bluuebunny/crossref_metadata_2025 huggingface dataset:
Further improvement on bounds for L-functions related to GL(3)
Authors: Sun Haiwei , Ye Yangbo
Published: March 2019

Let [Formula: see text] be a fixed self-dual Hecke–Maass form for [Formula: see text], and let [Formula: see text] be an even Hecke–Maass form for [Formula: see text] with Laplace eigenvalue [Formula: see text], [Formula: see text]. A subconvexity bound for [Formula: see text] is improved to [Formula: see text], and a subconvexity bound for [Formula: see text] is improved to [Formula: see text]. New techniques employed include an application of an asymptotic formula by Salazar and Ye [Spectral square moments of a resonance sum for Maass forms, Front. Math. China 12(5) (2017) 1183–1200] to make error terms negligible, an iterative algorithm to locate stationary point, and a non-trivial estimation of Kloosterman sums.
Climate Change and Domestic Migration in China
Authors: YANG Junhe
Published: March 2019

This paper constructs theoretical and empirical models to investigate, under the influences of China’s hukou policy, the relationship between spikes in temperatures and temporary migrations of Chinese rural residents. Applying weather data from both the provincial and county levels, the paper first demonstrates the negative impacts of extremely high temperatures on agricultural production. Then, using a fixed effect model, and applying an individual-level panel dataset, which includes information from more than 30,000 Chinese rural residents, the paper shows that the likelihood of a rural resident’s future choice to work outside his or her village increases when crop yields decrease. This result confirms the hypothesis built in the paper’s utility maximization theoretical model of an individual rural resident. To mitigate the risks brought about by disaster-induced agricultural production decreases, the paper proposes reforms of, and improvements in existing agricultural policy insurance services.
Respiratory Capacity and Reserve Predict Cell Sensitivity to Mitochondria Inhibitors: Mechanism-Based Markers to Identify Metformin-Responsive Cancers
Authors: Teh Jing Tsong , Zhu Wan Long , Newgard Christopher B. , Casey Patrick J. , Wang Mei
Published: March 2019

Metformin has been extensively studied for its impact on cancer cell metabolism and anticancer potential. Despite evidence of significant reduction in cancer occurrence in diabetic patients taking metformin, phase II cancer trials of the agent have been disappointing, quite possibly because of the lack of molecular mechanism-based patient stratification. In an effort to identify cancers that are responsive to metformin, we discovered that mitochondria respiratory capacity and respiratory reserve, which vary widely among cancer cells, correlate strongly to metformin sensitivity in both the in vitro and in vivo settings. A causal relationship between respiratory function and metformin sensitivity is demonstrated in studies in which we lowered respiratory capacity by either genetic knockdown or pharmacologic suppression of electron transport chain components, rendering cancer cells more vulnerable to metformin. These findings led us to predict, and experimentally validate, that metformin and AMP kinase inhibition synergistically suppress cancer cell proliferation.
Reduction of Muscle-Invasive Tumors by Photodynamic Therapy with Tetrahydroporphyrin-Tetratosylat in an Orthotopic Rat Bladder Cancer Model
Authors: Berndt-Paetz Mandy , Schulze Philipp , Stenglein Philipp C. , Weimann Annett , Wang Qiang , Horn Lars-Christian , Riyad Yasser M. , Griebel Jan , Hermann Ralf , Glasow Annegret , Stolzenburg Jens-Uwe , Neuhaus Jochen
Published: March 2019

Photodynamic therapy (PDT) is a promising option for minimal-invasive treatment of bladder cancer. Efficacy of PDT in muscle-invasive urothelial cancer is still hampered by low tissue penetration of most photosensitizers due to short excitation wavelength. The novel light reactive agent tetrahydroporphyrin-tetratosylat (THPTS) is excitable at near-infrared (760 nm), allowing tissue penetration of up to 15 mm. Here, we established an orthotopic rat bladder cancer model and examined the effects of THPTS-PDT on tumor growth in vivo, and analyzed molecular mechanisms in vitro. We examined pharmacokinetics and subcellular localization, and evoked cell death mode in cultured rat urothelial carcinoma cells (AY-27). We used female F344 Fischer rats for in vivo studies. Ten rats each were used for THPTS-PDT and light-only control. Bladders were evaluated by macroscopy and histology. Temperature-dependent THPTS uptake resulted in endosomal/lysosomal localization. PDT (0–50 μmol/L THPTS; 10 J/cm2) induced early onset of apoptosis leading to dose-dependent cytotoxicity in AY-27 cells. Single-time transurethral THPTS-PDT (100 μmol/L THPTS; 10 J/cm2) in F344 rats led to significant reduction of muscle-invasive tumor number (2/10 vs. 7/10 in controls) and total tumor volume (60% reduction) 2 weeks after PDT, while sparing healthy tissue. Here, we report for the first time effective tumor growth control by PDT in vivo. THPTS is a promising new photosensitizer with the advantage of higher therapeutic depth and the potential of high-selective therapy in muscle-invasive urothelial cancer. This approach possibly allows minimal-invasive bladder preserving treatment of bladder cancer without systemic side effects.
Targeting Apoptosis: A New Paradigm for the Treatment of Estrogen Receptor–Positive Breast Cancer
Authors: Drago Joshua Z. , Chandarlapaty Sarat , Jhaveri Komal
Published: March 2019

Standard treatment for estrogen receptor–positive metastatic breast cancer involves antiestrogen therapy used alone or in combination with inhibitors of CDK4/6 or mTOR; this approach works mechanistically by eliciting and reinforcing cell-cycle arrest. In this issue, Lok and colleagues diverge from this paradigm by combining the BCL2 inhibitor venetoclax with tamoxifen in a phase Ib clinical trial, building on preclinical work to demonstrate that targeting apoptosis could represent a promising new strategy in the treatment of breast cancer.

See related article by Lok et al., p. 354.
The Significance of Circulating Tumour Cells in the Clinic
Authors: Abalde-Cela Sara , Piairo Paulina , Diéguez Lorena
Published: March 2019

Background: Despite the hype about circulating tumour cells (CTCs) in the early 2000s and their potential in the diagnosis of metastasis, in recent years, the hope for personalised cancer management relies more on circulating tumour (ct)DNA that has entered the clinic in a much more efficient way. So far, approved methods for CTCs in the clinic only provide the counting of CTCs, which enables monitoring of the progression of metastatic breast, prostate, and colorectal cancer patients with therapy. Approved methods for ctDNA facilitate the analysis of specific mutations in lung cancer, thereby providing indications for potentially successful treatments. This situation inclined the balance towards molecular analysis in liquid biopsy, leveraged by new technologies and companies providing broader mutation and gene expression analysis towards the early diagnosis of cancer. Study Design: We conducted a search for the studies published to date that provide details about the significance of CTCs in the clinic. Results: Many studies and clinical trials have demonstrated the potential of CTCs in patient screening, early diagnosis, therapy resistance, and patient prognosis. Conclusions: Large multi-centre studies are still needed to formally validate the clinical relevance of CTCs. Meticulous design of the clinical trials is a crucial point to achieve this long-sought objective.
Seizure Susceptibility Correlates with Brain Injury in Male Mice Treated with Hypothermia after Neonatal Hypoxia-Ischemia
Authors: McNally Melanie A. , Chavez-Valdez Raul , Felling Ryan J. , Flock Debra L. , Northington Frances J. , Stafstrom Carl E.
Published: March 2019

Hypoxic-ischemic encephalopathy is a common neonatal brain injury associated with significant morbidity and mortality despite the administration of therapeutic hypothermia (TH). Neonatal seizures and subsequent chronic epilepsy are frequent in this patient population and current treatments are partially effective. We used a neonatal murine hypoxia-ischemia (HI) model to test whether the severity of hippocampal and cortical injury predicts seizure susceptibility 8 days after HI and whether TH mitigates this susceptibility. HI at postnatal day 10 (P10) caused hippocampal injury not mitigated by TH in male or female pups. TH did not confer protection against flurothyl seizure susceptibility at P18 in this model. Hippocampal (R2 = 0.33, p = 0.001) and cortical (R2 = 0.33, p = 0.003) injury directly correlated with seizure susceptibility in male but not female pups. Thus, there are sex-specific consequences of neonatal HI on flurothyl seizure susceptibility in a murine neonatal HI model. Further studies are necessary to elucidate the underlying mechanisms of sex dimorphism in seizure susceptibility after neonatal HI.
Paraneoplastic opsoclonus-myoclonus syndrome secondary to melanoma metastasis form occult primary cancer
Authors: Mondragón Jaime D. , Jiménez-Zarazúa Omar , Vélez-Ramírez Lourdes N. , Martínez-Rivera María Andrea , Enríquez-Maciel Samnir , González-Guzmán Jesús , Alvarez-Delgado Martha Mercedes , González-Carrillo Pedro Luis
Published: March 2019

Introduction: Opsoclonus-myoclonus syndrome (OMS) is an inflammatory neurological disorder, often requiring a prompt medical evaluation. Among the diverse etiologies associated with OMS are autoimmune, infectious, paraneoplastic, and systemic diseases, and drug intoxication. Clinical Summary: The case of a 36-year-old female with a disabling holocranial headache, sudden loss of consciousness, aggressive behavior, vertigo, and a personal history of somatoform disorder and major depression is presented here. After hospital admission, the patient developed sudden stereotyped movements in all four extremities and oculogyric crises compatible with OMS. Cerebrospinal fluid analysis, viral and autoimmune assays, as well as blood, urine, and bronchial secretion cultures, drug metabolite urinalysis, and tumor markers were all negative. Furthermore, brain computed tomography (CT) and brain magnetic resonance imaging, along with thoraco-abdominopelvic CT and electroencephalography, were also all negative. The patient suffered type one respiratory insufficiency after 72 h of hospitalization, requiring an endotracheal tube. After 13 days the patient suffered cardiac arrest. Necropsy was performed reporting lymph nodes with a poorly differentiated malignant neoplastic lesion, HMB-45, melan-A, vimentin, and S-100 positive, compatible with melanoma metastasis from an occult primary cancer. Discussion: While the incidence of melanoma of unknown primary is between 2.6 and 3.2%, with a median overall survival ranging between 24 and 127 months, when melanoma patients develop OMS their survival is markedly decreased. Although only 5 cases of paraneoplastic OMS secondary to melanoma have been reported in the literature, all had a poor prognosis, dying within 8 months of OMS onset.
A Case of Eosinophilic Chronic Rhinosinusitis Associated with Choroidal Folds and Ocular Motility Disorder
Authors: Ikeda Masahiro , Iwahashi Chiharu , Hirai Takashi , Hattori Kenji , Mitarai Keiichi
Published: March 2019

We report a case of eosinophilic chronic rhinosinusitis (ECRS) associated with choroidal folds and ocular motility disorder. A 50-year-old male with rhinosinusitis and bronchial asthma presented with anorthopia of the lower visual field and ocular motility disorder of the left eye. Dilated fundus examination and optical coherence tomography (OCT) revealed wavy choroidal folds in the upper retina. An emergent computed tomography (CT) showed sinusitis, a partial defect of the superior wall of the orbit on the left side, and deformation of the left eye. Based on the clinical findings, the patient was diagnosed with sinusitis complicated by ocular motility disorder. Endoscopic sinus surgery (ESS) was performed. A histopathological examination of the excised polyps showed extensive eosinophil invasion. According to the clinical findings of the nasal polyps, CT images, and peripheral blood tests, he was diagnosed as ECRS. One month after ESS, both ocular movement and anorthopia were improved. The choroidal folds observed using OCT disappeared 2 months after ESS. Although ECRS is rarely associated with ocular complications, bone involvement in sinusitis may result in deformation of the eyeball leading to choroidal folds and ocular motility disorder.
Transcranial Direct Current Stimulation Improves Pusher Phenomenon
Authors: Yamaguchi Takuya , Satow Takeshi , Komuro Taro , Mima Tatsuya
Published: March 2019

An 83-year-old man suffered from cerebral infarction of the right middle cerebral artery territory. In association with severe left hemiparesis and hemispatial neglect on the left side, he showed severe pusher phenomenon (PP), which made rehabilitation difficult. Transcranial direct current stimulation (tDCS) was applied to the parietal area (2 mA × 20 min/day; anode on the right and cathode on the left) for 8 days, which resulted in remarkable improvement of PP and caused prolongation of static sitting time. tDCS of the parietal area could be a novel treatment option of PP following stroke.
Genotype-Clinical Correlations in Polycystic Kidney Disease with No Apparent Family History
Authors: Sekine Akinari , Fujimaru Takuya , Hoshino Junichi , Suwabe Tatsuya , Oguro Masahiko , Mizuno Hiroki , Kawada Masahiro , Sumida Keiichi , Hiramatsu Rikako , Hasegawa Eiko , Yamanouchi Masayuki , Hayami Noriko , Mandai Shintaro , Chiga Motoko , Kikuchi Hiroaki , Ando Fumiaki , Mori Takayasu , Sohara Eisei , Uchida Shinichi , Sawa Naoki , Takaichi Kenmei , Ubara Yoshifumi
Published: March 2019

Background: Genetic characteristics of polycystic kidney disease (PKD) patients without apparent family history were reported to be different from those with a positive family history. However, the clinical course of PKD patients with no apparent family history is not well documented in the literature. Methods: We evaluated the relationship between genotype and the clinical course of 62 PKD patients with no apparent family history. Results: The annual decline of renal function was faster in the patients with PKD1/PKD2 mutation (PKD1 truncating [–3.08; 95% CI –5.30 to –0.87, p = 0.007], PKD1 nontruncating [–2.10; –3.82 to –0.38, p = 0.02], and PKD2 [–2.31; –4.40 to –0.23, p = 0.03]) than in the other patients without PKD1/PKD2 mutation. Similar results were obtained after adjustment for gender, age, estimated glomerular filtration rate (eGFR), height-adjusted total kidney volume (TKV), and mean arterial pressure (MAP). There was no significant difference in the annual decline of renal function among the different PKD1/PKD2 groups, but Kaplan-Meier analysis showed that progression to eGFR < 15 mL/min/1.73 m2 was significantly faster in PKD1 truncating group (p = 0.05). The annual rate of TKV increase was larger in the patients with PKD1/PKD2 mutation (PKD1 truncating [4.63; 95% CI 0.62–8.64, p = 0.03], PKD1 nontruncating [3.79; 0.55–7.03, p = 0.02], and PKD2 [2.11; –1.90 to 6.12, p = 0.29]) than in the other patients without PKD1/PKD2 mutation. Similar results were obtained after adjustment for gender, age, eGFR, and MAP. Conclusion: Detection of PKD1/PKD2 mutation, especially PKD1 truncating, is useful for predicting the renal outcome and rate of TKV increase in PKD patients with no apparent family history.
Localized Cutaneous Adverse Event Induced by Anastrozole as Adjuvant Treatment for Breast Cancer: A Case Report
Authors: Tanaka Aya , Yamashita Chigusa , Hinogami Haruna , Shirai Hirohiko , Yamamura Jun , Ito Ryota
Published: March 2019

Cutaneous adverse events caused by aromatase inhibitors have been reported to be rare. We describe a rare case of a cutaneous adverse event that developed in a cancer-affected breast after aromatase inhibitor treatment. A 72-year-old postmenopausal female patient who was diagnosed with stage IA breast cancer received anastrozole as adjuvant treatment. Six months after the initiation of anastrozole, she developed an irregularly shaped purpuric plaque with several purpuric papules surrounding the postoperative scar on her left breast. Histological findings revealed capillary vessel proliferation and expansion, with hemorrhage in the superficial dermis. Immunohistochemistry of the skin biopsy specimen revealed hormone receptor expression limited to the vascular endothelial cells of the proliferating and expanding vessels. We believe that anastrozole induced a change in the local estrogen level, which affected the hormone receptor-positive endothelial cells in the dermis near the primary lesion of the breast cancer and caused a cutaneous adverse event only in the aforementioned area.
Complete Response to Chemotherapy against the Recurrence of Neuroendocrine Carcinoma of the Breast in the Anterior Mediastinal Lymph Nodes of a Patient on Hemodialysis: A Case Report
Authors: Chikuie Emi , Yanagawa Senichiro , Tanji Hidehiro , Kodama Shinya , Takeshima Yukio , Sumimoto Kazuo
Published: March 2019

In general, the cancer-bearing rate of patients on dialysis is considered to be higher than that of healthy individuals. There is no established chemotherapy regimen for patients on hemodialysis (HD), but some reports have described chemotherapy administration in such patients according to HD conditions, residual renal function, and the drug metabolic pathway. We present a case involving a 76-year-old female patient on HD who underwent chemotherapy for mediastinal lymph node recurrence of neuroendocrine carcinoma of the breast (NECB) using 5-fluorouracil, epirubicin, and cyclophosphamide (FEC 100) and docetaxel (DTX). The patient showed a complete response to the treatment and survived longer than expected. This is the first report demonstrating a complete response to chemotherapy for the recurrence of primary NECB with the patient having survived for a long time after treatment.
Comparison of Duodenal Mucosal Chromogranin-A Expression in Non-Alcoholic Fatty Pancreas Dyspeptic Patients with and without Endosonography-Diagnosed Early Chronic Pancreatitis: A Case Series Study
Authors: Huang Chung-Tsui , Liang Yao-Jen
Published: March 2019

Nonalcoholic fatty pancreas (NAFP) is hypothetically related to progressive fibro-inflammation of the pancreas whose exocrine function is controlled by enteroendocrine cells (EEC). There is little evidence of pancreatic fibrosis in fatty pancreas and of whether there are quantitative differences for EEC. This study aimed to prove the coexistence of NAFP and pancreatic fibrosis or early chronic pancreatitis (ECP) using acoustic radiation force impulse (ARFI) and endosonography. Besides, the expression of duodenal mucosal chromogranin-A, a surrogate for EEC, was analyzed. Dyspeptic patients were surveyed at the digestive clinic and received abdominal sonography, endosonography, and serology tests. Cases with organic causes of dyspepsia were excluded. Pancreatic fibrosis was defined as an ARFI value ≥1.3 m/s. ECP was defined by at least 2 scores of the Japan Pancreas Society endosonographic criteria. During endosonography, 4 biopsy samples of mucosa in the duodenal first part were obtained for analysis of chromogranin-A expression by Western blot. Mucosal biopsy was also performed at the gastric antrum for surveillance of Helicobacter pylori. Between January and June 2018, a total of 24 patients with NAFP were enrolled among 48 candidates and divided into 2 groups based on whether they had pancreatic fibrosis or not. In the pancreatic fibrosis group (n = 11, pancreatic ARFI: 1.76 ± 0.34 m/s), there was a higher endosonographic criteria score (2.45 vs. 1.61, p = 0.002), increased expression of chromogranin-A (p = 0.001), and more severe fatty pancreas that was defined by pancreatic duct blurring on abdominal sonography (91 vs. 46%, p = 0.062) as compared to the non-pancreatic fibrosis group (n = 13, pancreatic ARFI: 1.11 ± 0.09 m/s). A total of 54 endosonographic abnormalities of ECP was present in these 24 patients in the head (52%), body (31%), and tail (17%), an anatomic pattern similar to pancreatic adenocarcinoma. In conclusion, among dyspeptic patients with NAFP, the duodenal mucosa chromogranin-A showed increased expression in those with pancreatic fibrosis and endosonography-diagnosed ECP.
Insomnia and Dysautonomia with Contactin-Associated Protein 2 and Leucine-Rich Glioma Inactivated Protein 1 Antibodies: A “Forme Fruste” of Morvan Syndrome?
Authors: Bakırcıoğlu-Duman Ezgi , Acar Zeynep , Benbir Gülçin , Yüceer Hande , Acar Hürtan , Baştan Birgül , Petek-Balcı Belgin , Karadeniz Derya , Çokar Özlem , Tüzün Erdem
Published: March 2019

Morvan syndrome (MoS) is typically characterized by neuromyotonia, sleep dysfunction, dysautonomia, and cognitive dysfunction. However, MoS patients with mild peripheral nerve hyperexcitability (PNH) or encephalopathy features have been described. A 46-year-old woman presented with a 2-month history of constipation, hyperhidrosis, and insomnia. Neurologic examination revealed muscle twitching and needle electromyography showed myokymic discharges in all limbs. No clinical or electrophysiological features of neuromyotonia were present. Although the patient denied any cognitive symptoms, neuropsychological assessment revealed executive dysfunction, while other cognitive domains were preserved. Cranial and spinal MRIs were unrevealing and tumor investigation proved negative. Polysomnography examination revealed total insomnia, which was partially reversed upon immune-modulatory therapy. Investigation of a broad panel of antibodies revealed serum leucine-rich glioma inactivated protein 1 and contactin-associated protein 2 antibodies. The features of this case indicate that the presentation of PNH syndromes may show significant variability and that MoS patients may not necessarily exhibit full-scale PNH and encephalopathy symptoms.
Fibroblast Primary Cilia Are Required for Cardiac Fibrosis
Authors: Villalobos Elisa , Criollo Alfredo , Schiattarella Gabriele G. , Altamirano Francisco , French Kristin M. , May Herman I. , Jiang Nan , Nguyen Ngoc Uyen Nhi , Romero Diego , Roa Juan Carlos , García Lorena , Diaz-Araya Guillermo , Morselli Eugenia , Ferdous Anwarul , Conway Simon J. , Sadek Hesham A. , Gillette Thomas G. , Lavandero Sergio , Hill Joseph A.
Published: March 2019

Background:

The primary cilium is a singular cellular structure that extends from the surface of many cell types and plays crucial roles in vertebrate development, including that of the heart. Whereas ciliated cells have been described in developing heart, a role for primary cilia in adult heart has not been reported. This, coupled with the fact that mutations in genes coding for multiple ciliary proteins underlie polycystic kidney disease, a disorder with numerous cardiovascular manifestations, prompted us to identify cells in adult heart harboring a primary cilium and to determine whether primary cilia play a role in disease-related remodeling.

Methods:

Histological analysis of cardiac tissues from C57BL/6 mouse embryos, neonatal mice, and adult mice was performed to evaluate for primary cilia. Three injury models (apical resection, ischemia/reperfusion, and myocardial infarction) were used to identify the location and cell type of ciliated cells with the use of antibodies specific for cilia (acetylated tubulin, γ-tubulin, polycystin [PC] 1, PC2, and KIF3A), fibroblasts (vimentin, α-smooth muscle actin, and fibroblast-specific protein-1), and cardiomyocytes (α-actinin and troponin I). A similar approach was used to assess for primary cilia in infarcted human myocardial tissue. We studied mice silenced exclusively in myofibroblasts for PC1 and evaluated the role of PC1 in fibrogenesis in adult rat fibroblasts and myofibroblasts.

Results:

We identified primary cilia in mouse, rat, and human heart, specifically and exclusively in cardiac fibroblasts. Ciliated fibroblasts are enriched in areas of myocardial injury. Transforming growth factor β-1 signaling and SMAD3 activation were impaired in fibroblasts depleted of the primary cilium. Extracellular matrix protein levels and contractile function were also impaired. In vivo, depletion of PC1 in activated fibroblasts after myocardial infarction impaired the remodeling response.

Conclusions:

Fibroblasts in the neonatal and adult heart harbor a primary cilium. This organelle and its requisite signaling protein, PC1, are required for critical elements of fibrogenesis, including transforming growth factor β-1–SMAD3 activation, production of extracellular matrix proteins, and cell contractility. Together, these findings point to a pivotal role of this organelle, and PC1, in disease-related pathological cardiac remodeling and suggest that some of the cardiovascular manifestations of autosomal dominant polycystic kidney disease derive directly from myocardium-autonomous abnormalities.
Native Coronary Collateral Microcirculation Reserve in Rat Hearts
Authors: Liu Xiucheng , Dong Hongyan , Huang Bing , Miao Haoran , Xu Zhiwei , Yuan Yanliang , Qiu Fan , Chen Jiali , Zhang Hao , Liu Zhiwei , Quan Xiaoyu , Zhu Lidong , Zhang Zhongming
Published: March 2019

Background

We occasionally noticed that native collateral blood flow showed a recessive trend in the early stages of acute myocardial infarction in rats, which greatly interferes with the accurate assessment of native collateral circulation levels. Here, we sought to recognize the coronary collateral circulation system in depth, especially the microcirculation part, on this basis.

Methods and Results

In this study, we detected native collateral flow with positron emission tomography perfusion imaging in rats and found that the native flow is relatively abundant when it is initially recruited. However, this flow is extremely unstable in the early stage of acute myocardial infarction and quickly fails. We used tracers to mark the collateral in an ischemic area and a massive preformed collateral network was labeled. The ultrastructures of these collateral microvessels are flawed, which contributes to extensive leakage and consequent interstitial edema in the ischemic region.

Conclusions

An unrecognized short‐lived native coronary collateral microcirculation reserve is widely distributed in rat hearts. Recession of collateral blood flow transported by coronary collateral microcirculation reserve contributes to instability of native collateral blood flow in the early stage of acute myocardial infarction. The immature structure determines that these microvessels are short‐lived and provide conditions for the development of early interstitial edema in acute myocardial infarction.
Influence of 2‐Methoxyestradiol and Sex on Hypoxia‐Induced Pulmonary Hypertension and Hypoxia‐Inducible Factor‐1‐α
Authors: Docherty Craig K. , Nilsen Margaret , MacLean Margaret R.
Published: March 2019

Background

Women are at greater risk of developing pulmonary arterial hypertension, with estrogen and its downstream metabolites playing a potential role in the pathogenesis of the disease.
Hypoxia‐inducible factor‐1‐α (HIF
1α) is a pro‐proliferative mediator and may be involved in the development of human
pulmonary arterial hypertension
. The estrogen metabolite 2‐methoxyestradiol (2
ME
2) has antiproliferative properties and is also an inhibitor of
HIF
1α. Here, we examine sex differences in 
HIF
1α signaling in the rat and human pulmonary circulation and determine if 2
ME
2 can inhibit
HIF
1α in vivo and in vitro.

Methods and Results

HIF
1α signaling was assessed in male and female distal human pulmonary artery smooth muscle cells (
hPASMC
s), and the effects of 2
ME
2 were also studied in female
hPASMC
s. The in vivo effects of 2
ME
2 in the chronic hypoxic rat (male and female) model of pulmonary hypertension were also determined. Basal
HIF
1α protein expression was higher in female
hPASMC
s compared with male. Both factor‐inhibiting
HIF
and
prolyl hydroxylase‐2
(hydroxylates
HIF
leading to proteosomal degradation) protein levels were significantly lower in female
hPASMC
s when compared with males. In vivo, 2
ME
2 ablated hypoxia‐induced pulmonary hypertension in male and female rats while decreasing protein expression of
HIF
1α. 2
ME
2 reduced proliferation in
hPASMC
s and reduced basal protein expression of
HIF
1α. Furthermore, 2
ME
2 caused apoptosis and significant disruption to the microtubule network.

Conclusions

Higher basal
HIF
1α in female
hPASMC
s may increase susceptibility to developing
pulmonary arterial hypertension
. These data also demonstrate that the antiproliferative and therapeutic effects of 2
ME
2 in pulmonary hypertension may involve inhibition of
HIF
1α and/or microtubular disruption in
PASMC
s.
Intergenerational Mobility in Slums: Evidence from a Field Survey in Jakarta
Authors: Wong Maisy
Published: March 2019

Slums are central to the global debate on inequality, serving as entry points for people moving to cities in search of economic opportunity. Yet we know little about the extent of intergenerational mobility in slums due to a lack of data tracking families across generations (including family members who no longer live together), as well as a lack of data covering slums. This paper addresses these empirical challenges using a field survey of four slums in Jakarta, tracking educational mobility spanning three generations: grandparents, parents, and children. Among grandparents who have less than primary education, only 24% of their children achieve junior secondary schooling or more. By contrast, among parents with less than primary education, 69% of their children attain junior secondary schooling or more. Overall, the patterns suggest improvements in educational mobility across generations. Moreover, there is suggestive evidence that groups with high educational mobility also exhibit high occupational mobility.
Labor Market Returns to Education and English Language Skills in the People's Republic of China: An Update
Authors: Asadullah M Niaz , Xiao Saizi
Published: March 2019

We reexamine the economic returns to education in the People's Republic of China (PRC) using data from the Chinese General Social Survey 2010. We find that the conventional ordinary least squares estimate of wage returns to schooling is 7.8%, while the instrumental variable estimate is 20.9%. The gains from schooling rise sharply with higher levels of education. The estimated returns are 12.2% in urban provinces and 10.7% in coastal provinces, higher than in rural and inland areas. In addition, the wage premium for workers with good English skills (speaking and listening) is 30%. These results are robust to controls for height, body mass index, and English language skills, and to corrections for sample selection bias. Our findings, together with a critical review of existing studies, confirm the growing significance of human capital as a determinant of labor market performance in postreform PRC.
Kuznets Revisited: What Do We Know about the Relationship between Structural Transformation and Inequality?
Authors: Baymul Çinar , Sen Kunal
Published: March 2019

This paper revisits the Kuznets postulate that structural transformation will be associated with increasing inequality using comparable time series data for 32 developing and recently developed economies for the post-1950 period. We find that structural transformation in the majority of our economies has resulted in the movement of workers from agriculture to services, and not to manufacturing. Economies show different paths of structural transformation that cut across geographical regions, being either structurally underdeveloped, structurally developing, or structurally developed. We see clear differences in the structural transformation–inequality relationship depending on the stage of structural transformation that a particular economy is in, as well as across regions. We do not see a Kuznets-type relationship between manufacturing employment share and inequality when we take into account the different paths of industrialization that economies in our dataset have followed. On the other hand, inequality unambiguously increases with structural transformation if the movement of workers from agriculture is to services.
Short-Term Climatic Catastrophes and the Collapse of the Liao Dynasty (907–1125): Textual Evidence
Authors: Li Yali , Shelach-Lavi Gideon , Ellenblum Ronnie
Published: March 2019

Short-term disasters such as clusters of droughts or cold spells, lasting for just a decade or two, can induce food shortages, famines, and violence and create waves of refugees. Climatically enforced migrations can affect complex societies and, in extreme cases, even topple established bureaucracies. But the measurement of indirect signals (proxies), which is limited by the multidecadal range of radiometric dating or by the poor distribution of the better-dated signals (such as series of tree-rings, lacustrine varves, ice-cores, etc.), is often insufficient to determine the extent to which such natural disasters were the causes of particular human events in history. The introduction of historical evidence, however, can change the resolution of such indirect reconstructions and enable a more balanced and comprehensive assessment. Such an approach indicates that intense cold and other short-term climatic changes were largely responsible for the collapse of the Liao dynasty in Mongolia and northern China.
Rethinking Power Politics in an Interdependent World, 1871–1914
Authors: Mulligan William , Levy Jack S.
Published: March 2019

Interdependence altered power relations between the European great powers between 1871 and 1914 in ways that both sustained the conditions for peace and, after 1911, made a European war more likely. Interdependence accelerated the development of international financial and commercial networks. Transnational social and cultural exchanges raised the costs of a general war, offered multiple channels for states and societies to exercise influence over each other, and altered power relations. The great powers pursued their interests through not only military force but also trade deals, financial loans, expert missions (teams sent to smaller states ostensibly to aid in modernization), and cultural diplomacy. They competed for influence in smaller states. Many of the crises that pockmarked this era derived from their contested interests in such strategically vital areas in Europe as the Balkans, the Ottoman Empire, and the Low Countries, as well as elsewhere in the world. States that lost out in this transformation, notably Austria-Hungary and Russia, saw the militarization of their foreign policies as a way to compensate for weaknesses in other forms of power.
Attentive Convolution: Equipping CNNs with RNN-style Attention Mechanisms
Authors: Yin Wenpeng , Schütze Hinrich
Published: March 2019

In NLP, convolutional neural networks (CNNs) have benefited less than recurrent neural networks (RNNs) from attention mechanisms. We hypothesize that this is because the attention in CNNs has been mainly implemented as attentive pooling (i.e., it is applied to pooling) rather than as attentive convolution (i.e., it is integrated into convolution). Convolution is the differentiator of CNNs in that it can powerfully model the higher-level representation of a word by taking into account its local fixed-size context in the input text t x. In this work, we propose an attentive convolution network, ATTCONV. It extends the context scope of the convolution operation, deriving higher-level features for a word not only from local context, but also from information extracted from nonlocal context by the attention mechanism commonly used in RNNs. This nonlocal context can come (i) from parts of the input text t x that are distant or (ii) from extra (i.e., external) contexts t y. Experiments on sentence modeling with zero-context (sentiment analysis), single-context (textual entailment) and multiple-context (claim verification) demonstrate the effectiveness of ATTCONV in sentence representation learning with the incorporation of context. In particular, attentive convolution outperforms attentive pooling and is a strong competitor to popular attentive RNNs. 1
Can Lagrangian Tracking Simulate Tracer Spreading in a High-Resolution Ocean General Circulation Model?
Authors: Wagner Patrick , Rühs Siren , Schwarzkopf Franziska U. , Koszalka Inga Monika , Biastoch Arne
Published: March 2019

To model tracer spreading in the ocean, Lagrangian simulations in an offline framework are a practical and efficient alternative to solving the advective–diffusive tracer equations online. Differences in both approaches raise the question of whether both methods are comparable. Lagrangian simulations usually use model output averaged in time, and trajectories are not subject to parameterized subgrid diffusion, which is included in the advection–diffusion equations of ocean models. Previous studies focused on diffusivity estimates in idealized models but could show that both methods yield similar results as long as the deformations-scale dynamics are resolved and a sufficient amount of Lagrangian particles is used. This study compares spreading of an Eulerian tracer simulated online and a cloud of Lagrangian particles simulated offline with velocities from the same ocean model. We use a global, eddy-resolving ocean model featuring 1/20° horizontal resolution in the Agulhas region around South Africa. Tracer and particles were released at one time step in the Cape Basin and below the mixed layer and integrated for 3 years. Large-scale diagnostics, like mean pathways of floats and tracer, are almost identical and 1D horizontal distributions show no significant differences. Differences in vertical distributions, seen in a reduced vertical spreading and downward displacement of particles, are due to the combined effect of unresolved subdaily variability of the vertical velocities and the spatial variation of vertical diffusivity. This, in turn, has a small impact on the horizontal spreading behavior. The estimates of eddy diffusivity from particles and tracer yield comparable results of about 4000 m2 s−1 in the Cape Basin.
Nonlinear buckling analysis of damaged laminated composite plates
Authors: Onkar Amit K
Published: March 2019

An updated Lagrangian-based nonlinear finite element method is developed to study the buckling behavior of damaged laminated composite plates under uniaxial compression. In this study, material imperfections are treated as existing static damage and a continuum damage mechanics-based approach is used to model such imperfections. The laminated plate is modeled as a set of elementary layers bonded together by matrix-rich elastic interface. This allows to model different modes of damage present at both elementary ply level and interply interface separately. A layerwise plate model is used to model both elementary ply and interface layers of the laminate. The effect of different forms of existing static damage on the limit point loads and the corresponding displacements of laminated plates are studied. It is observed that for the chosen modes and size of the damaged regions, the limit point load does not change much as compared to the undamaged plate. However, the deformed shapes show significant changes and some very interesting phenomena like local wrinkling behaviour of the damaged region is observed. The effect of ply orientation along with different modes of damage on the limit points and the corresponding deformed shapes of laminated plates are also discussed.
With Power Comes Responsibility: How Powerful Marketing Departments Can Help Prevent Myopic Management
Authors: Srinivasan Raji , Ramani Nandini
Published: March 2019

Firms sometimes engage in myopic management (e.g., cutting marketing spending, providing lenient credit to customers to improve short-term results). Although marketing is at the center of such myopic management, there are few insights on whether a marketing department could prevent it. To address this gap, the authors examine the role of powerful marketing departments in preventing myopic marketing spending and revenue management. They hypothesize that there are internal and external enablers of marketing department power (i.e., a chief executive officer with marketing experience, the firm’s power over its customers, analyst coverage, and institutional stock ownership) that help a powerful marketing department prevent myopic management. They test the hypotheses using a panel of 781 publicly listed U.S. firms between 2000 and 2015. As hypothesized, when the firm has (1) a chief executive officer with a marketing background and (2) power over its customers, increasing marketing department power decreases the likelihood of both myopic marketing spending and myopic revenue management; increasing marketing department power and analyst coverage decreases the likelihood of myopic marketing spending. The findings highlight powerful marketing leadership as a hitherto overlooked way to prevent myopic management and improve firm performance.
“Un orgullo de Cuba en los cielos del mundo”. Cubana de aviación from Miami to Bagdad (1946–79)
Authors: Morales Etienne
Published: March 2019

This article focuses on the transformation of the carrier Cubana de aviación before and after the 1959 Cuban revolution. By observing Cubana's management, labour force, equipment, international passenger and freight traffic, this article aims to outline an international history of this Latin American flag carrier. The touristic air relationships between the American continent and Spain that could be observed in the 1950s were substituted – in the 1960s and 1970s – by a web of political “líneas de la amistad” [Friendship Flights] with Prague, Santiago de Chile, East Berlin, Lima, Luanda, Managua, Tripoli and Bagdad. This three-decade period allows us to interrogate breaks and continuities in the Cuban airline travel sector and to challenge the traditional interpretations of Cuban history. This work is based on diplomatic and corporative archives from Cuba, United States, Canada, Mexico, Spain and France and the aeronautical international press.
Association of high mobility group box 1 protein with coronary artery disease
Authors: Benlier Necla , Erdoğan Mustafa Bilge , Keçioğlu Serdar , Orhan Nuri , Çiçek Hülya
Published: March 2019

Background

Recently, the role of inflammation in coronary artery disease and the association of inflammatory biomarkers with adverse outcomes have been investigated in many studies. We investigated the relationship between high serum mobility group box 1 protein levels and established risk factors for coronary artery disease.

Methods

Fifty-five patients who presented to our Cardiovascular Surgery Clinic and subsequently underwent coronary artery bypass surgery for coronary artery disease and 50 healthy subjects presenting to the cardiology outpatient clinic without any cardiovascular problem were included in the study. The mean age was 61.47 ± 9.38 years for patients and 58.20 ± 10.15 years for controls.

Results

There was no statistically significant difference between groups with respect to age or sex. Family history of coronary artery disease, aspirin use, hypertension, and type 2 diabetes were significantly more prevalent in the patient group versus the control group. A significant difference was found between patients and healthy controls with respect to high mobility group box 1 protein levels ( p = 0.001).

Conclusions

Serum high mobility group box 1 protein was significantly increased in patients with coronary artery disease in comparison to healthy subjects. No associations were found between high mobility group box 1 protein level and certain risk factors for coronary artery disease.
Perfusion strategy and mid-term results of 58 consecutive pulmonary endarterectomy
Authors: Yan Shujie , Lou Song , Zhu Jiade , Liu Sheng , Zhao Yu , Song Yunhu , Wang Hui , Ji Bingyang
Published: March 2019

Objective:

The aim of this retrospective study was to review and report short-term and mid-term outcomes of pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension at our institute in the recent 2 years and to describe perfusion strategy.

Methods:

A total of 58 consecutive patients with chronic thromboembolic pulmonary hypertension underwent pulmonary endarterectomy under deep hypothermia circulatory arrest with an established perfusion practice between November 2015 and December 2017. Peri-operative data and patients’ outcome were retrospectively analyzed.

Results:

Mean pulmonary artery pressure was decreased (49 (40-56) mmHg vs 27 (20-31) mmHg, p < 0.001), and pulmonary vascular resistance (724 (538-1108) vs 206 (141-284) dyn second cm−5, p < 0.001) improved significantly after surgery. In-hospital mortality was 1.7% and postoperative complication rate was 27.6%. Antipsychotic medication of olanzapine was prescribed for 36 patients (62.1%), which was independently related to total deep hypothermic circulatory arrest time, postoperative blood potassium concentration, and hematocrit. The majority of patients recovered uneventfully with good mid-term cardiac function (New York Heart Association I-II: 98.1%) and neurological outcome (Glasgow Outcome Scale—Extended Upper Good Recovery: 74.1% and Lower Good Recovery: 20.3%). Mid-term neurological outcome was associated with post–pulmonary endarterectomy antipsychotic medication.

Conclusion:

Short-term and mid-term outcome after pulmonary endarterectomy was comparable to high-volume centers. Incidence of post–pulmonary endarterectomy delirium was relatively high and associated with mid-term neurological outcome. Total deep hypothermic circulatory arrest time, postoperative blood potassium concentration, and hematocrit were independent risk factors of postoperative olanzapine medication. More efforts and further research are required to optimize the neuroprotection of perfusion practice.
A Systematic Review of the Literature Demonstrates Some Errors in the Use of Decision Curve Analysis but Generally Correct Interpretation of Findings
Authors: Capogrosso Paolo , Vickers Andrew J.
Published: March 2019

Background. Decision curve analysis (DCA) is a widely used methodology in clinical research studies. Purpose. We performed a literature review to identify common errors in the application of DCA and provide practical suggestions for appropriate use of DCA. Data Sources. We first conducted an informal literature review and identified 6 errors found in some DCAs. We then used Google Scholar to conduct a systematic review of studies applying DCA to evaluate a predictive model, marker, or test. Data Extraction. We used a standard data collection form to collect data for each reviewed article. Data Synthesis. Each article was assessed according to the 6 predefined criteria for a proper analysis, reporting, and interpretation of DCA. Overall, 50 articles were included in the review: 54% did not select an appropriate range of probability thresholds for the x-axis of the DCA, with a similar proportion (50%) failing to present smoothed curves. Among studies with internal validation of a predictive model and correction for overfit, 61% did not clearly report whether the DCA had also been corrected. However, almost all studies correctly interpreted the DCA, used a correct outcome (92% for both), and clearly reported the clinical decision at issue (81%). Limitations. A comprehensive assessment of all DCAs was not performed. However, such a strategy would not influence the main findings. Conclusions. Despite some common errors in the application of DCA, our finding that almost all studies correctly interpreted the DCA results demonstrates that it is a clear and intuitive method to assess clinical utility.