bluuebunny/crossref_metadata_2025 huggingface dataset:
Uterine Tumor Resembling Ovarian Sex-Cord Tumors Initially Diagnosed as a Prolapsed Fibroid
Authors: Rozário Garcia Fernando Augusto , Gaigher Vanessa Pereira , Neves Ferreira Rodrigo , Chambô Filho Antônio
Published: July 2018

Background. First described in 1945 by Morehead and Bowman, uterine tumors resembling ovarian sex-cord tumors (UTROSCT) are rare tumors of the uterine body that tend to occur in menopausal women presenting with abnormal vaginal bleeding, abdominal pain, and increased uterine volume. UTROSCT are usually diagnosed from incidental histological findings following hysterectomy performed due to a suspected endometrial polyp or uterine fibroids. Objective. To report on a 46-year-old patient with abnormal vaginal bleeding. At physical examination, a pediculated nodular lesion was found protruding from the external cervical os. Histopathology of the resected lesion led to a diagnosis of UTROSCT. Total abdominal hysterectomy with bilateral adnexectomy was then performed. The patient is currently undergoing regular outpatient follow-up, with no evidence of disease after one year. Methods. Data were retrieved from the patient’s records, and macroscopic and microscopic images of the tumor were obtained. Discussion. Reports of metastasis or recurrence are rare. UTROSCT are considered of uncertain malignant potential and no particular form of treatment is formally recommended, with hysterectomy currently being the treatment of choice. This patient will be followed up for five years during which clinical examination and tomography of the chest, abdomen, and pelvis will be performed annually.
Clozapine-Induced Myocarditis or Acute Coronary Syndrome? Optical Coherence Tomography to the Rescue
Authors: Dina Ayodeji , Barlis Peter , van Gaal William
Published: July 2018

Chest pain and troponin elevation may be due to an acute coronary syndrome, myocarditis, acute cardiomyopathy, or other less common conditions. Management differs depending on the aetiology, and the pathophysiologic diagnosis has direct implications on treatment and patient outcomes. History and clinical examination is supplemented by selected investigations including the electrocardiogram, chest X-ray, echocardiography, coronary angiography, and even myocardial perfusion scintigraphy or cardiac magnetic resonance imaging. Intravascular imaging can provide important insights into the underlying mechanism of acute coronary syndromes, especially when angiography is ambiguous.
Numerical Investigation on the Effects of Structural Parameters of Labyrinth Cavity on Sealing Performance
Authors: Feng Jianmei , Wang Lingzi , Yang Hang , Peng Xueyuan
Published: July 2018

This paper presents a study on the leakage characteristics of a labyrinth piston compressor. A computational fluid dynamics model was applied to predict the effects of different structural parameters of the labyrinth seal on the sealing performance. The velocity field through the sealing clearance and labyrinth cavity was demonstrated and analyzed. An experimental rig was built to validate the simulation model, and the results of the simulation and experimental data showed a good agreement. The effects of the cavity width, cavity depth, tooth thickness, and clearance of the seal on the leakage characteristics were discussed in detail. The results showed that, except for the significant influence of the labyrinth clearance, d/δ (the ratio of cavity depth to labyrinth clearance) should be bigger than 2.7 to achieve the minimum leakage flow, and the effect of the varied cavity width can be ignored. Moreover, when the piston length and cavity width remain constant, the thinner the tooth thickness, the greater the number of labyrinth cavities that can be arranged, and the higher the sealing performance achieved.
Controlled Depolymerization of Cellulose Fibres Isolated from Lignocellulosic Biomass Wastes
Authors: Pang Suh Cem , Voon Lee Ken , Chin Suk Fun
Published: July 2018

Various types of lignocellulosic biomass wastes (LBW) had been successfully converted into cello-oligomers with different chain lengths via a controlled depolymerization process. Cellulose fibres isolated from LBW samples were dissolved with room temperature ionic liquid (RTIL) in the presence of an acid catalyst, Amberlyst 15 DRY. The effects of reaction time on the degree of polymerization and yields of water-insoluble cello-oligomers formed were studied. Besides, the yields of water-soluble cello-oligomers such as glucose and xylose were also determined. The depolymerization of cellulose fibres isolated from LBW was observed to follow both second-order and pseudo-second order kinetics under specific conditions. As such, cello-oligomers of controllable chain lengths could be obtained by adjusting the duration of depolymerization process under optimized conditions.
Robust Sliding Mode Predictive Control of Uncertain Networked Control System with Random Time Delay
Authors: Zhang Yu , Xie Shousheng , Zhang Ledi , Ren Litong
Published: July 2018

This paper proposes a sliding mode predictive controller with a new robust global sliding surface for a certain networked control system with random time delay, mismatched parametric uncertainty, and external disturbances. First, the model of the networked control system is established, based on which linear transformation is made to get a new form of the system which does not have time delay term in expression. Then a global sliding surface is proposed followed by the sufficient condition given in the form of linear matrix inequality (LMI) to guarantee system stability and robustness. Subsequently, a sliding mode predictive controller is proposed with modified reaching law as its reference trajectory and the rolling optimization method is combined to provide optimal control input for each step so that chattering can be minimized. Finally, simulations have been made and the results indicate the advantages of the proposed controller in the aspect of convergence speed, chattering suppression, and robustness to uncertainties.
Two Years of Gynecomastia Caused by Leydig Cell Tumor
Authors: Zeuschner Philip , Veith Christian , Linxweiler Johannes , Stöckle Michael , Heinzelbecker Julia
Published: July 2018

Gynecomastia is a common incidental finding in males that can be caused by various benign or malignant diseases. In rare cases, it results from Leydig cell tumors, a rare entity accounting for 3% of all testicular neoplasms. Some of them are hormonally active but seldom cause symptomatic endocrine disturbance. Here we report on a 32-year-old male presenting with gynecomastia which he had already been suffering from for two years. Although he had been seen by three other specialists, including a urologist, none of them found the small mass in the upper pole of his right testis. We decided to perform testis-sparing surgery which confirmed the diagnosis of a hormonally active Leydig cell tumor. During follow-up, hormonal status normalized, and gynecomastia began to resolve.
Subinhibitory Concentrations of Prim‐O‐Glucosylcimifugin Decrease the Expression of Alpha‐Hemolysin in Staphylococcus aureus (USA300)
Authors: Ping Ouyang , Ruixue Yang , Jiaqiang Deng , Kaiyu Wang , Jing Fang , Yi Geng , Xiaoli Huang , Defang Chen , Weimin Lai , Li Tang , Lizi Yin
Published: July 2018

Staphylococcus aureus (S. aureus), an important opportunistic pathogen in human and animal, causes a series of diseases in the impairing of immunity of host and even then death. Alpha‐hemolysin (Hla), a primary virulence factor, plays a major role in the pathogenic progress of S. aureus, especially in pneumonia. Prim‐O‐glucosylcimifugin (POG), a nature chromone compound, is an active ingredient in many Chinese Medicines. In this study, POG investigated the inhibitory effect of the secretion of Hla in S. aureus strain USA300 at the subinhibitory concentrations. The hemolysis assays and western blotting assays showed that POG can decrease the production of Hla in the USA300 growth cell cultures in a dose‐dependent manner. The results of RT‐PCR revealed that reduction of Hla was related to inhibit the transcription of hla and RNAIII. In the cells experiment, POG was proved to protect A549 cells from Hla‐medicated injury. In conclusion, POG was shown the capacity of decreased the production of S. aureus Hla. POG can be developed as a candidate agent to treat S. aureus infections against Hla.
Effect of Multiwalled Carbon Nanotubes and Electroless Copper Plating on the Tensile Behavior of Carbon Fiber Reinforced Polymers
Authors: Truong Gia Toai , Kim Jiho , Choi Kyoung-Kyu
Published: July 2018

Multiwalled carbon nanotubes (MWCNTs) and nanoscaled electroless copper plating were introduced to enhance the mechanical properties of carbon fiber reinforced polymer (CFRP) composites in this study. The influence of multiwalled carbon nanotubes (MWCNTs) with weight fractions of 0.5–1.5% of epoxy resin on the mechanical properties of CFRP composites was investigated. The MWCNTs and epoxy resin was first mixed, prior to impregnating the carbon fiber fabrics. Electroless copper plating, a deposit method using simultaneous reactions in an aqueous (copper) solution without external electric power, was applied on the carbon fiber surface, and the effect was also investigated. The CFRP test specimens were fabricated by hand lay‐up method, using one or three carbon fiber fabrics. The mechanical properties of the CFRP test specimens were derived by tensile tests according to KS M ISO 527‐4. According to the morphology taken by SEM, the carbon fiber surface was significantly rough with copper ions. Because of this, the strength and ultimate strain of coated specimens increased up to 26.3 and 18.6% compared to noncoated specimens, respectively. In addition, as the MWCNTs amount increased, the ultimate strain of the composites also increased. In the case of CFRP test specimens using noncoated carbon fiber fabrics, the addition of 1.5% wt. MWCNTs increased the peak strength and ultimate strain of CFRP specimens up to 80.5 and 48.8%, respectively. Finally, the tensile stress‐strain relationship of CFRP specimens was idealized as bilinear or trilinear response curves.
Successful Management of Pheochromocytoma Detected in Pregnancy by Interval Adrenalectomy in a VHL Patient
Authors: Kaluarachchi V. T. S. , Bulugahapitiya Uditha , Arambewela Maulee , Gunathilake Sonali
Published: July 2018

A 34-year-old mother with diabetes mellitus for 6 years presented in the late second trimester of her third pregnancy with new onset hypertension and characteristic hyperadrenergic spells. Clinical examination was unremarkable except a blood pressure of 170/110 mmhg. She had an elevated 24 hour urinary normetanephrine level with ultrasonic evidence of a hyperechoic hypervascular well-defined right supra renal mass of 6 x 5 cm in size which was very suggestive of a pheochromocytoma. Her management decisions were made by a multidisciplinary team which decided to deliver the baby by lower segment cesarean section (LSCS) as the pregnancy was advanced and to proceed with interval adrenalectomy after contrast enhanced computer tomography (CECT) of the abdomen with adrenal protocol. As a result a healthy baby was delivered by an uncomplicated elective LSCS at 36 weeks of POA. CECT abdomen with adrenal protocol confirmed a right-sided pheochromocytoma without any evidence of metastasis. Uncomplicated laparoscopic right adrenalectomy led to a clinical and biochemical recovery of the patient while histology confirmed the pheochromocytoma without any evidence of invasion. Subsequent follow up revealed cerebellar hemangioblastomas and retinal angioma in the right eye which led to a clinical diagnosis of Von Hippel Lindau disease (VHL). Even though clinical criteria for Von Hippel Lindau disease were fulfilled, her VHL genetic test was negative. At present she and her family are under surveillance of the endocrine team.
A Security Sandbox Approach of Android Based on Hook Mechanism
Authors: Jiang Xin , Liu Mingzhe , Yang Kun , Liu Yanhua , Wang Ruili
Published: July 2018

As the most widely applied mobile operating system for smartphones, Android is challenged by fast growing security problems, which are caused by malicious applications. Behaviors of malicious applications have become more and more inconspicuous, which largely increase the difficulties of security detection. This paper provides a new security sandbox approach of Android based on hook mechanism, to further enrich Android malware detection technologies. This new sandbox monitors the behaviors of target application by using a process hook-based dynamic tracking method during its running period. Compared to existing techniques, (1) this approach can create a virtual space where apk can be installed, run, and uninstalled, and it is isolated from the outside and (2) a risk assessment approach based on behavior analysis is given so that users can obtain an explicit risk prognosis for an application to improve their safety. Tests on malware and normal application samples verify this new security sandbox.
Oncogenic BRAFV600E Governs Regulatory T-cell Recruitment during Melanoma Tumorigenesis
Authors: Shabaneh Tamer B. , Molodtsov Aleksey K. , Steinberg Shannon M. , Zhang Peisheng , Torres Gretel M. , Mohamed Gadisti A. , Boni Andrea , Curiel Tyler J. , Angeles Christina V. , Turk Mary Jo
Published: July 2018

Regulatory T cells (Treg) are critical mediators of immunosuppression in established tumors, although little is known about their role in restraining immunosurveillance during tumorigenesis. Here, we employ an inducible autochthonous model of melanoma to investigate the earliest Treg and CD8 effector T-cell responses during oncogene-driven tumorigenesis. Induction of oncogenic BRAFV600E and loss of Pten in melanocytes led to localized accumulation of FoxP3+ Tregs, but not CD8 T cells, within 1 week of detectable increases in melanocyte differentiation antigen expression. Melanoma tumorigenesis elicited early expansion of shared tumor/self-antigen–specific, thymically derived Tregs in draining lymph nodes, and induced their subsequent recruitment to sites of tumorigenesis in the skin. Lymph node egress of tumor-activated Tregs was required for their C-C chemokine receptor 4 (Ccr4)–dependent homing to nascent tumor sites. Notably, BRAFV600E signaling controlled expression of Ccr4-cognate chemokines and governed recruitment of Tregs to tumor-induced skin sites. BRAFV600E expression alone in melanocytes resulted in nevus formation and associated Treg recruitment, indicating that BRAFV600E signaling is sufficient to recruit Tregs. Treg depletion liberated immunosurveillance, evidenced by CD8 T-cell responses against the tumor/self-antigen gp100, which was concurrent with the formation of microscopic neoplasia. These studies establish a novel role for BRAFV600E as a tumor cell–intrinsic mediator of immune evasion and underscore the critical early role of Treg-mediated suppression during autochthonous tumorigenesis.

Significance: This work provides new insights into the mechanisms by which oncogenic pathways impact immune regulation in the nascent tumor microenvironment. Cancer Res; 78(17); 5038–49. ©2018 AACR.
Oligosaccharyltransferase Inhibition Overcomes Therapeutic Resistance to EGFR Tyrosine Kinase Inhibitors
Authors: Lopez Sambrooks Cecilia , Baro Marta , Quijano Amanda , Narayan Azeet , Cui Wei , Greninger Patricia , Egan Regina , Patel Abhijit , Benes Cyril H. , Saltzman W. Mark , Contessa Joseph N.
Published: July 2018

Asparagine (N)-linked glycosylation is a posttranslational modification essential for the function of complex transmembrane proteins. However, targeting glycosylation for cancer therapy has not been feasible due to generalized effects on all glycoproteins. Here, we perform sensitivity screening of 94 lung cancer cell lines using NGI-1, a small-molecule inhibitor of the oligosaccharyltransferase (OST) that partially disrupts N-linked glycosylation, and demonstrate a selective loss of tumor cell viability. This screen revealed NGI-1 sensitivity in just 11 of 94 (12%) cell lines, with a significant correlation between OST and EGFR inhibitors. In EGFR-mutant non-small cell lung cancer with EGFR tyrosine kinase inhibitor (TKI) resistance (PC9-GR, HCC827-GR, and H1975-OR), OST inhibition maintained its ability to induce cell-cycle arrest and a proliferative block. Addition of NGI-1 to EGFR TKI treatment was synthetic lethal in cells resistant to gefitinib, erlotinib, or osimertinib. OST inhibition invariably disrupted EGFR N-linked glycosylation and reduced activation of receptors either with or without the T790M TKI resistance mutation. OST inhibition also dissociated EGFR signaling from other coexpressed receptors like MET via altered receptor compartmentalization. Translation of this approach to preclinical models was accomplished through synthesis and delivery of NGI-1 nanoparticles, confirmation of in vivo activity through molecular imaging, and demonstration of significant tumor growth delay in TKI-resistant HCC827 and H1975 xenografts. This therapeutic strategy breaks from kinase-targeted approaches and validates N-linked glycosylation as an effective target in tumors driven by glycoprotein signaling.

Significance: EGFR-mutant NSCLC is incurable despite the marked sensitivity of these tumors to EGFR TKIs. These findings identify N-linked glycosylation, a posttranslational modification common to EGFR and other oncogenic signaling proteins, as an effective therapeutic target that enhances tumor responses for EGFR-mutant NSCLC. Cancer Res; 78(17); 5094–106. ©2018 AACR.
Matrix Stiffening and EGFR Cooperate to Promote the Collective Invasion of Cancer Cells
Authors: Grasset Eloise M. , Bertero Thomas , Bozec Alexandre , Friard Jonas , Bourget Isabelle , Pisano Sabrina , Lecacheur Margaux , Maiel Majdi , Bailleux Caroline , Emelyanov Alexander , Ilie Marius , Hofman Paul , Meneguzzi Guerrino , Duranton Christophe , Bulavin Dmitry V. , Gaggioli Cedric
Published: July 2018

In squamous cell carcinoma (SCC), tissue invasion by collectively invading cells requires physical forces applied by tumor cells on their surrounding extracellular matrix (ECM). Cancer-related ECM is composed of thick collagen bundles organized by carcinoma-associated fibroblasts (CAF) within the tumor stroma. Here, we show that SCC cell collective invasion is driven by the matrix-dependent mechano-sensitization of EGF signaling in cancer cells. Calcium (Ca2+) was a potent intracellular second messenger that drove actomyosin contractility. Tumor-derived matrix stiffness and EGFR signaling triggered increased intracellular Ca2+ through CaV1.1 expression in SCC cells. Blocking L-type calcium channel expression or activity using Ca2+ channel blockers verapamil and diltiazem reduced SCC cell collective invasion both in vitro and in vivo. These results identify verapamil and diltiazem, two drugs long used in medical care, as novel therapeutic strategies to block the tumor-promoting activity of the tumor niche.

Significance: This work demonstrates that calcium channels blockers verapamil and diltiazem inhibit mechano-sensitization of EGF-dependent cancer cell collective invasion, introducing potential clinical strategies against stromal-dependent collective invasion.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/18/5229/F1.large.jpg. Cancer Res; 78(18); 5229–42. ©2018 AACR.
Targeting CCR8 Induces Protective Antitumor Immunity and Enhances Vaccine-Induced Responses in Colon Cancer
Authors: Villarreal Daniel O. , L'Huillier Andrew , Armington Susan , Mottershead Cristina , Filippova Elena V. , Coder Brandon D. , Petit Robert G. , Princiotta Michael F.
Published: July 2018

CCR8 is a chemokine receptor expressed principally on regulatory T cells (Treg) and is known to be critical for CCR8+ Treg-mediated immunosuppression. Recent studies have demonstrated that CCR8 is uniquely upregulated in human tumor-resident Tregs of patients with breast, colon, and lung cancer when compared with normal tissue-resident Tregs. Therefore, CCR8+ tumor-resident Tregs are rational targets for cancer immunotherapy. Here, we demonstrate that mAb therapy targeting CCR8 significantly suppresses tumor growth and improves long-term survival in colorectal tumor mouse models. This antitumor activity correlated with increased tumor-specific T cells, enhanced infiltration of CD4+ and CD8+ T cells, and a significant decrease in the frequency of tumor-resident CD4+CCR8+ Tregs. Tumor-specific CD8+ T cells displayed lower expression of exhaustion markers as well as increased functionality upon restimulation. Treatment with anti-CCR8 mAb prevented de novo induction and suppressive function of Tregs without affecting CD8+ T cells. Initial studies explored a combinatorial regimen using anti-CCR8 mAb therapy and a Listeria monocytogenes–based immunotherapy. Anti-CCR8 mAb therapy synergized with L. monocytogenes–based immunotherapy to significantly delay growth of established tumors and to prolong survival. Collectively, these findings identify CCR8 as a promising new target for tumor immunotherapy and provide a strong rationale for further development of this approach, either as a monotherapy or in combination with other immunotherapies.

Significance: Inhibition of CCR8 represents a promising new cancer immunotherapy strategy that modulates tumor-resident regulatory T cells to enhance antitumor immunity and prolong patient survival. Cancer Res; 78(18); 5340–8. ©2018 AACR.
Cancer Site–Specific Disparities in New York, Including the 1945–1965 Birth Cohort's Impact on Liver Cancer Patterns
Authors: Pinheiro Paulo S. , Callahan Karen E. , Boscoe Francis P. , Balise Raymond R. , Cobb Taylor R. , Lee David J. , Kobetz Erin
Published: July 2018

Background: Analyses of cancer patterns by detailed racial/ethnic groups in the Northeastern United States are outdated.

Methods: Using 2008–2014 death data from the populous and diverse New York State, mortality rates and regression-derived ratios with corresponding 95% confidence intervals (CIs) were computed to compare Hispanic, non-Hispanic white (NHW), non-Hispanic black (NHB), Asian populations, and specific Hispanic and NHB subgroups: Puerto Rican, Dominican, South American, Central American, U.S.-born black, and Caribbean-born black. Special analyses on liver cancer mortality, given the higher prevalence of hepatitis C infection among the 1945–1965 birth cohort, were performed.

Results: A total of 244,238 cancer-related deaths were analyzed. Mortality rates were highest for U.S.-born blacks and lowest for South Americans and Asians. Minority groups had higher mortality from liver and stomach cancer than NHWs; Hispanics and NHBs also had higher mortality from cervical and prostate cancers. Excess liver cancer mortality among Puerto Rican and U.S.-born black men was observed, particularly for the 1945–1965 birth cohort, with mortality rate ratios of 4.27 (95% CI, 3.82–4.78) and 3.81 (95% CI, 3.45–4.20), respectively.

Conclusions: U.S.-born blacks and Puerto Ricans, who share a common disadvantaged socioeconomic profile, bear a disproportionate burden for many cancers, including liver cancer among baby boomers. The relatively favorable cancer profile for Caribbean-born blacks contrasts with their U.S.-born black counterparts, implying that race per se is not an inevitable determinant of higher mortality among NHBs.

Impact: Disaggregation by detailed Hispanic and black subgroups in U.S. cancer studies enlightens our understanding of the epidemiology of cancer and is fundamental for cancer prevention and control efforts. Cancer Epidemiol Biomarkers Prev; 27(8); 917–27. ©2018 AACR.
Perinatal Anemia is Associated with Neonatal and Neurodevelopmental Outcomes in Infants with Moderate to Severe Perinatal Asphyxia
Authors: Kalteren Willemien S. , ter Horst Hendrik J. , den Heijer Anne E. , de Vetten Leanne , Kooi Elisabeth M.W. , Bos Arend F.
Published: July 2018

Background: Perinatal anemia may cause perinatal asphyxia. Its pathophysiology and neurodevelopmental effects are theoretically different from other causes of perinatal asphyxia. Objective: The study aimed to determine whether perinatal anemia results in different short-term and long-term outcomes than other causes of perinatal asphyxia treated with therapeutic hypothermia. Methods: We retrospectively included infants with moderate to severe hypoxic-ischemic encephalopathy, born between May 2009 and October 2015. During follow-up, we assessed cognitive and motor development at 2–3 years of age, using the Bayley Scales of Infant and Toddler Development, third edition (BSID-III). Neurodevelopmental outcome (NDO) was classified as abnormal in case of cerebral palsy with Gross Motor Function Classification System ≥III and/or a BSID-III composite score < 85. Outcomes of infants with perinatal anemia (initial hemoglobin < 7 mmol/L) were compared to infants born with perinatal asphyxia due to other causes. Results: In total, 111 infants were included of whom 30 infants (27%) died during the neonatal period. Infants with anemia (n = 23) had a higher mortality risk, OR 3.33, 95% CI 1.27–8.72, p = 0.01. None of the surviving infants with anemia (n = 12) had an abnormal NDO, in contrast to 26/69 (38%) with neurodevelopmental impairments, particularly motor problems, in the non-anemic group, p < 0.01. Conclusions: Perinatal anemia causing moderate to severe perinatal asphyxia is associated with a higher risk for neonatal mortality. All survivors with perinatal anemia, however, showed a normal NDO in contrast to children who were born asphyxiated due to other causes. The underlying pathophysiological mechanism for the favorable NDO in the perinatal anemia group needs further elucidation.
Biomarker Discovery by Mass Spectrometry in Cerebrospinal Fluid and Plasma after Global Hypoxia-Ischemia in Newborn Piglets
Authors: Kyng Kasper Jacobsen , Edhager Anders Valdemar , Henriksen Tine Brink , Swan Christer Zøylner , Gregersen Niels , Palmfeldt Johan
Published: July 2018

Background: Biomarkers may qualify diagnosis, treatment allocation, and prognostication in neonatal encephalopathy. Biomarker development is challenged by competing etiologies, inter-individual genetic variability, and a lack of specific neonatal markers. To address these challenges, we used a standardized neonatal hypoxic-ischemic (HI) encephalopathy model with pre- and post-HI sampling of cerebrospinal fluid (CSF) and plasma. Objectives: The study aimed to identify novel candidate protein biomarkers of HI encephalopathy in a newborn piglet model in CSF and plasma. Methods: FiO2 was lowered to 4% in 6 newborn piglets, then adjusted over a 45-min period keeping the amplitude integrated-EEG < 7 µV to induce HI encephalopathy. CSF and plasma was sampled pre-HI and 2 h after HI, protein levels were then analyzed by mass spectrometry. Results: Protein levels after HI changed significantly for 18 CSF proteins and 37 plasma proteins. CSF and plasma data showed distinct information, although peptidyl-prolyl cis-trans isomerase A had elevated levels in both fluids. HI regulation involved functional groups such as the antioxidant system, cell proliferation, cell structure, and apoptosis. S100-A8, which increased the most in CSF (9.5 fold), is known to be involved in inflammatory and immune response and to be highly regulated during injury. In plasma, increased proteins included FABP1 (31.8 fold) and proteins with antioxidant (SOD1, GPX3) and lectin function (REG3A, LGALS3). Conclusions: In this exploratory study, we have identified candidate biomarkers for HI in CSF and plasma, many not previously associated with HI. Identified proteins are promising candidates for further validation in time series experiments and clinical studies.
Presentation, Evaluation, Management, and Outcomes of Acute Stroke in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis
Authors: Khatib Rasha , Arevalo Yurany A. , Berendsen Mark A. , Prabhakaran Shyam , Huffman Mark D.
Published: July 2018

Aims: We performed a systematic review to evaluate stroke presentation, evaluation, management, and outcomes among studies conducted in low- and middle-income countries (LMIC). Methods: We searched MEDLINE (Ovid), Embase (Elsevier), and the Global Health (EBSCOhost) databases between January 2005 and June 2017 for studies conducted in LMICs defined by the World Bank. We pooled prevalence estimates using an inverse-variance weighting method and stratified by the country income group. Results: The search identified 36 hospital-based studies (64,256 participants) in LMICs. Mean (SD) age ranged from 51 (14) to 72 (12) years, and 29–56% of patients were women. Hypertension was the most commonly reported risk factor (64% [95% CI 59–69]). In settings where MRI was not used, head CT scans were reported among 90% patients (95% CI 79–97). Overall, 3% (95% CI 2–4) of patients were treated with tissue plasminogen activator, and 78% (95% CI 66–88) were treated with antiplatelet therapy. Overall, the rate of in-hospital mortality was 14% (95% CI 10–19), and the rate of in-hospital pneumonia was 17% (95% CI 14–20). Conclusions: Our review revealed the low use of evidence-based practices for acute stroke care in LMIC. The true use in hospitals that do not conduct this research is probably even lower. Strategies to evaluate and improve health system performance for acute stroke care, including implantation of stroke units and making thrombolysis more available and affordable are needed in LMIC. Registration in Prospero: CRD42017069325.
Monocrotaline Suppresses RANKL-Induced Osteoclastogenesis In Vitro and Prevents LPS-Induced Bone Loss In Vivo
Authors: Wei Cheng-Ming , Su Yi-Ji , Qin Xiong , Ding Jia-Xin , Liu Qian , Song Fang-Ming , Zong Shao-Hui , Xu Jiake , Zhou Bo , Zhao Jin-Min
Published: July 2018

Background/Aims: Extensive osteoclast formation plays a critical role in bone diseases, including rheumatoid arthritis, periodontitis and the aseptic loosening of orthopedic implants. Thus, identification of agents that can suppress osteoclast formation and bone resorption is important for the treatment of these diseases. Monocrotaline (Mon), the major bioactive component of crotalaria sessiliflora has been investigated for its anti-cancer activities. However, the effect of Mon on osteoclast formation and osteolysis is not known. Methods: The bone marrow macrophages (BMMs) were cultured with M-CSF and RANKL followed by Mon treatment. Then the effects of Mon on osteoclast differentiation were evaluated by counting TRAP (+) multinucleated cells. Moreover, effects of Mon on hydroxyapatite resorption activity of mature osteoclast were studied through resorption areas measurement. The involved potential signaling pathways were analyzed by performed Western blotting and quantitative real-time PCR examination. Further, we established a mouse calvarial osteolysis model to measure the osteolysis suppressing effect of Mon in vivo. Results: In this study, we show that Mon can inhibit RANKL-induced osteoclast formation and function in a dose-dependent manner. Mon inhibits the expression of osteoclast marker genes such as tartrate-resistant acid phosphatase (TRAP) and cathepsin K. Furthermore, Mon inhibits RANKL-induced the activation of p38 and JNK. Consistent with in vitro results, Mon exhibits protective effects in an in vivo mouse model of LPS-induced calvarial osteolysis. Conclusion: Taken together our data demonstrate that Mon may be a potential prophylactic anti-osteoclastic agent for the treatment of osteolytic diseases caused by excessive osteoclast formation and function.
SIRT1 Involved in the Regulation of Alternative Splicing Affects the DNA Damage Response in Neural Stem Cells
Authors: Wang Guangming , Wang Fangce , Ren Jie , Qiu Yue , Zhang Wenjun , Gao Shane , Yang Danjing , Wang Zhigang , Liang Aibin , Gao Zhengliang , Xu Jun
Published: July 2018

Background/Aims: Alternative splicing and DNA damage exhibit cross-regulation, with not only DNA damage inducing changes in alternative splicing, but alternative splicing itself possibly modulating the DNA damage response (DDR). Sirt1, a prominent anti-aging player, plays pivotal roles in the DDR. However, few studies have examined alternative splicing with DNA damage in neural stem cells (NSCs) and, in essence, nothing is known about whether SIRT1 regulates alternative splicing. Hence, we investigated the potential involvement of Sirt1-mediated alternative splicing in the NSC DDR. Methods: Genome-wide alternative splicing profiling was performed upon DNA damage induction and SIRT1 deletion. Results: DNA damage caused genome-wide changes in alternative splicing in adult NSCs and Sirt1 deficiency dramatically altered DDR-related alternative splicing. In particular, extensive alternative splicing changes in DDR-related processes such as cell cycle control and DNA damage repair were observed; these processes were dramatically influenced by Sirt1 deficiency. Phenotypically, Sirt1 deficiency altered the proliferation and DNA repair of adult NSCs, possibly by regulating alternative splicing. Conclusion: SIRT1 helps to regulate alternative splicing, which itself affects the DDR of NSCs. Our findings provide novel insight into the mechanisms underlying the DDR in stem cells.
Identifying Prognostic Factors for Well-Differentiated Metastatic Pancreatic Neuroendocrine Tumours: A Retrospective International Multicentre Cohort Study
Authors: Jiménez-Fonseca Paula , Krug Sebastian , Tamagno Gianluca , Fierro Maya Felipe , Monléon Getino Antonio , Rodriguez Casado Clara Isabel , Costa Frederico , de Herder Wouter W. , Jann Henning
Published: July 2018

Pancreatic neuroendocrine tumours (pNETs) represent rare neoplasms of all NETs often presenting without functional activity. Many sporadic non-functioning pNET patients are already metastatic at the time of diagnosis, and the therapeutic approach to such patients is mostly palliative. In this international, multicentre, retrospective cohort study, we assessed the prognostic value of a set of anthropometric, clinical, biochemical, radiological and pathological parameters at baseline and the impact of the therapeutic strategies on the survival of patients with sporadic grade 1/2, stage IV, non-functioning pNETs. Three hundred and twelve consecutive patients diagnosed between 1993 and 2010 were included. The median overall survival (OS) was 6.6 years and survival at 5 and 10 years was 62 and 34% respectively. On univariate analysis, Eastern Cooperative Oncology Group (ECOG) status ≥2, grade 2, bilobar hepatic metastases, synchronous metastases, and high chromogranin A, alkaline-phosphatase and lactic-dehydrogenase were associated with a significant reduction of OS. Palliative/curative surgery and loco-regional hepatic interventions were significant factors improving OS. On multivariate analysis, ECOG status ≥2, synchronous metastases, Ki-67 ≥10%, and high alkaline-phosphatase correlated significantly with an increased risk of death. Both palliative/curative surgery and loco-regional hepatic interventions had a positive impact on OS. Although most parameters did not prove to be independent OS predictors at multivariate analysis, they showed a tendency towards that. Future prospective studies including larger patient populations may give greater clarity. We believe the integration of these parameters has the potential to provide a reliable prognostic score for the stratification of patients with sporadic well-differentiated metastatic non-functioning pNETs.
Medium-Chain Acylcarnitines Are Associated With Cardioembolic Stroke and Stroke Recurrence
Authors: Seo Woo-Keun , Jo Garam , Shin Min-Jeong , Oh Kyungmi
Published: July 2018

Objective—

Stroke is a heterogeneous disease with diverse causes, which affect the risk of recurrence. This study aimed to identify novel biomarkers that are clinically relevant to the diagnosis of cardioembolic stroke (CE) and the prediction of stroke recurrence using metabolomics.

Approach and Results—

We obtained blood samples and clinical data from a consecutively registered, hospital-based acute stroke registry and from healthy controls. Mass-spectrometry–based profiling was performed, and several metabolomic signatures were selected for the discrimination of CE and stroke recurrence, coupled with multivariate statistical analysis. Finally, 190 acute ischemic stroke participants (43 CE patients and 147 non-CE patients) and 30 control participants were included. We obtained 29 metabolomics signatures, and of these, 2 medium-chain acylcarnitines (decanoylcarnitine and octanoylcarnitine) were selected as independent discriminants for CE (odds ratio, 2.839; 95% CI, 1.241–6.493 for decanoylcarnitine; odds ratio, 2.839; 95% CI, 1.241–6.493 for octanoylcarnitine). Elevated medium-chain acylcarnitines were also associated with a higher risk of stroke recurrence (hazard ratio, 3.767; 95% CI, 1.276–11.117 for decanoylcarnitine; hazard ratio, 5.519; 95% CI, 1.22–18.781 for octanoylcarnitine). The levels of decanoylcarnitine and octanoylcarnitine were correlated as known surrogate markers of CE. The levels of decanoylcarnitine and octanoylcarnitine were significantly higher in stroke patients with a high-risk potential of cardioembolism than in those with low or intermediate risk.

Conclusions—

Metabolomics provided an improved understanding of CE pathogenesis and stroke recurrence. We have identified decanoylcarnitine and octanoylcarnitine as novel biomarkers for CE and stroke recurrence.
Calcification Induced by Type I Interferon in Human Aortic Valve Interstitial Cells Is Larger in Males and Blunted by a Janus Kinase Inhibitor
Authors: Parra-Izquierdo Iván , Castaños-Mollor Irene , López Javier , Gómez Cristina , San Román J. Alberto , Sánchez Crespo Mariano , García-Rodríguez Carmen
Published: July 2018

Objective—

Calcific aortic valve disease is the most prevalent valvulopathy in Western countries. An unanticipated pathogenetic clue involving IFN (interferon) was disclosed by the finding of constitutive type I IFN activity associated with aortic valve calcification in children with the atypical Singleton-Merten syndrome. On this basis, the role of type I IFN on inflammation and calcification in human aortic valve interstitial cells (AVIC) was examined.

Approach and Results—

IFN-α was weakly proinflammatory but potentiated lipopolysaccharide-mediated activation of NF (nuclear factor)-κB and the ensuing induction of proinflammatory molecules in human AVIC. Stimulation with IFN-α and in combination with lipopolysaccharide promoted osteoblast-like differentiation characterized by increased osteoblastic gene expression, BMP (bone morphogenetic protein)-2 secretion, and ectopic phosphatase activity. Sex differences were observed. Likewise, IFN-α treatment of human AVICs in osteogenic medium resulted in increased formation of calcific nodules. Strikingly, IFN-α–mediated calcification was significantly higher in AVICs from males, and was blocked by tofacitinib, a JAK (Janus kinase) inhibitor, and by a BMP antagonist. A female-specific protective mechanism involving the activation of PI3K-Akt (protein kinase B) pathways and cell survival was disclosed. Females exhibited higher levels of
BCL2
in valve cells and tissues and lower annexin V staining on cell stimulation.

Conclusions—

IFN-α acts as a proinflammatory and pro-osteogenic cytokine in AVICs, its effects being potentiated by lipopolysaccharide. Results also uncovered sex differences with lower responses in female AVICs and sex-specific mechanisms involving apoptosis. Data point to JAK/STAT (signal transducer and activator of transcription) system as a potential therapeutic target for calcific aortic valve disease.
Detectability vs. time and costs in pooled DNA extraction of cutaneous swabs: a study on the amphibian chytrid fungi
Authors: Sabino-Pinto Joana , Krause E. Tobias , Bletz Molly C. , Martel An , Pasmans Frank , Steinfartz Sebastian , Vences Miguel
Published: July 2018

Epidemiology relies on understanding the distribution of pathogens which often can be detected through DNA-based techniques, such as quantitative Polymerase Chain Reaction (qPCR). Typically, the DNA of each individual sample is separately extracted and undergoes qPCR analysis. However, when performing field surveys and long-term monitoring, a large fraction of the samples is generally expected to be negative, especially in geographical areas still considered free of the pathogen. If pathogen detection within a population – rather than determining its individual prevalence – is the focus, work load and monetary costs can be reduced by pooling samples for DNA extraction. We test and refine a user-friendly technique where skin swabs can be pooled during DNA extraction to detect the amphibian chytrid fungi, Batrachochytrium dendrobatidis and B. salamandrivorans (Bsal). We extracted pools with different numbers of samples (from one to four swabs), without increasing reaction volumes, and each pool had one sample inoculated with a predetermined zoospore amount. Pool size did not reduce the ability to detect the two fungi, except if inoculated with extremely low zoospore amounts (one zoospore). We confirm that pooled DNA extraction of cutaneous swabs can substantially reduce processing time and costs without minimizing detection sensitivity. This is of relevance especially for the new emerging pathogen Bsal, for which pooled DNA extraction had so far not been tested and massive monitoring efforts in putatively unaffected regions are underway.
Flora of Singapore precursors, 4. A summary of scandent Psychotria (Rubiaceae) in Singapore and Peninsular Malaysia
Authors: TURNER I.M. , KUMAR V.S.
Published: July 2018

A total of 18 species of Psychotria with a climbing and/or hemi-epiphytic habit are enumerated as native to Peninsular Malaysia and Singapore. This number includes one newly described species, Psychotria deltata, known from Johore and Singapore; and one taxon raised to species rank, Psychotria euosma (based on Psychotria sarmentosa var. montana). A new record for Psychotria serpens from Peninsular Malaysia is presented, and a number of collections are tentatively placed in Psychotria chartacea, a species from Peninsular Thailand. Four species are added to the list of native taxa for Singapore. Psychotria kunstleri is synonymised with Psychotria ridleyi and P. cantleyi is reduced to P. scortechinii. Lectotypes are designated for nearly all names applied to climbing Psychotria taxa for Peninsular Malaysia and Singapore including the Linnaean species P. serpens.
Verrucaria tenebrosa (Verrucariaceae), a new lichen species from Finland and Norway, and notes on the taxonomy of epiphytic taxa belonging to the V. hydrophila complex
Authors: PYKÄLÄ JUHA , LAUNIS ANNINA , MYLLYS LEENA
Published: July 2018

Species related to Verrucaria hydrophila and V. placida in Finland were studied based on morphology and ITS sequences. V. tenebrosa is described as new. The species is characterized by a thin, variable-coloured thallus, small and rather sparsely occurring perithecia with a thin thalline cover, and relatively broad ascospores. V. tenebrosa occurs in shady habitats, usually on calcareous pebbles on N-facing cliffs. It has an eastern distribution in Finland, but it also occurs in Norway. The sequences of an epiphytic species V. lignicola were grouped together with V. hydrophila. However, based on morphological differences we consider them not to be conspecific, but suggest that V. hydrophila is a species complex in need of further studies. An epiphytic occurrence of V. hydrophila is confirmed by an ITS sequence. One putative sequence of V. trabicola is also grouped together with V. hydrophila, but further studies are needed on the identity of V. trabicola.
Resurrection and typification of Verbascum auriculatum (Scrophulariaceae), a long-disused name in Flora Graeca Sibthorpiana
Authors: ZOGRAFIDIS ARIS
Published: July 2018

Verbascum auriculatum, a name for a species discovered during Sibthorp’s first expedition in the Eastern Mediterranean, had long been sunk into synonymy of V. mucronatum. Surprisingly, however, the original material of this name was found not to match V. mucronatum but V. propontideum, a very distinct species, remarkably dissimilar to V. mucronatum. V. auriculatum is lectotypified and resurrected since V. propontideum represents a younger synonym. The species is endemic to the S.E. Aegean region, whereas Sibthorp has left no indication of where and when he collected the plant. A hypothesis on the possible locus classicus and date of the original collection is presented.
Three new Canuellidae (Copepoda: Canuelloida) from Iran
Authors: NAZARI F. , MIRSHAMSI O. , SARI A. , ALIABADIAN M. , ARBIZU P. MARTÍNEZ
Published: July 2018

A survey of copepods from intertidal zone of the Persian Gulf and the Gulf of Oman resulted in discovery of three new species belonging to the family Canuellidae Lang, 1944. This work contributes to the final aim to describe meiobenthic copepods from this region and is the first description of meiobenthic copepods from Iranian coastline. The new species belong to the genera Brianola Monard, 1926, Canuella, T. & A. Scott, 1893, and Scottolana Huys, 2009. Compared to other congeners, Brianola haliensis sp. nov. is unique in the armature of the first leg, number of segments and setation of the antennary endopod and exopod. Canuella persica sp. nov. is easily distinguishable from its congeners by the shape of furcal rami and male genitalia. Scottolana gomezi sp. nov. is assigned to the longipes-group by the presence of two and three post-genital somites in the female and male, respectively. It is closely related to S. geei (Mu & Huys, 2004) recorded from the Bohai Sea, China, but can be distinguished by its eight-segmented antennary exopod, mouthparts setation, and shape of the furcal rami.
Notes on the shrimp genus Palaemon Weber, 1795 (Crustacea, Decapoda, Palaemonidae) and related genera from Taiwan
Authors: ASHELBY CHRISTOPHER W. , LIN WEI-CHENG , GRAVE SAMMY DE , CHAN TIN-YAM
Published: July 2018

The shrimp genus Palaemon Weber, 1795 and its related genera in Taiwan are reviewed based on newly collected specimens, whilst older records are critically reviewed. Five genera and 11 species are now known to occur in Taiwan, although there are no recent records for Palaemon modestus (Heller, 1862), which could be nationally extinct. The records of P. debilis Dana, 1852 and Nematopalaemon tenuipes (Henderson, 1893) in Taiwan are confirmed. Three genera, namely Brachycarpus Spence Bate, 1888, Leander Desmarest, 1849 and Leandrites Holthuis, 1950, each with one species are reported for the first time from Taiwan.
A new species of Aschistophleps from Thailand and Laos, with a new generic synonymy (Lepidoptera, Sesiidae)
Authors: KALLIES AXEL , ŠTOLC VLADIMÍR
Published: July 2018

We here describe a new clearwing moth species, Aschistophleps ignisquamulata sp. nov., from northern Thailand and Laos. This striking new species differs from all other species of Osminiini in both external appearance and genitalia and displays characteristics that indicate that Pyrophleps Arita & Gorbunov is a junior subjective synonym of Aschistophleps (syn. nov.).
A new bent-toed gecko (Squamata: Gekkonidae: Cyrtodactylus) from the Western Himalayas, Himachal Pradesh, India
Authors: AGARWAL ISHAN , KHANDEKAR AKSHAY , BAUER AARON M.
Published: July 2018

We describe a new species of the gekkonid genus Cyrtodactylus based on a series of six specimens from the Chamba Valley in the Western Himalayas, Himachal Pradesh state, India. Cyrtodactylus chamba sp. nov. is a member of the subgenus Siwaligekko and can be diagnosed from congeners in the Western Himalayas by a combination of its small size (snout to vent length up to 63 mm), a continuous series of five precloacal pores on males, 13–15 rows of dorsal tubercles, 33–43 scales across the belly, no regular series of enlarged subcaudals, and a dorsal colour pattern of 5–7 irregular, broad, dark bands with much narrower, light interspaces. The new species is 14% divergent in ND2 sequence from the most similar sampled congener, Cyrtodactylus (Siwaligekko) himalayanus from Jammu and Kashmir, and is 0.5–1.1% divergent in nuclear sequence data from sampled Siwaligekko species. Many more undiscovered Cyrtodactylus species probably exist across the Himalayas at elevations below ~2000 m; basic field surveys for reptiles and other poorly known groups and examination of existing material should be a priority if we are to appreciate the true diversity of this spectacular mountainous landscape.