01 DARPin conferred potent tumor regression against EGFR+ targets that was comparable with an anti-EGFR scFv CAR. Linking three separate DARPins in tandem was feasible and in an optimized format generated a single tumor recognition domain that targeted a mixture of heterogeneous tumor cells, each expressing a single antigen, and displayed synergistic activity when tumor cells expressed more than one target antigen.

Conclusions:

DARPins can serve as high-affinity recognition motifs for CAR design, and their robust architecture enables linking of multiple binders against different antigens to achieve functional synergy and reduce antigen escape.
Impact of FDG PET Imaging for Expanding Patient Eligibility and Measuring Treatment Response in a Genome-Driven Basket Trial of the Pan-HER Kinase Inhibitor, Neratinib
Authors: Ulaner Gary A. , Saura Cristina , Piha-Paul Sarina A. , Mayer Ingrid , Quinn David , Jhaveri Komal , Stone Ben , Shahin Seta , Mann Grace , Dujka Melanie , Bryce Richard , Meric-Bernstam Funda , Solit David B. , Hyman David M.
Published: September 2019

Purpose:

To determine whether FDG PET can expand eligibility in biomarker-selected clinical trials by providing a means to quantitate response in patients with non-assessable disease by RECIST.

Experimental Design:

SUMMIT (NCT01953926) is a multicenter phase II “basket” trial of the Pan-HER kinase inhibitor, neratinib. Patients had advanced ERBB2 (HER2)-mutant solid tumors, ≥1 measurable lesion, preferably defined unidimensionally by RECIST v1.1, or alternatively metabolically by PET Response Criteria (PRC). The primary aim was to determine the proportion of additional breast cancer patients accrued using PRC who would have otherwise been ineligible based on RECIST criteria alone. The secondary aim was to determine the concordance of response versus non-response between RECIST and PRC.

Results:

Eighty-one patients with HER2-mutant metastatic breast cancer were accrued; 77 were evaluable for response by RECIST and/or PRC. 63 (82%) were RECIST-evaluable and 14 (18%) were accrued using PRC alone. Bone-only disease (n = 11; 79%) was the most common reason for classification as non-measurable by RECIST. Twenty-nine patients were accrued and followed using both criteria, of which 25 (86%; 95% confidence interval, 68%–96%) were concordant for response versus non-response as defined by RECIST and PRC.

Conclusions:

PRC allowed patients with non-RECIST measurable disease access to therapy and facilitated more rapid accrual of patients to this trial of a rare biomarker. PRC and RECIST both provided methods of response assessment and were generally concordant. Thus, PRC was useful as a supplement to RECIST criteria. This provides a rationale for including FDG PET measurements in future clinical trials involving rare tumors or rare genomically defined subpopulations of more common cancers.
Co-occurring Alterations in the RAS–MAPK Pathway Limit Response to MET Inhibitor Treatment in MET Exon 14 Skipping Mutation-Positive Lung Cancer
Authors: Rotow Julia K. , Gui Philippe , Wu Wei , Raymond Victoria M. , Lanman Richard B. , Kaye Frederic J. , Peled Nir , Fece de la Cruz Ferran , Nadres Brandon , Corcoran Ryan B. , Yeh Iwei , Bastian Boris C. , Starostik Petr , Newsom Kimberly , Olivas Victor R. , Wolff Alexander M. , Fraser James S. , Collisson Eric A. , McCoach Caroline E. , Camidge D. Ross , Pacheco Jose , Bazhenova Lyudmila , Li Tianhong , Bivona Trever G. , Blakely Collin M.
Published: September 2019

Purpose:

Although patients with advanced-stage non–small cell lung cancers (NSCLC) harboring MET exon 14 skipping mutations (METex14) often benefit from MET tyrosine kinase inhibitor (TKI) treatment, clinical benefit is limited by primary and acquired drug resistance. The molecular basis for this resistance remains incompletely understood.

Experimental Design:

Targeted sequencing analysis was performed on cell-free circulating tumor DNA obtained from 289 patients with advanced-stage METex14-mutated NSCLC.

Results:

Prominent co-occurring RAS–MAPK pathway gene alterations (e.g., in KRAS, NF1) were detected in NSCLCs with METex14 skipping alterations as compared with EGFR-mutated NSCLCs. There was an association between decreased MET TKI treatment response and RAS–MAPK pathway co-occurring alterations. In a preclinical model expressing a canonical METex14 mutation, KRAS overexpression or NF1 downregulation hyperactivated MAPK signaling to promote MET TKI resistance. This resistance was overcome by cotreatment with crizotinib and the MEK inhibitor trametinib.

Conclusions:

Our study provides a genomic landscape of co-occurring alterations in advanced-stage METex14-mutated NSCLC and suggests a potential combination therapy strategy targeting MAPK pathway signaling to enhance clinical outcomes.
Outcome of Regular Inhaled Treatment in GOLD A Chronic Obstructive Pulmonary Disease Patients
Authors: Cho Jaeyoung , Lee Chang-Hoon , Hwang Yong-Il , Lee Jin Hwa , Kim Tae-Hyung , Lee Ji-Hyun , Oh Yeon-Mok , Yoo Kwang Ha , Jung Ki-Suck , Lee Sang-Do ,   on behalf of the KOLD and KOCOSS Investigators
Published: September 2019

Background: The 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends regular bronchodilator therapy in all group A patients with chronic obstructive pulmonary disease (COPD). Objective: The aim of this study was to evaluate whether regular inhaled treatment in group A patients with COPD improves their health outcomes, including exacerbations and symptoms. Methods: We recruited patients from 2 Korean prospective cohorts. Eligible COPD patients had a modified Medical Research Council (mMRC) dyspnea score of <2, a St. George’s Respiratory Questionnaire for COPD (SGRQ-C) total score of <25, and had no more than 1 exacerbation and no hospitalizations during the previous year. Incidence rates of exacerbations and changes in symptom scores were analyzed. Results: After propensity score matching, there were 107 patient pairs, with and without regular inhaled treatment, who were followed up for mean times of 2.6 and 3.1 years, respectively. The incidence rates of exacerbations in those with and without regular treatment were not significantly different (incidence rate ratio 1.24 [95% CI 0.68 to 2.25]). Significant differences in favor of regular treatment were observed at 6 and 12 months for the SGRQ-C total scores (mean between-group difference –4.7 [95% CI –7.9 to –1.6] and –4.8 [95% CI –7.9 to –1.7], respectively). Regular treatment with a long-acting bronchodilator was also associated with significantly better scores on the SGRQ-C (mean between-group difference –5.0 [95% CI –8.6 to –1.4]) compared to no regular treatment at 12 months of follow-up. Conclusions: Regular inhaled treatment in group A patients with COPD was associated with a symptomatic benefit but not with a reduction of exacerbation rates.
Comparison of Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Anxiety/Depression Scale (SAS/SDS) in Evaluating Anxiety and Depression in Patients with Psoriatic Arthritis
Authors: Yue Tao , Li Qiting , Wang Rongsheng , Liu Zhaoyi , Guo Mengru , Bai Fengmin , Zhang Zhanming , Wang Weifeng , Cheng Yahui , Wang Haijun
Published: September 2019

Background: This study aimed to compare the Hospital Anxiety and Depression Scale (HADS) and the Zung Self-Rating Anxiety/Depression Scale (SAS/SDS) in evaluating anxiety and depression in psoriatic arthritis (PsA) patients. Methods: A total of 70 PsA patients were enrolled. Demographic and clinical characteristics were collected after enrollment. HADS-A and SAS were used to evaluate the anxiety of PsA patients, while HADS-D and SDS were used to evaluate the depression of PsA patients. Results: Similar results were observed in detecting the rate of anxiety by HADS-A and SAS (27.1 vs. 21.4%, p = 0.424), and there was no difference in classifying the severity of anxiety by HADS-A and SAS (p = 0.347). The Spearman test also disclosed that HADS-A score was positively associated with SAS score (p <0.001). The rates of depression were similar by HADS-D and SDS (27.1 vs. 40.0%; p = 0.108). However, different results were observed in grading the severity of anxiety by HADS-D and SDS (p = 0.009), and no correlation was observed between HADS-D and SDS scores (p = 0.138). The consumption of time for HADS assessment was shorter than that for SAS/SDS assessment (p < 0.001). In addition, a positive correlation of HADS-A score with patients’ global assessment (PGA) (p = 0.022) and fatigue scores (p = 0.028) was discovered, and HADS-D score was positively associated with PGA score (p = 0.019). SAS or SDS score presented less correlation with clinical features of PsA patients, which illuminated that only SAS score was positively associated with duration of psoriasis (p = 0.030). Conclusion: HADS seems to be a better option for anxiety and depression assessment than SAS/SDS in PsA patients.
Circulating Connective Tissue Growth Factor Is Associated with Diastolic Dysfunction in Patients with Diastolic Heart Failure
Authors: Chi Hongjie , Feng Haijun , Shang Xiangyu , Jiao Jie , Sun Lanlan , Jiang Wei  , Meng Xianchen , Fan Yifan , Lin Xiangmin , Zhong Jiuchang , Yang Xinchun
Published: September 2019

Background: Connective tissue growth factor (CTGF) and transforming growth factor β1 (TGF-β1) are emerging biomarkers for tissue fibrosis. The aim of this study was to investigate the association between circulating CTGF, TGF-β1 levels and cardiac diastolic dysfunction in patients with diastolic heart failure (DHF). Methods: Admitted subjects were screened for heart failure and those with left ventricular (LV) ejection fraction <45% were excluded. Diastolic dysfunction was defined as functional abnormalities that exist during LV relaxation and filling by echocardiographic criteria. Totally 114 patients with DHF and 72 controls were enrolled. Plasma levels of CTGF, TGF-β1, and B-type natriuretic peptide (BNP) were determined. Results: The plasma CTGF and TGF-β1 levels increased significantly in patients with DHF. Circulating CTGF and TGF-β1 levels were correlated with echocardiographic parameter E/e’ and diastolic dysfunction grading in DHF patients. In multivariate logistic analysis, CTGF was significantly associated with diastolic dysfunction (odds ratio: 1.027, p < 0.001). Plasma CTGF (AUC: 0.770 ± 0.036, p < 0.001) and CTGF/BNP (AUC: 0.839 ± 0.036, p < 0.001) showed good predictive power to the diagnosis of DHF. Conclusions: This finding suggested CTGF could be involved in the pathophysiology of diastolic heart failure and CTGF/BNP might have auxiliary diagnostic value on diastolic heart failure.
Defining the Dorsal STN Border Using 7.0-T MRI: A Comparison to Microelectrode Recordings and Lower Field Strength MRI
Authors: Bot Maarten , Verhagen Okker , Caan Matthan , Potters Wouter V. , Dilai Y. , Odekerken Vincent J.J. , Dijk Joke M. , de Bie Rob M.A. , Schuurman P. Richard , van den Munckhof Pepijn
Published: September 2019

Background: 7.0-T T2-weighted MRI offers excellent visibility of the subthalamic nucleus (STN), which is used as a target for deep brain stimulation (DBS) in Parkinson’s disease (PD). A comparison of 7.0-T MRI to microelectrode recordings (MER) for STN border identification has not been performed. Objective: To compare representation of STN borders on 7.0-T T2 MRI with the borders identified during MER in patients undergoing DBS for PD and to evaluate whether STN identification on 7.0-T T2 MRI leads to alterations in stereotactic target planning. Design/Methods: STN border identification was done using volumetric 7.0-T T2 MRI acquisitions. This was compared to the STN borders identified by MER. STN target planning was independently performed by 3 DBS surgeons on T2 imaging using 1.5-, 3.0-, and 7.0-T MRI. Results: A total of 102 microelectrode tracks were evaluated in 19 patients. Identification of the dorsal STN border was well feasible on 7-T T2, whereas the ventral STN was un­distinguishable from the substantia nigra. The dorsal STN border on MRI was located more dorsal than MER in 73% of trajectories. The average distance from MRI to MER border was 0.9 mm (range –4.4 to +3.5 mm). STN target planning showed high correspondence between the 3 field strengths. Conclusion: 7.0-T T2 MRI offers the possibility of easy identification of the dorsal border of the STN. However, higher field strength MRI does not change the planning of the target. Compared to MER, the dorsal border on MRI was located more dorsal in the majority of cases, situating MER activity within STN representation.
Comparison of Activity Budgets, Diet, and Habitat Utilization between Provisioned and Wild Groups of the François’ Langur (Trachypithecus francoisi) in Mayanghe National Nature Reserve, China
Authors: Liu Jie , Bhumpakphan Naris
Published: September 2019

The endangered François’ langur (Trachypithecus francoisi) is only found from southern China to northeastern Vietnam. This study evaluates behavioral differences between provisioned (Ts, 7 individuals) and wild (Tn, 13 individuals) family groups in Mayanghe National Nature Reserve, China. Scan sampling every 5 min for 12 h daily between the months of March 2013 and February 2014 was used to record behaviors in seven categories. Tn exhibited three main feeding periods daily, whereas Ts showed more variable behavioral patterns that relied on provisions. The Tn alpha male showed twice the amount of guarding behavior compared with the Ts alpha male. The proportion of each habitat type utilized differed significantly between Tn and Ts (χ2[4] = 17,131.4, p < 0.01). Additionally, dietary diversity differed between the two groups: Tn fed on 61 plant species, whereas Ts fed on 43 plant species. Tn rarely ate sweet potato and corn other than discarded remnants of human food (0.2% of their total food sources), whereas these foods represented 21.8% of Ts food sources. We compared data for the two troops to understand this species’ activities under human interference, in particular to determine whether provisioning is a suitable strategy for their conservation.