bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Parameters of 18F-FDG PET/CT in Patients with Primary Testicular Diffuse Large B-Cell Lymphoma
Authors: Yang Jing , Zhu Sha , Pang Fuwen , Xu Miao , Dong Yiting , Hao Jianqi , Ma Xuelei
Published: September 2018

Fluorine-18 fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT), a hybrid imaging technique that simultaneously provides functional and anatomical information, has been reported to be useful in lymphoma. The present study was to evaluate the functional parameters of 18F-FDG PET/CT in patients with testicular diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed medical records of 5095 patients with lymphoma who treated at West China Hospital between March 2003 and January 2017, and selected patients with 18F-FDG PET/CT findings and subsequently biopsy confirmed the invasion of testis with DLBCL. Maximum standardized uptake values (SUVmax), peak standardized uptake values (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the patients were measured. We evaluated the characteristics of 18F-FDG PET/CT in this population. Six patients ranged in age from 37 to 73 years (median age, 58 years) were included in the analysis. The mean SUVmax was 11.09 and varied between 7.20 and 19.75; mean SUVpeak was 9.56 and ranged between 6.79 and 14.39. In addition, mean MTV 42% was 18.4 and varied between 1.3 and 61.6; mean MTV 2.5 was 34.7 and varied significantly between 1.6 and 141.9. With regard to TLG, mean TLG 42% was 168.906 and ranged from 7.514 to 687.004, while mean TLG 2.5 was 253.972 and ranged from 8.400 to 1127.802. In conclusion, 18F-FDG PET/CT scan is a useful tool in patients with testicular DLBCL. SUV, MTV, and TLG may vary a lot in different patients. SUVmax of testicular DLBCL lesion is relatively higher than that of normal testis. Also, we provided a set of MTV and TLG data and firstly showed their significant correlation with overall survival, which indicated a potential prognostic value of MTV and TLG. However, studies with larger population are needed to confirm these findings.
Comparison of Oral Collection Methods for Studies of Microbiota
Authors: Vogtmann Emily , Chen Jun , Kibriya Muhammad G. , Amir Amnon , Shi Jianxin , Chen Yu , Islam Tariqul , Eunes Mahbubul , Ahmed Alauddin , Naher Jabun , Rahman Anisur , Barmon Bhaswati , Knight Rob , Chia Nicholas , Ahsan Habibul , Abnet Christian C. , Sinha Rashmi
Published: September 2018

Background:

A number of cohort studies have collected Scope mouthwash samples by mail, which are being used for microbiota measurements. We evaluated the stability of Scope mouthwash samples at ambient temperature and determined the comparability of Scope mouthwash with saliva collection using the OMNIgene ORAL Kit.

Methods:

Fifty-three healthy volunteers from Mayo Clinic and 50 cohort members from Bangladesh provided oral samples. One aliquot of the OMNIgene ORAL and Scope mouthwash were frozen immediately and one aliquot of the Scope mouthwash remained at ambient temperature for 4 days and was then frozen. DNA was extracted and the V4 region of the 16S rRNA gene was PCR amplified and sequenced using the HiSeq. Intraclass correlation coefficients (ICC) were calculated.

Results:

The overall stability of the Scope mouthwash samples was relatively high for alpha and beta diversity. For example, the meta-analyzed ICC for the Shannon index was 0.86 (95% confidence interval, 0.76–0.96). Similarly, the ICCs for the relative abundance of the top 25 genera were generally high. The comparability of the two sample types was relatively low when measured using ICCs, but were increased by using a Spearman correlation coefficient (SCC) to compare the rank order of individuals.

Conclusions:

Overall, the Scope mouthwash samples appear to be stable at ambient temperature, which suggests that oral rinse samples received by the mail can be used for microbial analyses. However, Scope mouthwash samples were distinct compared with OMNIgene ORAL samples.

Impact:

Studies should try to compare oral microbial metrics within one sample collection type.
Epigenetically Silenced Candidate Tumor Suppressor Genes in Prostate Cancer: Identified by Modeling Methylation Stratification and Applied to Progression Prediction
Authors: Zhang Wensheng , Flemington Erik K. , Deng Hong-Wen , Zhang Kun
Published: September 2018

Background:

Recent studies have shown that epigenetic alterations, especially the hypermethylated promoters of tumor suppressor genes (TSGs), contribute to prostate cancer progression and metastasis. This article proposes a novel algorithm to identify epigenetically silenced TSGs (epi-TSGs) for prostate cancer.

Methods:

Our method is based on the perception that the promoter CpG island(s) of a typical epi-TSG has a stratified methylation profile over tumor samples. In other words, we assume that the methylation profile resembles the combination of a binary distribution of a driver mutation and a continuous distribution representing measurement noise and intratumor heterogeneity.

Results:

Applying the proposed algorithm and an existing method to The Cancer Genome Atlas prostate cancer data, we identify 57 candidate epi-TSGs. Over one third of these epi-TSGs have been reported to carry potential tumor suppression functions. The negative correlations between the expression levels and methylation levels of these genes are validated on external independent datasets. We further find that the expression profiling of these genes is a robust predictive signature for Gleason scores, with the AUC statistic ranging from 0.75 to 0.79. The identified signature also shows prediction strength for tumor progression stages, biochemical recurrences, and metastasis events.

Conclusions:

We propose a novel method for pinpointing candidate epi-TSGs in prostate cancer. The expression profiling of the identified epi-TSGs demonstrates significant prediction strength for tumor progression.

Impact:

The proposed epi-TSGs identification method can be adapted to other cancer types beyond prostate cancer. The identified clinically significant epi-TSGs would shed light on the carcinogenesis of prostate adenocarcinomas.
For Whom the Cell Tolls? Intratumoral Treatment Links Innate and Adaptive Immunity
Authors: Marquez-Rodas Ivan , Aznar María Angela , Calles Antonio , Melero Ignacio
Published: September 2018

Intratumoral immunotherapy can potentially modulate the tumor microenvironment (TME) and potentiate the effects of concomitant or sequential systemic immunotherapies. Intratumoral administration of different Toll-like receptor agonists, including TLR4, can potentiate these effects through innate and adaptive immunity connection.

See related article by Bhatia et al., p. 1185
C9orf72 Protein Plasmatic Concentrations Are Similar between C9ORF72 Expansion Carriers and Noncarriers in Frontotemporal Dementia
Authors: Fourier Anthony , Formaglio Maité , Sauvée Mathilde , Perret-Liaudet Armand , Latour Philippe , Bost Muriel , Quadrio Isabelle
Published: September 2018

Background/Aims: The aim of the study was to assess the theory of haploinsufficiency in C9ORF72 expansion carriers, the most frequent causative gene of frontotemporal dementia. Methods: Plasmatic concentrations of C9orf72 protein were measured in 33 patients suspected of familial frontotemporal dementia using an enzyme-linked immunosorbent assay. Results: No difference was observed between C9ORF72 expansion carriers (21.2% of patients) and noncarriers (78.8% of patients). C9orf72 protein determination is not a suitable biomarker for screening C9ORF72 expansion carriers. Conclusion: Our results provide new evidence against the hypothesis of haploinsufficiency leading to frontotemporal dementia in C9ORF72 expansion carriers.
Bile Cast Nephropathy: A Pathologic Finding with Manifold Causes Displayed in an Adult with Alcoholic Steatohepatitis and in a Child with Wilson’s Disease
Authors: Torrealba Jose , Sweed Nathan T. , Burguete Daniel , Hendricks Allen R.
Published: September 2018

Bile cast nephropathy (BCN) is seen in patients who have acute kidney injury and severe hyperbilirubinemia due to a wide range of hepatobiliary system diseases. Findings seen by renal biopsy include acute tubular injury with necrotic and sloughed epithelial cells, yellow-green pigment within tubular epithelial cells, and pigmented granular casts. Hall’s special stain for bile turns these casts green. In recent years, BCN has been described in a small number of case reports and clinical studies primarily in the setting of severe liver dysfunction. We present 2 diverse cases of BCN. The first involves an adult with hepatorenal syndrome secondary to alcoholic steatohepatitis and early cirrhosis. Second, we describe the first reported case of BCN in a child with fulminant hepatic failure due to Wilson’s disease. Our cases expand the spectrum of causative diseases, and they provide further evidence that BCN is a distinct pathologic entity which may be found in both adult and pediatric patients with a variety of severe liver diseases.
A Novel Synthesized Sulfonamido-Based Gallate-JEZTC Blocks Cartilage Degradation on Rabbit Model of Osteoarthritis: An in Vitro and in Vivo Study
Authors: Lu Zhenhui , Liu Qin , Liu Lei , Wu Huayu , Zheng Li , Zhao Jin-min
Published: September 2018

Background/Aims: 3, 4, 5-trihydroxy-N-{4-[(5-methylisoxazol-3-yl) sulfamoyl] phenyl} benzamide (JEZTC), synthesized from gallic acid (GA) and sulfamethoxazole (SMZ), was reported with chondroprotective effects. However, the effects of JEZTC on osteoarthritis (OA) are still unclear. The goal of this study was to investigate the anti-osteoarthritic properties of JEZTC on interleukin-1-beta (IL-1β) stimulated chondrocytes in vitro and a rabbit anterior cruciate ligament transaction (ACLT) OA model in vivo. Methods: Changes in matrix metalloproteinases (MMPs) and apoptosis genes (bax, caspase 3 and tnf-α) and OA-specific protein (MMP-1) expression in vitro and in vivo were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. The production of reactive oxygen species (ROS) were investigated upon the treatment of JEZTC in chondrocytes processed with IL-1β in vitro and OA in vivo. Effect of JEZTC on OA was further studied by the macroscopic and histological evaluation and scores. The key proteins in signaling pathways inMAPK/P38, PI3KAkt and NF-κB also determined using western blot (WB) analysis. Results: JEZTC could significantly suppress the expression of MMPs and intracellular ROS, while meaningfully increase the gene expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). Moreover, there was less cartilage degradation in JEZTC group compared with the phosphate-buffered saline (PBS) group in vivo. Results also indicated that JEZTC exerts effect on OA by regulating MAPKs and PI3K/Akt signaling pathways to activate NF-κB pathway, leading to the down-regulation of MMPs. The chondro-protective effect of JEZTC may be related with its ability to inhibit chondrocyte apoptosis by reduction of ROS production. Conclusion: JEZTC may be a possible therapeutic agent in the treatment of OA.
Sustained Release of IGF-1 by 3D Mesoporous Scaffolds Promoting Cardiac Stem Cell Migration and Proliferation
Authors: Sun Yuning , Han Xiqiong , Wang Xin , Zhu Boqian , Li Bing , Chen Zhongpu , Ma Genshan , Wan Mimi
Published: September 2018

Background/Aims: C-kit-positive cardiac stem cells (CSCs) may have potential as a treatment for cardiovascular disease. However, the low survival rates of c-kit-positive CSCs present a major challenge during the transplantation process. Methods: The hierarchical structure of the 3D cell scaffold was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and N2 adsorption-desorption isotherms. Analyses of the proliferation and migration performances of the IGF-1 scaffold on c-kit-positive CSCs were conducted by experiments including QuantiT PicoGreen dsDNA and transwell assays. Results: In this study, we synthesized for the first time a novel hierarchical macro-mesoporous silica material (denoted MS15-c) in a one-pot procedure for the release of insulin-like growth factor-1 (IGF-1) and a three-dimensional (3D) cell scaffold. Both macropores and mesopores were visible in MS15-c and enabled the sustained release of IGF-1, extending its half-life and enhancing CSC proliferation and migration. Proliferation and migration were detected by QuantiT PicoGreen dsDNA and transwell assays, respectively. Moreover, an in vivo experiment was conducted to detect heart function with the addition of MS15-c. The new strategy proposed in this paper may extend the bio-applications of 3D cell scaffolds, thus permitting the sustained release of growth factors and efficient promotion of cell proliferation. Conclusion: This work successfully demonstrated an effective strategy for the construction of MS15-c cell scaffolds with hierarchical macro-mesoporous structures. The macro-mesoporous structures gave cell scaffolds the ability to release a growth factor to facilitate cell growth, while the scaffold structure promoted cell proliferation.
Catalase Enhances Viability of Human Chondrocytes in Culture by Reducing Reactive Oxygen Species and Counteracting Tumor Necrosis Factor-α-Induced Apoptosis
Authors: Li Siming , Yang Xiaohong , Feng Zhencheng , Wang Pengzhen , Zhu Weicong , Cui Shuliang
Published: September 2018

Background/Aims: Both physiologic remodeling and pathologic regeneration of cartilage tissue rely upon chondrocyte functions and are benefited from factors that promote viability and inhibit apoptosis of the cell, and associated mechanisms. High level of reactive oxygen species (ROS) and proinflammatory cytokines activate apoptosis signaling and initiate cell death, which can be attenuated by antioxidants. This study examined the effect of catalase (CAT) on ROS and tumor necrosis factor-α (TNF-α)-induced apoptosis in human C28/I2 chondrocytes cultured in monolayer. Methods: Chondrocytes were treated with diluted CAT in the presence or absence of TNF-α and compared to untreated cells. Levels of hydrogen peroxide (H2O2) and mitochondrial membrane potential (Δψm) were measured using fluorescent labeling, cell apoptosis was assayed by flow cytometry using Annexin V/propidium iodide (PI) staining, gene expression was detected by quantitative real time polymerase chain reaction (qRT-PCR) and the proteins were investigated by Western blotting. Results: CAT effectively reduced the intracellular ROS caused by the monolayer culture system, enhanced the Δψm depending on the presence of TNF-α and promoted morphological features at sub-cellular level. CAT also attenuated the TNF-α-upregulated expression of factors/mediators of extrinsic cell death cascade and apoptotic caspases, ultimately resulted in promoted cellular viability. Conclusion: The anti-apoptotic effect of CAT on chondrocytes via scavenging ROS and suppressing TNF-α-induced cell apoptosis by TNF/TNF receptor (TNFR) mediated death signaling pathway and potentiate CAT as a complementary agent beneficial to cartilage remodeling and regeneration in vivo, and cell-based therapies of cartilage repair demanding viable cells expanded ex vivo.
Juniperus Communis Extract Exerts Antitumor Effects in Human Glioblastomas Through Blood-Brain Barrier
Authors:   Tsai, Tsai Nu-Man , Chang Kai-Fu , Wang Jun-Cheng
Published: September 2018

Background/Aims: Herbal materials derived from Juniperus communis (JCo) possess anticancer activity. In this study, we evaluated the efficacy of a JCo berry extract in suppressing glioblastoma growth. Methods: The effects of JCo extract on the viability of normal and glioma cell lines was analyzed using a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The synergistic therapeutic effect of JCo extract and temozolomide (TMZ) on glioma cells was examined by MTT analysis. Flow cytometry analysis, the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) test, and western blotting were performed to identify the apoptotic pathway. To determine the in vivo efficacy of the JCo extract, rats were injected with 5 × 104 rat glioma RG2 cells in the back skin and brain hemisphere and then received a subcutaneous injection in the back skin that contained either JCo extract or vehicle. Finally, blood and histologic examinations were performed to evaluate JCo toxicity. Results: The IC50 values of JCo extract were 57–69 µg/mL and 49–67 µg/mL in the glioblastoma cell lines after 24 and 48 h, respectively. However, in non-tumor cell lines, the respective IC50 values of JCo extract were 76–105 µg/mL and 77–108 µg/mL. The JCo extract had a stronger cytotoxicity and a larger range of IC50 values in glioma than in normal cells as compared to those effects caused by temozolomide (TMZ). In addition, the results of flow cytometry analysis, TUNEL test, and western blotting revealed that the JCo extract induced glioma cell cycle arrest through intrinsic and extrinsic apoptotic pathways. In the in vivo studies, a significant reduction of tumor size in JCo-treated rats, as measured by animal MRI, demonstrated that the JCo extract effectively inhibited glioma cell growth and successfully penetrated the blood-brain barrier. The immunohistochemical (IHC) staining detected positive signals of PCNA, VEGFR-1, and VEGFR -2 in 44.49%, 5.88%, and 5.85% of JCo-treated glioma cells, respectively. However, positive signals of PCNA, VEGFR-1, and VEGFR-2 were detected in 73.08%, 9.67%, and 11.70% of vehicle-treated glioma cells, respectively. The IHC examination of PCNA and VEGFR-1 and -2 indicated that JCo extract significantly decreased the degree of neovascularization. However, no significant differences in serum levels of blood cell count and hepatic enzymes, renal function index, and the histologic appearance of vital organs were detected between the JCo and vehicle-treated rats. Conclusion: The JCo extract penetrated the blood-brain barrier and significantly induced glioma cell apoptosis by reducing neovascularization via suppression of the PI3K/AKT/mTOR pathway. Furthermore, JCo extract was less cytotoxic to non-neoplastic vital organs than TMZ.
The Nuclear Translocation of Mitogen-Activated Protein Kinases: Molecular Mechanisms and Use as Novel Therapeutic Target
Authors: Flores Karen , Yadav Suresh Singh , Katz Arieh A. , Seger Rony
Published: September 2018

The mitogen-activated protein kinase (MAPK) cascades are central signaling pathways that play a central role in the regulation of most stimulated cellular processes including proliferation, differentiation, stress response and apoptosis. Currently 4 such cascades are known, each termed by its downstream MAPK components: the extracellular signal-regulated kinase 1/2 (ERK1/2), cJun-N-terminal kinase (JNK), p38 and ERK5. One of the hallmarks of these cascades is the stimulated nuclear translocation of their MAPK components using distinct mechanisms. ERK1/2 are shuttled into the nucleus by importin7, JNK and p38 by a dimer of importin3 with either importin9 or importin7, and ERK5 by importin-α/β. Dysregulation of these cascades often results in diseases, including cancer and inflammation, as well as developmental and neurological disorders. Much effort has been invested over the years in developing inhibitors to the MAPK cascades to combat these diseases. Although some inhibitors are already in clinical use or clinical trials, their effects are hampered by development of resistance or adverse side-effects. Recently, our group developed 2 myristoylated peptides: EPE peptide, which inhibits the interaction of ERK1/2 with importin7, and PERY peptide, which prevents JNK/p38 interaction with either importin7 or importin9. These peptides block the nuclear translocation of their corresponding kinases, resulting in prevention of several cancers, while the PERY peptide also inhibits inflammation-induced diseases. These peptides provide a proof of concept for the use of the nuclear translocation of MAPKs as therapeutic targets for cancer and/or inflammation.
СТАН КОМОРБІДНОЇ ПАТОЛОГІЇ У ХВОРИХ НА МОРБІДНЕ ОЖИРІННЯ
Authors: Todurov I. M. , Perekhrestenko O. V. , Kalashnikov O. O. , Kosyukhno S. V. , Yakimets V. M. , Plehutsa O. I. , Potapov O. A.
Published: September 2018

Мета: покращити результати лікування хворих на морбідне ожиріння шляхом оцінки частоти розвитку та особливостей супутньої патології.Матеріали і методи. Проаналізовано результати передопераційного клініко-лабораторного та інструментального обстеження 205 хворих на морбідне ожиріння.Результати. Супутні захворювання діагностовано у 203 (99 %) хворих на морбідне ожиріння, включених у дослідження. В структурі супутньої патології переважали захворювання серцево-судинної системи у 135 (65,8  %) хворих, порушення вуглеводного – в 135 (65,8 %) пацієнтів та ліпідного обміну – в 161 (78,5 %) хворого, що віддзеркалюють патогенетичну сутність метаболічного синдрому та суттєво підвищують ризик передчасної смерті. Захворювання дихальної системи діагностовано у 63 (30,7 %) хворих, системи травлення – у 130 (63,4 %) пацієнтів.Висновки. Характерною особливістю хворих на морбідне ожиріння є висока частота, системність та, в більшості випадків, мультифокальність органних уражень, що вимагає системної реалізації мультидисциплінарного підходу для покращення результатів лікування означеної категорії пацієнтів.
ОРГАНІЗАЦІЯ МЕДИКО-САНІТАРНОЇ ДОПОМОГИ ХВОРИМ НА ХРОНІЧНИЙ ПАНКРЕАТИТ ТА ЇХ РЕАБІЛІТАЦІЯ
Authors: Trehub P. O.
Published: September 2018

Мета: вивчити та охарактеризувати чинники, які зумовлюють якість надання медичної допомоги хворим на хронічний панкреатит та їх реабілітації.Матеріали і методи. Проведено соціологічне опитування, за розробленими анкетами, 300 хворих на хронічний панкреатит та викопіювання даних із медичної документації: статистичних карт хворих, які вибули зі стаціонару (форма № 066/о).Результати. Встановлено, що пацієнтам, які хворіють на хронічний панкреатит, недостатньо проводять реабіліта­ційні заходи, так відсоток охоплення проведеного оздоровлення в санаторії склав лише (34,7±2,8) % хворих, недостат­ність знань із організації харчування, де лише (50,3±2,9) % у повному обсязі володіють необхідною інформа­цією, ранкову гімнастику виконують лише (64,0±2,8) %, фізіотерапевтичні методи застосовують тільки (62,7±2,8) %.Висновки. Отримані дані підтверджують необхідність оптимізації системи надання медико-профілактичної допомоги хворим на хронічний панкреатит та їх реабілітації.
USP20 (Ubiquitin-Specific Protease 20) Inhibits TNF (Tumor Necrosis Factor)-Triggered Smooth Muscle Cell Inflammation and Attenuates Atherosclerosis
Authors: Jean-Charles Pierre-Yves , Wu Jiao-Hui , Zhang Lisheng , Kaur Suneet , Nepliouev Igor , Stiber Jonathan A. , Brian Leigh , Qi Rui , Wertman Virginia , Shenoy Sudha K. , Freedman Neil J.
Published: September 2018

Objective—

Signaling that activates NFκB (nuclear factor κB) in smooth muscle cells (SMCs) is integral to atherosclerosis and involves reversible ubiquitination that activates proteins downstream of proatherogenic receptors. Deubiquitination of these proteins is mediated by USP20 (ubiquitin-specific protease 20), among other deubiquitinases. We sought to determine whether USP20 activity in SMCs decreases atherosclerosis.

Approach and Results—

To address this question, we used male
Ldlr
−/−
mice without (control) or with SMC-specific expression of murine USP20 (SMC-USP20-transgenic) or its dominant-negative (DN; C154S/H643Q) mutant (SMC-DN-USP20-transgenic). Before the appearance of intimal macrophages, NFκB activation in aortic medial SMCs was greater in SMC-DN-USP20-transgenic than in control mice. After 16 weeks on a Western diet, SMC-DN-USP20-transgenic mice had 46% greater brachiocephalic artery atheroma area than control mice. Congruently, aortic atherosclerosis assessed en face was 21% greater than control in SMC-DN-USP20-transgenic mice and 13% less than control in SMC-USP20-transgenic mice. In response to TNF (tumor necrosis factor), SMCs from SMC-DN-USP20-transgenic mice showed ≈3-fold greater NFκB activation than control SMCs. Silencing USP20 in SMCs with siRNA (small interfering RNA) augmented NFκB activation by ≈50% in response to either TNF or IL-1β (interleukin-1β). Coimmunoprecipitation experiments revealed that USP20 associates with several components of the TNFR1 (TNF receptor-1) signaling pathway, including RIPK1 (receptor-interacting protein kinase 1), a critical checkpoint in TNF-induced NFκB activation and inflammation. TNF evoked ≈2-fold more RIPK1 ubiquitination in SMC-DN-USP20-transgenic than in control SMCs, and RIPK1 was deubiquitinated by purified USP20 in vitro.

Conclusions—

USP20 attenuates TNF- and IL-1β–evoked atherogenic signaling in SMCs, by deubiquitinating RIPK1, among other signaling intermediates.
NBEAL2 (Neurobeachin-Like 2) Is Required for Retention of Cargo Proteins by α-Granules During Their Production by Megakaryocytes
Authors: Lo Richard W. , Li Ling , Leung Richard , Pluthero Fred G. , Kahr Walter H.A.
Published: September 2018

Objective—

Human and mouse megakaryocytes lacking NBEAL2 (neurobeachin-like 2) produce platelets where α-granules lack protein cargo. This cargo is mostly megakaryocyte-synthesized, but some proteins, including FGN (fibrinogen), are endocytosed. In this study, we examined the trafficking of both types of cargo within primary megakaryocytes cultured from normal and NBEAL2-null mice, to determine the role of NBEAL2 in α-granule maturation. We also examined the interaction of NBEAL2 with the granule-associated protein P-selectin in human megakaryocytes and platelets.

Approach and Results—

Fluorescence microscopy was used to compare uptake of labeled FGN by normal and NBEAL2-null mouse megakaryocytes, which was similar in both. NBEAL2-null cells, however, showed decreased FGN retention, and studies with biotinylated protein showed rapid loss rather than increased degradation. Intracellular tracking via fluorescence microscopy revealed that in normal megakaryocytes, endocytosed FGN sequentially associated with compartments expressing RAB5 (Ras-related protein in brain 5), RAB7 (Ras-related protein in brain 7), and P-selectin, where it was retained. A similar initial pattern was observed in NBEAL2-null megakaryocytes, but then FGN passed from the P-selectin compartment to RAB11 (Ras-related protein in brain 11)-associated endosomes before release. Megakaryocyte-synthesized VWF (Von Willebrand factor) was observed to follow the same route out of NBEAL2-null cells. Immunofluorescence microscopy revealed intracellular colocalization of NBEAL2 with P-selectin in human megakaryocytes, proplatelets, and platelets. Native NBEAL2 and P-selectin were coimmunoprecipitated from platelets and megakaryocytes.

Conclusions—

NBEAL2 is not required for FGN uptake by megakaryocytes. NBEAL2 is required for the retention of both endocytosed and megakaryocyte-synthesized proteins by maturing α-granules, and possibly by platelet-borne granules. This function may involve interaction of NBEAL2 with P-selectin.
Small GTPase Rap1A/B Is Required for Lymphatic Development and Adrenomedullin-Induced Stabilization of Lymphatic Endothelial Junctions
Authors: Xu Wenjing , Wittchen Erika S. , Hoopes Samantha L. , Stefanini Lucia , Burridge Keith , Caron Kathleen M.
Published: September 2018

Objective—

Maintenance of lymphatic permeability is essential for normal lymphatic function during adulthood, but the precise signaling pathways that control lymphatic junctions during development are not fully elucidated. The G
s
-coupled AM (adrenomedullin) signaling pathway is required for embryonic lymphangiogenesis and the maintenance of lymphatic junctions during adulthood. Thus, we sought to elucidate the downstream effectors mediating junctional stabilization in lymphatic endothelial cells.

Approach and Results—

We knocked-down both
Rap1A
and
Rap1B
isoforms in human neonatal dermal lymphatic cells (human lymphatic endothelial cells) and genetically deleted the
mRap1
gene in lymphatic endothelial cells by producing 2 independent, conditional
Rap1a/b
knockout mouse lines.
Rap1A/B
knockdown caused disrupted junctional formation with hyperpermeability and impaired AM-induced lymphatic junctional tightening, as well as rescue of histamine-induced junctional disruption. Less than 60% of lymphatic-
Rap1a/b
knockout embryos survived to E13.5 exhibiting interstitial edema, blood-filled lymphatics, disrupted lymphovenous valves, and defective lymphangiogenesis. Consistently, inducible lymphatic-
Rap1a/b
deletion in adult animals prevented AM-rescue of histamine-induced lymphatic leakage and dilation.

Conclusions—

Rap1 (Ras-related protein) serves as the dominant effector downstream of AM to stabilize lymphatic junctions. Rap1 is required for maintaining lymphatic permeability and driving normal lymphatic development.
The Pain of Being Hybrid: Catholic Writers and Political Islam in Postcolonial Indonesia
Authors: Laksana Albertus Bagus
Published: September 2018

Informed by postcolonial theories and approaches, and based on the works of three Indonesian Catholic writers, this essay looks at the ways in which these writers address the question of identity. They propose the notion of hybrid identity where the identity of the nation is built upon different layers of racial, ethnic, and religious belongings, and loyalties to local tradition and aspirations for modernity. While this notion of identity is inspired by the framework of “catholicity”, it is also “postcolonial” for a number of reasons. First, its formation betrays traces of colonial conditions and negotiations of power. Second, it reflects the subject position of these writers as Indonesian natives who embraced a religion that has complex ties to European colonialism and problematic relations with Islam. Third, it criticizes the post-colonial state and society, which perpetuate many of the ills of the colonial political system, including racism and the abuse of power. Their discourse also reveals the pain of being hybrid, mainly in their inability to appropriately tackle the question of political Islam. The recent political upheaval reveals the need for more creative engagement with political Islam in order for this hybrid identity to work.
A new species of Astrochapsa (Graphidaceae) from Martinique, with a world-wide key to the species
Authors: BORGATO LUCA , ERTZ DAMIEN
Published: September 2018

Astrochapsa martinicensis is described as new to science. It is characterized by a whitish-farinose thallus, 6–8-spored asci, (4–)5–7(–9)-septate ascospores of (12.5–)14–24(–29) × (4.5–)5–6.5(–7) µm and a chemistry with one terpenoid and traces of UV+ substances. The new species was discovered among lichen specimens collected in 2013 on the island of Martinique (Lesser Antilles). A phylogenetic analysis using nuLSU sequences places the new species in the genus Astrochapsa, as sister species to an unidentified specimen from Venezuela. An identification key to all currently accepted Astrochapsa species is provided.
On validation and typification of the name Festuca ×polovina (Poaceae): a correction and comments on indication of types of names of new taxa
Authors: MOSYAKIN SERGEI L. , SOKOLOVA IRINA V. , FEDORONCHUK MYKOLA M.
Published: September 2018

The controversial issue of valid publication and typification of the name Festuca ×polovina Bednarska (Poaceae) is discussed. It was assumed until recently that the name was published in 2009 invalidly because the author of the original description failed to cite the type (holotype) specimen. However, she indicated in the protologue that the holotype is deposited in the LWKS herbarium and mentioned the geographic origin of the taxon (Western Polissya of Ukraine). By this indication Bednarska fulfilled the requirements of Art. 40.6 and 40.7 of the ICN, and thus validly published the name. Fedoronchuk et al. (2010) cited the label of the supposed holotype in LWKS but did not mention the existence of three other duplicates in the same herbarium. Thus, Fedoronchuk et al. (2010) in fact cited the syntypes of the name. The specimen LWKS0030041 (cited as the “holotype” by Bednarska and Nachychko 2018) is designated here as the lectotype of the name F ×polovina. It is concluded that a proposal to amend the ICN is desirable for ensuring explicit citation and unambiguous indication of types (in particular, holotypes) for names of newly described taxa.
Utricularia sunilii (Lentibulariaceae), a striking new species from southern Western Ghats, Kerala, India
Authors: KUMAR VANNARATTA VEETTIL NAVEEN , PRABHUKUMAR KONICKAL MAMBETTA , JAGADEESAN RAVEENDRAN , HARINARAYANAN CHERUPPOYILATH  MANA , NAIR MAYA C. , JANARTHANAM MALAPATI K. , BALACHANDRAN INDIRA
Published: September 2018

Utricularia sunilii, a new species of Utricularia Sect. Oligocista from Kerala state of Western Ghats is described here. The new species shows similarities with U. graminifolia in having 3-nerved foliar organs and thickened capsule wall along the margin of dehiscence but differs by deeply 3-lobed lower lip of corolla.
Synopsis of the shore bugs of China (Hemiptera: Heteroptera: Leptopodomorpha: Saldidae)
Authors: VINOKUROV NIKOLAI N. , CAI WANZHI , CHEN PING-PING
Published: September 2018

In China, most research on shore bugs (Hemiptera: Leptopodomorpha: Saldidae) has been conducted intermittently during the second half of the 19th century. Records from the literature supplemented by our collections were used to construct an annotated list of 50 species in 13 genera and 2 subfamilies (Chiloxanthinae and Saldinae) of Saldidae now known from China. This paper also presents new distributional records and color plates depicting 26 species. Further, a list of 12 species of Saldidae known in neighboring territories that might occur in China is presented.
A taxonomic review of the parasitoid wasp genera Furcidentia Zettel and Pseudophanerotoma Zettel (Hymenoptera: Braconidae: Cheloninae) from the Neotropics with the description of four new species
Authors: KITTEL REBECCA N.
Published: September 2018

Furcidentia Zettel, 1990 (Braconidae: Cheloninae) from the New World has been recently recognised as a genus separate from Pseudophanerotoma Zettel, 1990. Previously known from three species, three additional new species of Furcidentia are described here from the Neotropical region: F. jenningsi sp. nov. (French Guiana), F. llama sp. nov. (Guatemala), and F. tikalensis sp. nov. (Guatemala). The species F. clypeata Zettel (Ecuador) comb. nov., F. pulchra Zettel (Costa Rica) comb. nov., and F. sharkeyi Zettel (Ecuador) comb. nov. are transferred to Furcidentia. Additionally, one new species of Pseudophanerotoma is described: P. austini sp. nov. (Guatemala), while P. paranaensis (Costa Lima) (Brazil) and P. thapsina (Walley) (Texas, USA) are redescribed and are here recorded from French Guiana for the first time, thus considerably expanding their known distribution. Redescriptions include the description of the male of P. thapsina (Walley) for the first time and of the female of P. paranaensis (Costa Lima). Identification keys to the Neotropical genera of Phanerotomini and the species of Furcidentia and Pseudophanerotoma are provided.
First Australian records of Ethusina (Crustacea: Decapoda: Ethusidae) and additional records from New Zealand
Authors: AHYONG SHANE T. , FARRELLY CAROLINE A.
Published: September 2018

Deep water ethusid crabs, genus Ethusina, are confirmed for the first time from Australia, with additional distribution records from New Zealand waters. Prior to the present study, Ethusina was reported from Australia on the basis of a single unidentified species from southwestern Australia. Four species are reported herein: Ethusina castro Ahyong, 2008, E. ciliacirrata Castro, 2005, E. robusta (Miers, 1886), and E. rowdeni Ahyong, 2008. Ethusina castro, previously known only from the female holotype from northern New Zealand is reported for the first time from eastern Australia, the Lord Howe Rise and Monowai Caldera, including the first known males. Ethusina ciliacirrata, described from Vanuatu, is confirmed from the Coral Sea and southwestern Australia. Ethusina rowdeni, from New Zealand, and the widespread E. robusta are recorded for the first time from Australia.
A new whitefly genus and species, Aleuroparvus theae Dubey (Hemiptera: Aleyrodidae) colonising Assam tea (Camellia sinensis) and Cinnamomum bejolghota, in North-East India
Authors: DUBEY ANIL KUMAR
Published: September 2018

Puparia of a new whitefly genus and species, Aleuroparvus theae Dubey gen. et sp. nov. are described along with drawings, habitus and type images of habitus and types, and scanning electron microscope microphotographs. It is found infesting an economically important plant, Assam tea, Camellia sinensis (L.) (Theaceae) in Assam, and Cinnamomum bejolghota (Hamilton) (Lauraceae) in Arunachal Pradesh, India. Puparia of A. theae are dimorphic, the females being larger than males. The puparia of the new genus differ from all other genera in having smaller ventral surface, submarginal wax secreting pores and dorsal submargin separated from the dorsal disc by a submarginal ridge. The diagnostic characteristics for puparia of the new genus are compared with closely related genera, Aleuroclava Singh, Aleuropleurocelus Drews & Sampson, Dialeuropora Quaintance & Baker, Tetralicia Harrison and Tetraleurodes Cockerell.
Spearcon Sequences for Monitoring Multiple Patients: Laboratory Investigation Comparing Two Auditory Display Designs
Authors: Li Simon Y. W. , Tse Man-Kei , Brecknell Birgit , Sanderson Penelope M.
Published: September 2018

Objective:

The aim was to compare the effectiveness of two auditory displays, implemented with spearcons (time-compressed speech), for monitoring multiple patients.

Background:

Sequences of sounds can convey information about patients’ vital signs, such as oxygen saturation (SpO2) and heart rate (HR). We tested whether participants could monitor five patients using spearcon-based sound sequences.

Method:

A 2 × 3 within-subjects design was used. The first factor was interface, with two levels: the ALL interface used spearcons to convey vital signs for all five patients, whereas the ABN (abnormal) interface represented patients who had normal vital signs with a low-pitched single-tone sound and patients who had at least one abnormal vital sign with spearcons. The second factor was the number of patients who had at least one abnormal vital sign: there were one, two, or three such patients in each monitoring sequence. Participants were 40 nonclinicians.

Results:

Participants identified abnormal patients’ SpO2 and HR levels and located abnormal patients in the sound sequence more accurately with the ABN interface than the ALL interface. Accuracy declined as the number of abnormal patients increased. Participants associated ABN with easier identification of vital signs, resulting in higher ratings of confidence and pleasantness compared with ALL.

Conclusion:

Sequences of spearcons may support effective eyes-free monitoring of multiple patients.

Application:

Sequences of spearcons may be useful in monitoring multiple patients and the underlying design principles may extend to monitoring in other domains such as industrial process control or control of multiple autonomous vehicles.
Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression
Authors: Zhou Yanling , Zheng Wei , Liu Weijian , Wang Chengyu , Zhan Yanni , Li Hanqiu , Chen Lijian , Li Mingding , Ning Yuping
Published: September 2018

Background:

Ketamine has proven to have rapid, robust antidepressant effects on treatment-resistant depression. However, whether repeated ketamine infusions would cause short-and long-term neurocognitive impairments was not clear. Our aims were to investigate the neurocognitive effects of six ketamine infusions and to examine the association between these infusions and the antidepressant response in patients with unipolar and bipolar depression.

Methods:

Six intravenous infusions of ketamine (0.5 mg/kg) over a 12-day period were administered to 84 patients with unipolar and bipolar depression. Severity of depressive symptoms and four domains of neurocognition, including speed of processing, working memory, visual learning and verbal learning, were assessed at baseline, one day following the last infusion and again two weeks post-infusion.

Results:

Significant improvements were found on speed of processing ( F=9.344, p<0.001) and verbal learning ( F=5.647, p=0.004) in a linear mixed model. The Sobel test showed significant indirect effects between time and improvement in speed of processing (Sobel test=3.573, p<0.001) as well as improvement in verbal learning (Sobel test=6.649, p<0.001), which were both significantly mediated by change in depressive symptoms. Logistic regression analysis showed ketamine responders had better visual learning at baseline than non-responders (B=0.118, p<0.001).

Conclusions:

Our findings suggest that neurocognitive function would not deteriorate after six ketamine infusions, while verbal learning and speed of processing improved over 13 days and 26 days of observation, respectively. However, this change was mainly accounted for by improvements in severity of depressive symptoms over time. Greater baseline visual learning predicted an antidepressant response over six ketamine infusions.
Enoxaparin 20 mg for thromboprophylaxis in severe renal impairment
Authors: Karaoui Lamis R. , Tawil Samah , Salameh Pascale , Chamoun Nibal
Published: September 2018

Objective

This study was performed to evaluate the efficacy of daily subcutaneous enoxaparin 20 mg in patients with renal failure.

Methods

This retrospective cohort study included nonsurgical patients aged ≥18 years with a creatinine clearance rate of <30 mL/minute who were prescribed enoxaparin 20 mg subcutaneously (SC) daily for ≥3 days. The main outcome measures were the occurrence of a venous thromboembolic event (VTE) and bleeding events.

Results

One hundred sixty patients were identified. VTE occurred in 9 patients (5.6%), and bleeding events occurred in 37 (23.1%). Multivariable analysis showed that an age of >75 years was significantly associated with an increased risk of bleeding, while a creatinine clearance rate of 15 to 29 mL/minute was significantly associated with a lower risk of bleeding.

Conclusion

In patients with renal failure, enoxaparin 20 mg SC daily resulted in a 5.6% incidence of VTE, which is similar to the previously published acceptable incidence of VTE in patients with normal renal function receiving enoxaparin 40 mg SC daily. The incidence of major bleeding events was 10%, which is lower than that previously published in the literature.
Creating Effective Urban Greenways and Stepping-stones: Four Critical Gaps in Habitat Connectivity Planning Research
Authors: Lynch Amy J.
Published: September 2018

Research in the field of ecology suggests that two main strategies, corridors and stepping-stones, can enhance urban habitat connectivity. While highly relevant to planning, no synthesis of this literature addresses planning research or implications. This review describes the effectiveness of corridor and stepping-stone strategies, actions that could enhance their ability to support animal movement, and the state of knowledge on connectivity planning, implementation, and outcomes. It concludes by identifying four significant gaps in our knowledge of planning for urban connectivity. Most critically, few studies assess the on-the-ground results of habitat connectivity planning and none examine the long-term outcomes.
Assessing delamination initiation of angle-ply laminates from fiber and matrix properties
Authors: Gu Jia-Jie , Huang Zheng-Ming
Published: September 2018

As a laminate is essentially bonded together from laminae by the matrix, any delamination of it must be initiated from a matrix failure. This article predicts the initiation of a laminate delamination through analyzing the matrix failure. A three-dimensional finite element approach is used to calculate the stress field of an angle-plied laminate under a uniaxial tension. The stresses in each lamina of the laminate are averaged with respect to the lamina thickness to eliminate a weak singularity near a free edge. Homogenized stresses in the matrix are then obtained through bridging model, which are further converted into true values by virtue of stress concentration factors of the matrix in the composite. Influence of any interface crack between the fiber and the matrix on the true stresses has been taken into account. A criterion for detecting the delamination initiation is proposed, which only involves the true stresses and the original strength data of the matrix. To assess the efficiency, comparisons between the predictions and available experiment data are made for a number of angle-plied laminates. Reasonable correlation has been found.
Standards for incontinence management products
Authors: Leander Håkan
Published: September 2018

This article focuses on international standards for incontinence management products. It describes what they are, how they are used, their limitations, and how they are developed. It outlines the standards currently available and those under development.
Dynamic reconfiguration of noniterative scientific applications: A case study with HPG aligner
Authors: Iserte Sergio , Martínez Héctor , Barrachina Sergio , Castillo Maribel , Mayo Rafael , Peña Antonio J
Published: September 2018

Several studies have proved the benefits of job malleability, that is, the capacity of an application to adapt its parallelism to a dynamically changing number of allocated processors. The most remarkable advantages of executing malleable jobs as part of a high performance computer workload are the throughput increase and the more efficient utilization of the underlying resources. Malleability has been mostly applied to iterative applications where all the processes execute the same operations over different sets of data and with a balanced per process load. Unfortunately, not all scientific applications adhere to this process-level malleable job structure. There are scientific applications which are either noniterative or present an irregular per process load distribution. Unlike many other reconfiguration tools, the Dynamic Management of Resources Application Programming Interface (DMR API) provides the necessary flexibility to make malleable these out-of-target applications. In this article, we study the particular case of using the DMR API to generate a malleable version of HPG aligner, a distributed-memory noniterative genomic sequencer featuring an irregular communication pattern among processes. Through this first conversion of an out-of-target application to a malleable job, we both illustrate how the DMR API may be used to convert this type of applications into malleable and test the benefits of this conversion in production clusters. Our experimental results reveal an important reduction of the malleable HPG aligner jobs completion time compared to the original HPG aligner version. Furthermore, HPG aligner malleable workloads achieve a greater throughput than their fixed counterparts.
Modified variational iteration method for analytical solutions of nonlinear oscillators
Authors: He Wei , Kong Hua , Qin Yan-Mei
Published: September 2018

The second-order nonlinear oscillators have rich dynamics. We proposed a novel analytical method based on both variational iteration method and Adomian method. The variational iteration method is used to establish an equivalent integral system. So then Adomian polynomials are adopted to linearize the strong nonlinear terms in nonlinear oscillators and analytical solutions are obtained successively.