bluuebunny/crossref_metadata_2025 huggingface dataset:
Automatic Parking Controller with a Twin Artificial Neural Network Architecture
Authors: Moon Jaeyoung , Bae Il , Kim Shiho
Published: September 2019

We propose an artificial deep neural network‐ (ANN‐) based automatic parking controller that overcomes a stubborn restriction prevalent in traditional approaches. The proposed ANN learns human‐like control laws for automatic parking through supervised learning from a training database generated by computer‐aided optimizations or real experiments. By learning the relationships between the instantaneous vehicle states and the corresponding maneuver parameters, the proposed twin controller yields lateral and longitudinal maneuvering parameters for executing automatic parking tasks in confined spaces. The proposed automatic parking controller exhibits a twin architecture comprising a main agent and its cloned agent. Before the main agent assumes a maneuvering action, the cloned agent predicts the consequences of the maneuvering action through a Collision Checking and Adjustment (CCA) system. The proposed parking agent operates like a human driver in a manner that is characterized by an unplanned trajectory. In addition, the kinematics of the subject vehicle is not exactly modelled for parking control. The simulation results demonstrate that the proposed twin agent emulates the attributes of a human driver such as adaptive control and determines the consequences of the tentative maneuvering action under varying kinematic models of the subject vehicle. We validate the proposed parking controller by simulating the software‐in‐the‐loop architecture using a PreScan simulator in which the dynamics of the virtual vehicle’s behavior resemble a real vehicle.
A Mathematical Safety Stock Model for DDMRP Inventory Replenishment
Authors: Lee Chan-Ju , Rim Suk-Chul
Published: September 2019

The inventory replenishment method of the demand‐driven materials requirement planning (DDMRP) draws attention from both scholars and practitioners due to its lower average inventory and, simultaneously, lower stockout rate than existing methods. However, the safety stock of DDMRP replenishment uses a subjective guideline, which is different from any existing safety stock formula. The guideline allows the user to subjectively select the parameter values within a certain range, which jeopardizes the consistency of the inventory performance. This paper proposes an alternative safety stock formula for DDMRP replenishment, which is mathematically defined so as to be consistent. Moreover, simulation indicates that the proposed formula outperforms the DDMRP guidelines and existing safety stock formulas in terms of average inventory and stockout rate.
P27 Promotes TGF-β-Mediated Pulmonary Fibrosis via Interacting with MTORC2
Authors: Dai Yu-heng , Li Xiao-qing , Dong Da-peng , Gu Hai-bo , Kong Cheng-ying , Xu Zhihao
Published: September 2019

Pulmonary fibrosis (PF), a progressive and life-threatening pulmonary disease, is the main pathological basis of interstitial lung disease (ILD) which includes the idiopathic pulmonary fibrosis (IPF). No effective therapeutic strategy for pulmonary fibrosis has been established. TGF-β signaling has emerged as the vital regulator of PF; however, the detailed molecular mechanisms of TGF-β in PF were uncertain. In the present study, we proved that inhibition of MTORC2 suppresses the expression of P27 in MRC5 and HLF cells. And in bleomycin-induced PF model, the expression of α-SMA and P27 was upregulated. Moreover, TGF-β application increased the level of α-SMA, vimentin, and P27 in MRC5 and HLF cells. Furthermore, P27 overexpression advanced the cell cycle process and promoted the proliferation of MRC5 and HLF cells. Finally, the rescue experiment showed that MTORC2 knockdown reversed P27 overexpression-induced cell cycle acceleration and proliferation. Thus, our results suggest that P27 is involved in TGF-β-mediated PF, which was regulated by MTORC2, providing a novel insight into the development of PF.
Mechanisms of Metastasis in Colorectal Cancer and Metastatic Organotropism: Hematogenous versus Peritoneal Spread
Authors: Pretzsch E. , Bösch F. , Neumann J. , Ganschow P. , Bazhin A. , Guba M. , Werner J. , Angele M.
Published: September 2019

Metastasis is the major cause of death in patients with colorectal carcinoma (CRC). The most common sites of metastasis are the liver and the peritoneum. Peritoneal carcinomatosis is often considered the end stage of the disease after the tumor has spread to the liver. However, almost half of CRC patients with peritoneal carcinomatosis do not present with liver metastasis. This brings up the question of whether peritoneal spread can still be considered as the end stage of a metastasized CRC or whether it should just be interpreted as a site of metastasis alternative to the liver. This review tries to discuss this question and summarize the current status of literature on potential characteristics in tumor biology in the primary tumor, i.e., factors (transcription factors and direct and indirect E-cadherin repressors) and pathways (WNT, TGF-β, and RAS) modulating EMT, regulation of EMT on a posttranscriptional and posttranslational level (miRNAs), and angiogenesis. In addition to tumor-specific characteristics, factors in the tumor microenvironment, immunological markers, ways of transport of tumor cells, and adhesion molecules appear to differ between hematogenous and peritoneal spread. Factors such as integrins and exosomal integrins, cancer stem cell phenotype, and miRNA expression appear to contribute in determining the metastatic route. We went through each step of the metastasis process comparing hematogenous to peritoneal spread. We identified differences with respect to organotropism, epithelial-mesenchymal transition, angiogenesis and inflammation, and tumor microenvironment which will be further elucidated in this review. A better understanding of the underlying mechanisms and contributing factors of metastasis development in CRC has huge relevance as it is the foundation to help find specific targets for treatment of CRC.
Systematic Review of Herbal Tea (a Traditional Chinese Treatment Method) in the Therapy of Chronic Simple Pharyngitis and Preliminary Exploration about Its Medication Rules
Authors: Li Chengxian , Wu Fucang , Yuan Weiling , Ding Qi , Wang Min , Zhang QingQing , Zhang Ju , Xing Jingyu , Wang Shang
Published: September 2019

Background. Chronic simple pharyngitis (CSP) is a common clinical chronic respiratory inflammation with persistent and intransigent symptoms. We analyzed the clinical data to find the evidence that herbal tea, a traditional Chinese medicine treatment in China, could improve the symptoms of CSP patients in a simple way. Methods. We systematically reviewed the clinical data of randomized controlled treatments from April 2019 and evaluated the results using the improved Jadad scale and the Cochrane bias risk assessment tool. RevMan 5.3 software was used for chart analysis. In addition, we used Excel to conduct frequency statistics on Chinese herbs from included articles and analyze its medication rules. Results. Among the collection of 161 articles, 6 RCTs published in Chinese journals were included in this review. The methodological quality of the treatments was low, and most of them only provide diagnostic criteria. Inclusion and exclusion criteria were not specified, and none of the 6 RCTs used the blind method on the result evaluator. Furthermore, only one RCT evaluated the baseline level variance. For these reasons, we did not make a network meta-analysis. Conclusions. The traditional Chinese herbs involved in herbal tea did have ingredients to alleviate CSP symptoms. However, our research showed that the current research could not draw any credible conclusions on the curative effect of herbal tea, which indicated that the overall level of TCM clinical research needs to be improved to evaluate the efficacy of herbal tea.
A Unique Morphological Phenotype in Chemoresistant Triple-Negative Breast Cancer Reveals Metabolic Reprogramming and PLIN4 Expression as a Molecular Vulnerability
Authors: Sirois Isabelle , Aguilar-Mahecha Adriana , Lafleur Josiane , Fowler Emma , Vu Viet , Scriver Michelle , Buchanan Marguerite , Chabot Catherine , Ramanathan Aparna , Balachandran Banujan , Légaré Stéphanie , Przybytkowski Ewa , Lan Cathy , Krzemien Urszula , Cavallone Luca , Aleynikova Olga , Ferrario Cristiano , Guilbert Marie-Christine , Benlimame Naciba , Saad Amine , Alaoui-Jamali Moulay , Saragovi Horace Uri , Josephy Sylvia , O'Flanagan Ciara , Hursting Stephen D. , Richard Vincent R. , Zahedi René P. , Borchers Christoph H. , Bareke Eric , Nabavi Sheida , Tonellato Peter , Roy Josée-Anne , Robidoux André , Marcus Elizabeth A. , Mihalcioiu Catalin , Majewski Jacek , Basik Mark
Published: September 2019

The major obstacle in successfully treating triple-negative breast cancer (TNBC) is resistance to cytotoxic chemotherapy, the mainstay of treatment in this disease. Previous preclinical models of chemoresistance in TNBC have suffered from a lack of clinical relevance. Using a single high dose chemotherapy treatment, we developed a novel MDA-MB-436 cell-based model of chemoresistance characterized by a unique and complex morphologic phenotype, which consists of polyploid giant cancer cells giving rise to neuron-like mononuclear daughter cells filled with smaller but functional mitochondria and numerous lipid droplets. This resistant phenotype is associated with metabolic reprogramming with a shift to a greater dependence on fatty acids and oxidative phosphorylation. We validated both the molecular and histologic features of this model in a clinical cohort of primary chemoresistant TNBCs and identified several metabolic vulnerabilities including a dependence on PLIN4, a perilipin coating the observed lipid droplets, expressed both in the TNBC-resistant cells and clinical chemoresistant tumors treated with neoadjuvant doxorubicin-based chemotherapy. These findings thus reveal a novel mechanism of chemotherapy resistance that has therapeutic implications in the treatment of drug-resistant cancer.

Implications:

These findings underlie the importance of a novel morphologic–metabolic phenotype associated with chemotherapy resistance in TNBC, and bring to light novel therapeutic targets resulting from vulnerabilities in this phenotype, including the expression of PLIN4 essential for stabilizing lipid droplets in resistant cells.
The Effect of Continuous Positive Airway Pressure on Cerebral and Splanchnic Oxygenation in Preterm Infants
Authors: Zhong Jiayue , Lui Kei , Schindler Timothy
Published: September 2019

Background: Despite the known clinical benefits of continuous positive airway pressure (CPAP) to support preterm infants breathing, there are limited studies that have examined its effect on regional oxygenation. Objectives: This study aimed to investigate how the application of CPAP affects cerebral and splanchnic tissue oxygenation in preterm infants. Methods: A pilot observational study was conducted in infants using near-infrared spectroscopy while off CPAP and on CPAP. Regional cerebral and splanchnic saturations and variability (coefficient of variability; CV) were evaluated. Results: Twenty-six infants (25–37 weeks gestational age at birth) were studied. The mean cerebral oxygenation did not differ with the application of CPAP (80 ± 4.2% without CPAP; 80 ± 1.9% with CPAP), but variability around the mean was less with CPAP (CV 5 vs. 2%, respectively). Mean cerebral fractional oxygen extraction (FOE) increased with CPAP from 0.13 ± 0.06 to 0.17 ± 0.04% (p = 0.002). Splanchnic oxygenation increased significantly from 66 ± 11.6 to 75 ± 9.1% with CPAP (p < 0.001) and also became more stable (CV 13 vs. 7%, respectively). Splanchnic FOE decreased with CPAP from 0.28 ± 0.13 to 0.22 ± 0.10% (p = 0.002). Conclusion: The application of CPAP did not affect mean cerebral oxygenation in this group of preterm and term infants; however, it led to a significant increase in splanchnic oxygenation. These findings highlight the important role that respiratory support may play in maintaining adequate and stable oxygen delivery to vital organs.
Expression of the Voltage-Gated Potassium Channel Kv1.3 in Lesional Skin from Patients with Cutaneous T-Cell Lymphoma and Benign Dermatitis
Authors: Hu Tengpeng , Krejsgaard Thorbjørn , Nastasi Claudia , Buus Terkild Brink , Nansen Anneline , Hald Andreas , Spee Pieter , Nielsen Pia Rude , Blümel Edda , Gluud Maria , Willerslev-Olsen Andreas , Woetmann Anders , Bzorek Michael , Eriksen Jens O. , Ødum Niels , Rahbek Gjerdrum Lise Mette
Published: September 2019

Background: The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by effector memory T cells (TEM) and plays an important role in their activation and proliferation. Mycosis fungoides (MF), the most common subtype of cutaneous T-cell lymphoma (CTCL), was recently proposed to be a malignancy of skin-resident TEM. However, the expression of Kv1.3 in CTCL has not been investigated. Objectives: This study aims to examine the expression of Kv1.3 in situ and in vitro in CTCL. Methods: The expression of Kv1.3 was examined by immunohistochemistry in skin lesions from 38 patients with MF, 4 patients with Sézary syndrome (SS), and 27 patients with benign dermatosis. In 4 malignant T-cell lines of CTCL (Myla2059, PB2B, SeAx, and Mac2a) and a non-malignant T-cell line (MyLa1850), the expression of Kv1.3 was determined by flow cytometry. The proliferation of those cell lines treated with various concentrations of Kv1.3 inhibitor ShK was measured by 3H-thymdine incorporation. Results: Half of the MF patients (19/38) displayed partial Kv1.3 expression including 1 patient with moderate Kv1.3 positivity, while the other half (19/38) exhibited Kv1.3 negativity. An almost identical distribution was observed in patients with benign conditions, that is, 44.4% (12/27) were partially positive for Kv1.3 including 1 patient with moderate Kv1.3 positivity, while 55.6% (15/27) were Kv1.3 negative. In contrast, 3 in 4 SS patients displayed partial Kv1.3 positivity including 2 patients with weak staining and 1 with moderate staining, while 1 in 4 SS patients was Kv1.3 negative. In addition, all malignant T-cell lines, and a non-malignant T-cell line, displayed low Kv1.3 surface expression with a similar pattern. Whereas 2 cell lines (PB2B and Mac2a) were sensitive to Kv1.3 blockade, the other 2 (Myla2059 and SeAx) were completely resistant. Conclusions: We provide the first evidence of a heterogeneous Kv1.3 expression in situ in CTCL lesions.
Sleep Disorders and Cognitive Impairment in Peritoneal Dialysis: A Multicenter Prospective Cohort Study
Authors: Zhao Youlu , Zhang Yuhui , Yang Zhikai , Wang Jinwei , Xiong Zuying , Liao Jinlan , Hao Li , Liu Guiling , Ren Yeping , Wang Qin , Duan Liping , Zheng Zhaoxia , Dong Jie
Published: September 2019

Background: Patients with chronic kidney disease experience a high burden of sleep disorders, and there are associations between sleep disorders and cognitive impairment. Objectives: Based on our previous cross-sectional survey on cognitive impairment in peritoneal dialysis, we further explored the relationship between sleep disorders and cognitive impairment, and predictors for declining cognitive function. Method: We conducted a multicenter prospective cohort study enrolling 458 clinically stable patients on peritoneal dialysis who were then followed up for 2 years.Demographic data, comorbidities, depression, and biochemistry data were collected at baseline. Sleep disorders including insomnia, restless legs syndrome, sleep apnea syndrome, excessive daytime sleepiness, possible narcolepsy, sleep walking and nightmares, and possible rapid eye movement behavior disorders were assessed using a panel of specific sleep questionnaires at baseline and in a second survey. Global cognitive function was measured at baseline and in a second survey, using the Modified Mini-Mental State Examination. Specific cognitive domains were evaluated using Trail-Making Test Forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status were used to asses immediate and delayed memory, visuospatial skills, and language ability. Results: Sleep disorders were common among peritoneal dialysis patients. The prevalence of cognitive impairment evaluated by the Modified Mini-Mental State Examination (3MS) increased from 19.8 to 23.9%. Possible narcolepsy was associated with decreased Modified Mini-Mental State Examination scores at baseline. During follow-up, sleepwalking and nightmares were associated with higher risks of declined delayed memory in the longitudinal study. Conclusions: Possible narcolepsy was associated with general cognitive dysfunction, and sleep walking and nightmares were risk factors for impaired delayed memory.
Relationship of Serum Bicarbonate Levels with 1-Year Graft Function in Kidney Transplant Recipients in Switzerland
Authors: Wiegand Anna , Graf Nicole , Bonani Marco , Frey Diana , Wüthrich Rudolf P. , Mohebbi Nilufar
Published: September 2019

Background: Metabolic acidosis (MA) is common in kidney transplant recipients (KTRs). Several studies have shown that MA is involved in the progression of chronic kidney disease. However, it is unclear if there is also a relationship between serum bicarbonate and graft function after kidney transplantation (KTx). We hypothesized that low serum bicarbonate is associated with a lower estimated glomerular filtration rate (eGFR) 1 year after KTx. Methods: We performed a post hoc analysis of a single-center, open-label randomized trial in 90 KTRs and investigated the relationship of serum bicarbonate and graft function in the first year after KTx. Results: Prevalence of MA was high after KTx (63%) and decreased to 28% after 1 year. Bicarbonate (20.6 ± 3.0 to 22.7 ± 2.7 mmol/L) increased in the first year after transplantation whereas eGFR (53.4 ± 15.8 to 56.9 ± 18.5 mL/min/1.73 m2) did not change significantly. Higher serum bicarbonate (p = 0.029) was associated with higher eGFR in the first year after KTx. Conclusion: Prevalence of MA is high in KTRs. In the first year after KTx, serum bicarbonate was positively correlated with eGFR, suggesting a potential role of MA in kidney graft function.
The Effect of S-Adenosylmethionine Treatment on Neurobehavioral Phenotypes in Lesch-Nyhan Disease: A Case Report
Authors: Momosaki Ken , Kido Jun , Matsumoto Shiro , Taniguchi Atsuo , Akiyama Tomoyuki , Sawada Takaaki , Ozasa Shiro , Nakamura Kimitoshi
Published: September 2019

Lesch-Nyhan disease (LND) is an X-linked recessive disorder caused by a deficiency in hypoxanthine-guanine phosphoribosyl transferase. Patients with LND experience involuntary movements, including dystonia, choreoathetosis, opisthotonos, ballismus, and self-injury. Alleviating these involuntary movements is important to improve the quality of life in patients with LND. Many clinicians have difficulty controlling these involuntary movements in their patients, and there are no established and effective treatments. A 6-month-old boy with LND presented with generalized dystonia and self-injury behavior that was alleviated after receiving S-adenosylmethionine (SAMe). His self-injury behavior completely resolved after he received SAMe and risperidone. Although he had often experienced inspiratory stridor because of laryngeal dystonia and frequently developed aspiration pneumonitis and bronchitis, no inspiratory stridor was noted after SAMe treatment. The patient is continuing to receive SAMe and risperidone. SAMe treatment alleviates dystonic movements and improves quality of life in pediatric patients with LND. Additional research is needed to determine the long-term safety and efficacy of SAMe and its appropriate dosage.
Evaluation of the Usefulness and Convenience of the Kyoto Classification of Gastritis in the Endoscopic Diagnosis of the Helicobacter pylori Infection Status
Authors: Sakae Hiroyuki , Iwamuro Masaya , Okamoto Yuki , Obayashi Yuka , Baba Yuki , Hamada Kenta , Gotoda Tatsuhiro , Abe Makoto , Kono Yoshiyasu , Kanzaki Hiromitsu , Kawano Seiji , Kawahara Yoshiro , Tanaka Takehiro , Yanai Hiroyuki , Okada Hiroyuki
Published: September 2019

Background/Aims: The Kyoto Classification of Gastritis was published in 2014. Although this classification is now widely used in Japan, its usefulness and convenience have not been sufficiently evaluated. This study aimed to evaluate the usefulness and convenience of this classification in the endoscopic diagnosis of Helicobacter pylori infection. Methods: We made a test for the endoscopic diagnosis of H. pylori infection comprising 30 cases who had representative endoscopic features of non-, active, or inactive gastritis. Thirty-eight participants took the test before and after a brief mini-lecture on the Kyoto Classification of Gastritis. Eighteen participants took the test again 3 months later. We investigated the accuracy before, just after, and 3 months after the mini-lecture. Results: The accuracy of endoscopists after the lecture was significantly improved in comparison to before the lecture (77.6 vs. 83.3%). Medical students also showed significantly improved accuracy after the lecture (56.7 vs. 71.7%). Among endoscopists, this improvement was maintained after 3 months. Before the lecture, the accuracy of diagnosing non-gastritis was 90.3%; it tended to be further improved 3 months later (96.5%). A >10% point increase was observed in diagnosing active (72.7–83.3%) and inactive gastritis (73.2–84.3%) at 3 months after the lecture in comparison to before the lecture. Conclusion: A brief mini-lecture on the Kyoto Classification of Gastritis improved the accuracy in the endoscopic diagnosis of gastritis, indicating that understanding this classification is useful for the prompt diagnosis of H. pylori infection during esophagogastroduodenoscopy.
Histologic Features of Secondary Syphilis
Authors: Liu Xiao Ke , Li Jun
Published: September 2019

Background: Secondary syphilis is a sexually transmitted infection, which is referred to as “the great imitator” and has a wide spectrum of clinical manifestations. As a result, it is essential to identify potential secondary syphilis patients with ambiguous clinical manifestation through pathology. Objective: We sought to analyze the pathological features of secondary syphilis. Methods: We analyzed 59 biopsy specimens from 56 patients with secondary syphilis. Cases were classified according to the histological characteristics and clinical features. Results: Necrotic keratinocytes could be observed in 39 of 59 (66.1%) secondary specimens. Plasma cells (86.4%) were the most common finding overall. The presence of Treponema pallidum was detected mostly at the dermal-epidermal junction. There was no statistical significance between pathological features and age, HIV status, or RPR titer. Conclusions: Necrotic keratinocytes are one of the characteristics of secondary syphilis. The combination of plasma cells, irregular acanthosis, elongated rete ridges, and endothelial swelling should increase the likelihood of syphilis.
Atherogenesis in the Carotid Artery with and without Interrupted Blood Flow of Two Hyperlipidemic Mouse Strains
Authors: Zhao Jian , Huangfu Chaoji , Chang Zhihui , Grainger Andrew T. , Liu Zhaoyu , Shi Weibin
Published: September 2019

Purpose: Atherosclerosis in the carotid arteries is a common cause of ischemic stroke. We examined atherogenesis in the left carotid artery with and without interrupted blood flow of C57BL/6 (B6) and C3H-Apoe-deficient (Apoe–/–) mouse strains. Methods: Blood flow was interrupted by ligating the common carotid artery near its bifurcation in one group of mice and another group was not interrupted. Results: Without interference with blood flow, C3H-Apoe–/– mice developed no atherosclerosis in the carotid artery, while B6-Apoe–/– mice formed advanced atherosclerotic lesions (98,019 ± 10,594 μm2/section) after 12 weeks of a Western diet. When blood flow was interrupted by ligating the common carotid artery near its bifurcation, C3H-Apoe–/– mice showed fatty streak lesions 2 weeks after ligation, and by 4 weeks fibrous lesions had formed, although they were smaller than in B6-Apoe–/– mice. Neutrophil adhesion to endothelium and infiltration in lesions was observed in ligated arteries of both strains. Treatment of B6-Apoe–/– mice with antibody against neutrophils had little effect on lesion size. Conclusions: These findings demonstrate the dramatic influences of genetic backgrounds and blood flow on atherogenesis in the carotid artery of hyperlipidemic mice.
The Legacy of Charles David Marsden: A Role Model in the Field of Movement Disorders
Authors: Zubko Luis Eduardo Borges de Macedo , Franco Matheus Kahakura Pedro , Meira Alex Tiburtino , Germiniani Francisco Manoel Branco , Camargo Carlos Henrique Ferreira , Teive Hélio Afonso Ghizoni
Published: September 2019

David Marsden was one of the most renowned neuroscientists of the twentieth century. His scientific contributions in the specialty of movement disorders are recognized worldwide, particularly in the area of Parkinson’s disease and also in hyperkinesias, such as dystonia and myoclonus.
Treatment Outcome in Patients with Primary or Secondary Transformed Indolent B-Cell Lymphomas
Authors: Demirdas Sedat , Hense Jörg , Dührsen Ulrich , Hüttmann Andreas
Published: September 2019

Background: Histologic transformation (HT) of indolent B-cell lymphomas into an aggressive form can occur simultaneously (primary HT, pHT) or sequentially after a preceding diagnosis of indolent lymphoma (secondary HT, sHT). The clinical course after diagnosis of HT is variable. Objectives: To describe the outcome of treatment in pHT and sHT patients. Methods: We retrospectively analyzed HT cases with an underlying follicular lymphoma, nodal marginal zone lymphoma, extranodal marginal zone lymphoma, lymphoplasmacytic lymphoma, or small lymphocytic lymphoma at our institution. Kaplan-Meier estimates were used to calculate progression-free survival (PFS) and overall survival (OS). Results: Ninety-two HT patients were identified, 38 with pHT and 54 with sHT. In sHT, time-to-transformation was not influenced by the preceding treatment strategy of the indolent lymphoma component. In pHT, median PFS was 61 months (95% CI 27–61), and OS was not reached. In sHT, median PFS and OS was 14 months (95% CI 9–32) and 42 months (95% CI 16–90), respectively. Significant differences between pHT and sHT in PFS (p = 0.002; Hazard ratio [HR] 2.30, 95% CI 1.36–3.91) and OS (p = 0.0001; HR 3.30, 95% CI 1.81–6.03) were observed. Response to treatment for transformation was highly prognostic of PFS and OS (p < 0.0001). Conclusions: The outcome in pHT cases is favorable and signifi­cantly better than in sHT cases. Failure to achieve a remission after treatment for transformation confers a dismal pro­gnosis.
Effects of a Voice Training Program on Acoustics, Vocal Use, and Perceptual Voice Parameters in Catalan Teachers
Authors: Gassull Cecília , Godall Pere , Polini Erica , Amador Miquel , Casanova Cori
Published: September 2019

Objectives: To assess the effect of EVES (Education for a Healthy and Efficient Voice), a voice training program aimed at promoting the use of an efficient and healthy voice in teachers. Sample and Method: Twenty-two teachers in the city of Granollers (Catalonia, Spain) were included in this research. The effect of the EVES program was evaluated focusing on the analysis of physiologic parameters on the one side (stroboscopy analysis), and on perceptual parameters on the other (Q-EVES questionnaire, Voice Handicap Index-10 [VHI-10], and GRBAS [Grade, Roughness, Breathiness, Asthenia, Strain Scale]). Results: The teachers incorporated the vocal strategies in their professional life and reported that the perception of difficulty in using their voice decreased. We observed a significant improvement in VHI-10 markers, in voice management abilities in the classroom, in perceptive and subjective voice parameters, and in some functional lesions. Conclusions: The results suggest that the educational intervention model may have a positive effect on teachers’ vocal care.
Distinct Roles of ROCK1 and ROCK2 on the Cerebral Ischemia Injury and Subsequently Neurodegenerative Changes
Authors: Lu Weizhuo , Wen Jiyue , Chen Zhiwu
Published: September 2019

Cerebral ischemic injury is one of the main causes of adult disability and death. Although significant progress has been made, cerebral ischemia continues to be a major risk to public health worldwide. The Rho kinase (ROCK) signaling pathway has been reported to be significantly involved in many mechanisms of cerebral injury. Although ROCK is ubiquitously expressed in all tissues, ROCK2 subtype expression in brain and the spinal cord is more abundant and improves with age. This makes it a promising target for new therapeutic approaches. In this article, we review the current knowledge on the involvement of ROCK in cerebral ischemia injury and neurodegenerative changes after cerebral injury. After a detailed description of the mechanism of ROCK involvement in axonal regeneration and synaptic function, different roles of ROCK1 and ROCK2 in neurons under physiological and pathological conditions are compared and discussed. In addition, different functions of genetic and pharmacological inhibitions of ROCK1 and ROCK2 on cerebral injury are discussed.
A Case of Multi-System Langerhans Cell Histiocytosis with Local Invasion of the Orbital Apex
Authors: Yamada Hiroko , Kurimoto Takuji , Mori Sotaro , Sakamoto Mari , Ueda Kaori , Yamada-Nakanishi Yuko , Uozumi Yoichi , Shose Hiroyasu , Taniguchi Masaaki , Toyoda Masanori , Minami Hironobu , Nakamura Makoto
Published: September 2019

Langerhans cell histiocytosis (LCH) is characterised by tissue destruction caused by the abnormal proliferation of pathogenic dendritic cells. We report a rare case of multi-system LCH with local invasion of the orbital apex.A 56-year-old woman suffered from a decrease of visual acuity in the left eye caused by central scotoma and the limitation of eye movement in all directions. Magnetic resonance imaging revealed an enhanced lesion in the left orbital apex, suggesting optic nerve compression. She had been diagnosed with eosinophilic granuloma 24 years previously. Two weeks after the current presentation, we admitted the patient for optic canal and orbital apex decompression and subtotal tumour resection. Histopathological analysis confirmed the diagnosis of LCH. Post-surgical treatment with low-dose cytarabine was initiated for the residual tumour. However, it was ceased because of myelosuppression-induced pyelonephritis. After surgery, the central scotoma disappeared on day 5 and eye movement palsy resolved by 6 months. After the cessation of cytarabine, she has received low-dose steroid therapy for 2 years with no recurrence. Early surgical intervention with low-dose steroid therapy can lead to recovery of visual acuity and resolve eye movement palsy in patients with lesions of the orbital apex caused by multi-system LCH.
Impact of Dual versus Single Antiplatelet Therapy on Major Cardiovascular Outcomes in Patients with Acute Coronary Syndrome in the Arabian Gulf
Authors: Al-Zakwani Ibrahim , Al-Lawati Jawad , Alsheikh-Ali Alawi A. , Almahmeed Wael , Rashed Wafa , Al-Mulla Arif , Zubaid Mohammad
Published: September 2019

Objective: To evaluate the association of dual versus single antiplatelet therapy with major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) in the Arabian Gulf. Subjects and Methods: Data were analyzed from 3,559 patients with a diagnosis of ACS admitted to 29 hospitals in 4 Arabian Gulf countries (Bahrain, Kuwait, Oman, and United Arab Emirates) from January 2012 to January 2013. Dual antiplatelet therapy (DAPT), consisting of aspirin and clopidogrel, was compared to aspirin alone. MACE included 12-months cumulative stroke/transient ischemic attack (TIA), myocardial infarction (MI), all-cause mortality, and readmissions for cardiac reasons, post discharge. Analyses were performed using multivariable logistic regression. Results: A total of 74% (n = 2,634) of the patients were on DAPT. At 12-month follow-up, patients on DAPT were significantly less likely to experience MACE events (adjusted OR [aOR] 0.73; 95% CI: 0.61–0.86; p < 0.001). Lower cardiovascular (CV) event rates were also consistent across the following MACE components; MI (aOR 0.66; 95% CI: 0.49–0.88; p = 0.005), all-cause mortality (aOR 0.69; 95% CI: 0.51–0.94; p = 0.018), and readmissions for cardiac reasons (aOR 0.79; 95% CI: 0.66–0.95; p = 0.011). Conversely, DAPT was adversely associated with increased risk of stroke/TIA (aOR 1.68; 95% CI: 1.05–2.69; p = 0.030). Conclusions: DAPT, compared to aspirin therapy alone, was generally associated with better CV outcomes after an ACS event. However, DAPT was adversely associated with increased risk of stroke/TIA in ACS patients in the Arabian Gulf.
Endothelial β-Catenin Signaling Supports Postnatal Brain and Retinal Angiogenesis by Promoting Sprouting, Tip Cell Formation, and VEGFR (Vascular Endothelial Growth Factor Receptor) 2 Expression
Authors: Martowicz Agnieszka , Trusohamn Marta , Jensen Nina , Wisniewska-Kruk Joanna , Corada Monica , Ning Frank Chenfei , Kele Julianna , Dejana Elisabetta , Nyqvist Daniel
Published: September 2019

Objective:

Activation of endothelial β-catenin signaling by neural cell-derived Norrin or Wnt ligands is vital for the vascularization of the retina and brain. Mutations in members of the Norrin/β-catenin pathway contribute to inherited blinding disorders because of defective vascular development and dysfunctional blood-retina barrier. Despite a vital role for endothelial β-catenin signaling in central nervous system health and disease, its contribution to central nervous system angiogenesis and its interactions with downstream signaling cascades remains incompletely understood.

Approach and Results:

Here, using genetically modified mouse models, we show that impaired endothelial β-catenin signaling caused hypovascularization of the postnatal retina and brain because of deficient endothelial cell proliferation and sprouting. Mosaic genetic analysis demonstrated that endothelial β-catenin promotes but is not required for tip cell formation. In addition, pharmacological treatment revealed that angiogenesis under conditions of inhibited Notch signaling depends upon endothelial β-catenin. Importantly, impaired endothelial β-catenin signaling abrogated the expression of the VEGFR (vascular endothelial growth factor receptor)-2 and VEGFR3 in brain microvessels but not in the lung endothelium.

Conclusions:

Our study identifies molecular crosstalk between the Wnt/β-catenin and the Notch and VEGF-A signaling pathways and strongly suggest that endothelial β-catenin signaling supports central nervous system angiogenesis by promoting endothelial cell sprouting, tip cell formation, and VEGF-A/VEGFR2 signaling.
Force Sensing by Piezo Channels in Cardiovascular Health and Disease
Authors: Beech David J. , Kalli Antreas C.
Published: September 2019

Mechanical forces are fundamental in cardiovascular biology, and deciphering the mechanisms by which they act remains a testing frontier in cardiovascular research. Here, we raise awareness of 2 recently discovered proteins, Piezo1 and Piezo2, which assemble as transmembrane triskelions to combine exquisite force sensing with regulated calcium influx. There is emerging evidence for their importance in endothelial shear stress sensing and secretion, NO generation, vascular tone, angiogenesis, atherosclerosis, vascular permeability and remodeling, blood pressure regulation, insulin sensitivity, exercise performance, and baroreceptor reflex, and there are early suggestions of relevance to cardiac fibroblasts and myocytes. Human genetic analysis points to significance in lymphatic disease, anemia, varicose veins, and potentially heart failure, hypertension, aneurysms, and stroke. These channels appear to be versatile force sensors, used creatively to inform various force-sensing situations. We discuss emergent concepts and controversies and suggest that the potential for new important understanding is substantial.
Outcomes and Resource Utilization Associated With Readmissions After Atrial Fibrillation Hospitalizations
Authors: Tripathi Byomesh , Atti Varunsiri , Kumar Varun , Naraparaju Vamsidhar , Sharma Purnima , Arora Shilpkumar , Wojtaszek Ewelina , Gopalan Radha , Siontis Konstantinos C. , Gersh Bernard J. , Deshmukh Abhishek
Published: September 2019

Background

Atrial fibrillation is the most common arrhythmia worldwide. Data regarding 30‐day readmission rates after discharge for atrial fibrillation remain poorly reported.

Methods and Results

The Nationwide Readmission Database (2010–2014) was queried using the
International Classification of Diseases, Ninth Revision
(
ICD‐9
) codes to identify study population. Incidence, etiologies of 30‐day readmission and predictors of 30‐day readmissions, and cost of care were analyzed. Among 1 723 378 patients who survived to discharge, 249 343 (14.4%) patients were readmitted within 30 days. Compared with the readmitted group, the nonreadmitted group had higher utilization of electrical cardioversion and catheter ablation. Atrial fibrillation was the most common cause of readmission (24.1%). Median time to 30‐day readmission was 13 days. Advancing age, female sex, and longer stay during index hospitalization predicted higher 30‐day readmissions, whereas private insurance, electrical cardioversion, catheter ablation, higher income, and elective admissions correlated with lower 30‐day readmission. Comorbidities such as heart failure, neurological disorder, chronic obstructive pulmonary disease, diabetes mellitus, chronic kidney disease, chronic liver failure, coagulopathy, anemia, peripheral vascular disease, and electrolyte disturbance, correlated with increased 30‐day readmissions and cost burden. Trend analysis showed a progressive decline in 30‐day readmission rates from 14.7% in 2010 to 14.3% in 2014 (
P
trend, <0.001).

Conclusions

Approximately 1 in 7 patients were readmitted within 30 days of discharge, with symptomatic atrial fibrillation being the most common cause. We identified a predictive model for increased risk of readmissions and treatment expense. Electrical cardioversion during index admission was associated with a significant reduction in 30‐day readmissions and service charges. The 30‐day readmissions correlated with a substantial rise in the cost of care.
Association of Acute Venous Thromboembolism With In‐Hospital Outcomes of Coronary Artery Bypass Graft Surgery
Authors: Panhwar Muhammad S. , Ginwalla Mahazarin , Kalra Ankur , Gupta Tanush , Kolte Dhaval , Khera Sahil , Bhatt Deepak L. , Sabik Joseph F.
Published: September 2019

Background

While venous thromboembolism (VTE) prophylaxis is a strong recommendation after most surgeries, it is controversial in cardiac surgeries such as coronary artery bypass grafting (CABG), because of perceived low VTE incidence and increased bleeding risk. Prior studies may not have been adequately powered to study outcomes of VTE in this population. We sought to investigate the postoperative incidence and outcomes of CABG patients using a large national inpatient database.

Methods and Results

We utilized the 2013 to 2014 National Inpatient Sample to identify all patients >18 years of age who underwent CABG (without concomitant valvular procedures), and had VTE during the hospital stay. We then compared clinically relevant outcomes in patients with and without VTE. We identified 331 950 CABG procedures. Of these, 1.3% (n=4205) had VTE. Patients with VTE were more likely to be older (mean 67.2±10.4 years versus 65.2±10.4 years,
P
<0.001). VTE was associated with higher incidence of inpatient mortality (6.8% versus 1.7%; adjusted odds ratio 1.92 [95% CI 1.40–2.65];
P
<0.001) and complications. VTE was also associated with higher cost (mean±SE $81 995±$923 versus $48 909±$55) and longer length of stay (mean±SE 17.06±0.16 days versus 8.52±0.01 days).

Conclusions

Our analysis of >330 000 CABG procedures suggests that while postoperative VTE after CABG is rare, it is associated with increased morbidity and mortality. Randomized controlled trials are needed to identify optimal strategies for VTE prophylaxis in these patients.
Viscous Effects in the Solid Earth Response to Modern Antarctic Ice Mass Flux: Implications for Geodetic Studies of WAIS Stability in a Warming World
Authors: Powell E. , Gomez N. , Hay C. , Latychev K. , Mitrovica J. X.
Published: September 2019

The West Antarctic Ice Sheet (WAIS) overlies a thin, variable-thickness lithosphere and a shallow upper-mantle region of laterally varying and, in some regions, very low (~1018 Pa s) viscosity. We explore the extent to which viscous effects may affect predictions of present-day geoid and crustal deformation rates resulting from Antarctic ice mass flux over the last quarter century and project these calculations into the next half century, using viscoelastic Earth models of varying complexity. Peak deformation rates at the end of a 25-yr simulation predicted with an elastic model underestimate analogous predictions that are based on a 3D viscoelastic Earth model (with minimum viscosity below West Antarctica of 1018 Pa s) by ~15 and ~3 mm yr−1 in the vertical and horizontal directions, respectively, at sites overlying low-viscosity mantle and close to high rates of ice mass flux. The discrepancy in uplift rate can be reduced by adopting 1D Earth models tuned to the regional average viscosity profile beneath West Antarctica. In the case of horizontal crustal rates, adopting 1D regional viscosity models is no more accurate in recovering predictions that are based on 3D viscosity models than calculations that assume a purely elastic Earth. The magnitude and relative contribution of viscous relaxation to crustal deformation rates will likely increase significantly in the next several decades, and the adoption of 3D viscoelastic Earth models in analyses of geodetic datasets [e.g., Global Navigation Satellite System (GNSS); Gravity Recovery and Climate Experiment (GRACE)] will be required to accurately estimate the magnitude of Antarctic modern ice mass flux in the progressively warming world.
The Profound Nonsense of Consumer Welfare Antitrust
Authors: Vaheesan Sandeep
Published: September 2019

Despite being the prevailing wisdom, consumer welfare antitrust rests on a bed of nonsense. First, consumer welfare antitrust is built on false history and a rewriting of legislative intent. Second, it relies on a false conception of the market and submerges the state construction of the economy. Third, it depends on, and is informed by, false assumptions about business conduct. While the third falsehood suggests an analytical renovation and better antitrust economics are sorely needed, the first two falsehoods show that empirical improvements are necessary but not enough. These falsehoods together mean that the entire enterprise at present is built on a bed of sand and that a fundamental reconstruction of antitrust is required. An antitrust that promotes an equitable economy and protects democratic institutions will be true to legislative intent, recognize the state construction of the marketplace, and informed by empiricism.
Antitrust Standing after Apple v. Pepper: Application to the Sports Betting Data Market
Authors: Rodenberg Ryan M.
Published: September 2019

In Apple v. Pepper, the U.S. Supreme Court expressed a largely permissive view about whether certain potential plaintiffs have legal standing to pursue antitrust lawsuits in federal court. The Apple v. Pepper ruling provided important clarity about the scope of the so-called indirect purchaser rule set forth forty-plus years earlier in Illinois Brick. This paper first summarizes the key takeaways from the Apple v. Pepper decision released on May 13, 2019, positioning the ruling vis-à-vis other standing-related cases that have sometimes closed the courtroom doors to plaintiffs alleging anticompetitive conduct under the Sherman Act and Clayton Act. This paper then applies the lessons from Apple v. Pepper to sports betting data, an emerging tech-focused market. This paper concludes by outlining how—and why—this market will likely be subject to antitrust scrutiny soon.
What Drives Herding Behavior in Online Ratings? The Role of Rater Experience, Product Portfolio, and Diverging Opinions
Authors: Sunder Sarang , Kim Kihyun Hannah , Yorkston Eric A.
Published: September 2019

Consumers’ postpurchase evaluations have received much attention due to the strong link between ratings and sales. However, less is known about how herding effects from reference groups (i.e., crowd and friends) unfold in online ratings. This research examines the role of divergent opinions, rater experience, and firm product portfolio in attenuating/amplifying herding influences in online rating environments. Applying robust econometric techniques on data from a community of board gamers, we find that herding effects are significant and recommend a more nuanced view of herding. Highlighting the role of rater experience, the positive influence of the crowd is weakened and friend influences are amplified as the rater gains experience. Furthermore, divergent opinions between reference groups create herding and differentiation depending on the reference group and the rater’s experience level. Finally, firms can influence online opinion through their product portfolio in profound ways. A broad and deep product portfolio not only leads to favorable quality inferences but also attenuates social influence. Implications for online reputation management, rating system design, and firm product strategy are discussed.
The Management of Elderly Prisoners in France
Authors: Combalbert Nicolas , Rambourg Cecile
Published: September 2019

Very few studies have examined the mental disorders of elderly prisoners and the difficulties related to their management. For this study, 40 prison workers were interviewed (custodial staff, social workers, and probation officers) to assess staff professional practices and approaches in managing elderly inmates. Findings showed highly ambivalent attitudes to the age-related vulnerabilities of elderly incarcerees, at both emotional and professional levels. Staff attempts to make the incarcerated elderly conform to some four traditional images of the prisoner roles (enemy/citizen/threat/user) may lead some prison staff to use emotional defense mechanisms.