bluuebunny/crossref_metadata_2025 huggingface dataset:
Extruded Preparations with Sour Cherry Pomace Influence Quality and Increase the Level of Bioactive Components in Gluten-Free Breads
Authors: Gumul Dorota , Korus Anna , Ziobro Rafał
Published: July 2020

Gluten-free bread (GFB) usually has a lower nutritional value than its traditional counterparts and is deficient in health-promoting substances. Therefore, GFB is often enriched in gluten-free components containing high levels of bioactive substances. In this work, an attempt has been made to enrich GFB with rice flour-based extruded preparations produced at 80 and 120°C with a share of 10 and 20% sour cherry pomace. The study material consisted of the abovementioned preparations together with breads produced with their 10% share. In order to prove that the extruded preparations could be the source of phenolic compounds, their level was determined. The influence of the applied additions was assessed taking into account nutritional composition (protein, fat, ash, and carbohydrates), level of the phenolic compounds (total phenolic content, flavonoids, anthocyanins, and phenolic acids), antioxidant potential, and physical properties of the breads (texture volume, color). It was shown that the extrudates with a share of fruit pomace cause an enrichment of gluten-free breads in bioactive compounds. The gluten-free breads enriched in extrudates with sour cherry pomace obtained at 120°C contained even 6 times more polyphenols than breads with extrudates obtained at 80°C. At the same time, these breads contained the highest levels of flavonoids and phenolic acids among all the analyzed samples. Bread with the addition of the extrudate produced with 20% fruit pomace at 120°C was the most favorable in terms of bioactive compounds (total phenolic content, flavonoids, anthocyanins, and phenolic acids) and antioxidative activity. The abovementioned bread showed the highest amount of total, soluble and insoluble fiber, and a significant amount of ash and sugars and revealed the lowest hardness during 3 days of storage, in comparison with the other samples.
The m6A Methylation-Regulated AFF4 Promotes Self-Renewal of Bladder Cancer Stem Cells
Authors: Gao Qian , Zheng Jin , Ni Zegui , Sun Pengli , Yang Congcong , Cheng Maosheng , Wu Mingqing , Zhang Xiuhong , Yuan Lin , Zhang Yingyin , Li Yang
Published: July 2020

The dynamic N6-methyladenosine (m6A) modification of mRNA plays a role in regulating gene expression and determining cell fate. However, the functions of m6A mRNA modification in bladder cancer stem cells (BCSCs) have not been described. Here, we show that global RNA m6A abundance and the expression of m6A-forming enzyme METTL3 are higher in BCSCs than those in non-CSCs of bladder cancer (BCa) cells. The depletion of theMETTL3inhibited the self-renewal of BCSCs, as evidenced by decreased ALDH activity and sphere-forming ability. Mechanistically, METTL3 regulates the m6A modification and thereby the expression of AF4/FMR2 family member 4 (AFF4), knockdown of which phenocopies theMETTL3ablation and diminishes the tumor-initiating capability of BCSCsin vivo. AFF4 binds to the promoter regions and sustains the transcription ofSOX2andMYCwhich have critical biological functions in BCSCs. Collectively, our results demonstrate the critical roles of m6A modification in self-renewal and tumorigenicity of BCSCs through a novel signaling axis of METTL3-AFF4-SOX2/MYC.
“Local versus Nonlocal” Enterprise Linkages of Global Cities: A Comparison between Beijing and Shanghai, China
Authors: Lu Jiayi , Sun Dongqi , Yu Jiali , Li Jiaming , Niu Fangqu
Published: July 2020

Two global cities of China, Beijing and Shanghai, have completely different development statuses with their hinterlands. There is a large economic development gap between Beijing and its hinterland, Hebei Province, while Shanghai has formed a highly integrated region with its hinterland, the Yangtze River Delta. According to the Outline of Collaborative Development of Beijing, Tianjin, and Hebei Province, enterprise linkages between Beijing and Hebei should be strengthened in order to narrow the economic gap between the center and the hinterland. On this basis, this paper proposes two hypotheses. (1) The economic gap between Beijing and Hebei has not really changed, because more enterprise linkages of Beijing are nonlocal. (2) The gradual narrowing of the economic gap between Shanghai and Jiangsu as well as Zhejiang is due to the fact that more enterprise linkages of Shanghai are local. We have used enterprise data on business registration from the State Administration for Industry and Commerce of China and have selected two indicators, namely, the number of headquarters-branches offices and the amount of enterprise investment, to examine the enterprise linkages between Beijing/Shanghai and their hinterlands as well as the hinterworld, and have verified these two hypotheses. The results show that nonlocal enterprise linkages based on the hinterworld are the main form in Beijing, while local enterprise linkages based on the hinterland are the main form in Shanghai. In addition, we have analyzed the mechanisms of formation of the enterprises linkages of the two cities and have put forward some policy suggestions.
A Multiscroll Chaotic Attractors with Arrangement of Saddle-Shapes and Its Field Programmable Gate Array (FPGA) Implementation
Authors: Wang Faqiang , Xiao Yufang
Published: July 2020

Based on the step function and signum function, a chaotic system which can generate multiscroll chaotic attractors with arrangement of saddle-shapes is proposed and the stability of its equilibrium points is analyzed. The under mechanism for the generation of multiscroll chaotic attractors and the reason for the arrangement of saddle shapes and being symmetric abouty-axis are presented, and the rule for controlling the number of scroll chaotic attractors with saddle shapes is designed. Based on the core chips including Altera Cyclone IV EP4CE10F17C8 Field Programmable Gate Array and Digital to Analog Converter chip AD9767, the peripheral circuit and the Verilog Hardware Description Language program for realization of the proposed multiscroll chaotic system is constructed and some experimental results are presented for confirmation. The research result shows that the occupation of multipliers and Phase-Locked Loops in Field Programmable Gate Array is zero.
Dietary and Circulating Fatty Acids and Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition
Authors: Yammine Sahar , Huybrechts Inge , Biessy Carine , Dossus Laure , Aglago Elom K. , Naudin Sabine , Ferrari Pietro , Weiderpass Elisabete , Tjønneland Anne , Hansen Louise , Overvad Kim , Mancini Francesca R. , Boutron-Ruault Marie-Christine , Kvaskoff Marina , Fortner Renée T. , Kaaks Rudolf , Schulze Matthias B. , Boeing Heiner , Trichopoulou Antonia , Karakatsani Anna , La Vecchia Carlo , Benetou Vassiliki , Masala Giovanna , Krogh Vittorio , Mattiello Amalia , Macciotta Alessandra , Gram Inger T. , Skeie Guri , Quirós Jose R. , Agudo Antonio , Sánchez Maria-José , Chirlaque Maria-Dolores , Ardanaz Eva , Gil Leire , Sartor Hanna , Drake Isabel , Idahl Annika , Lundin Eva , Aune Dagfinn , Ward Heather , Merritt Melissa A. , Allen Naomi E. , Gunter Marc J. , Chajès Véronique
Published: July 2020

Background:

Fatty acids impact obesity, estrogens, and inflammation, which are risk factors for ovarian cancer. Few epidemiologic studies have investigated the association of fatty acids with ovarian cancer.

Methods:

Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 1,486 incident ovarian cancer cases were identified. Cox proportional hazard models with adjustment for ovarian cancer risk factors were used to estimate HRs of ovarian cancer across quintiles of intake of fatty acids. False discovery rate was computed to control for multiple testing. Multivariable conditional logistic regression models were used to estimate ORs of ovarian cancer across tertiles of plasma fatty acids among 633 cases and two matched controls in a nested case–control analysis.

Results:

A positive association was found between ovarian cancer and intake of industrial trans elaidic acid [HR comparing fifth with first quintileQ5-Q1 = 1.29; 95% confidence interval (CI) = 1.03–1.62; Ptrend = 0.02, q-value = 0.06]. Dietary intakes of n-6 linoleic acid (HRQ5-Q1 = 1.10; 95% CI = 1.01–1.21; Ptrend = 0.03) and n-3 α-linolenic acid (HRQ5-Q1 = 1.18; 95% CI = 1.05–1.34; Ptrend = 0.007) from deep-frying fats were also positively associated with ovarian cancer. Suggestive associations were reported for circulating elaidic (OR comparing third with first tertileT3-T1 = 1.39; 95% CI = 0.99–1.94; Ptrend = 0.06) and α-linolenic acids (ORT3-T1 = 1.30; 95% CI = 0.98–1.72; Ptrend = 0.06).

Conclusions:

Our results suggest that higher intakes and circulating levels of industrial trans elaidic acid, and higher intakes of linoleic acid and α-linolenic acid from deep-frying fat, may be associated with greater risk of ovarian cancer.

Impact:

If causal, eliminating industrial trans-fatty acids could offer a straightforward public health action for reducing ovarian cancer risk.
Early Relapse Risk in Patients with Newly Diagnosed Multiple Myeloma Characterized by Next-generation Sequencing
Authors: D'Agostino Mattia , Zaccaria Gian Maria , Ziccheddu Bachisio , Rustad Even H. , Genuardi Elisa , Capra Andrea , Oliva Stefania , Auclair Daniel , Yesil Jennifer , Colucci Paola , Keats Jonathan J. , Gambella Manuela , Bringhen Sara , Larocca Alessandra , Boccadoro Mario , Bolli Niccolò , Maura Francesco , Gay Francesca
Published: July 2020

Purpose:

Duration of first remission is important for the survival of patients with multiple myeloma.

Experimental Design:

From the CoMMpass study (NCT01454297), 926 patients with newly diagnosed multiple myeloma, characterized by next-generation sequencing, were analyzed to evaluate those who experienced early progressive disease (PD; time to progression, TTP ≤18 months).

Results:

After a median follow-up of 39 months, early PD was detected in 191/926 (20.6%) patients, 228/926 (24.6%) patients had late PD (TTP >18 months), while 507/926 (54.8%) did not have PD at the current follow-up. Compared with patients with late PD, patients with early PD had a lower at least very good partial response rate (47% vs. 82%, P < 0.001) and more frequently acquired double refractoriness to immunomodulatory drugs (IMiD) and proteasome inhibitors (PI; 21% vs. 8%, P < 0.001). Patients with early PD were at higher risk of death compared with patients with late PD and no PD (HR, 3.65; 95% CI, 2.7–4.93; P < 0.001), showing a dismal median overall survival (32.8 months). In a multivariate logistic regression model, independent factors increasing the early PD risk were TP53 mutation (OR, 3.78, P < 0.001), high lactate dehydrogenase levels (OR, 3.15, P = 0.006), λ-chain translocation (OR, 2.25, P = 0.033), and IGLL5 mutation (OR, 2.15, P = 0.007). Carfilzomib-based induction (OR, 0.15, P = 0.014), autologous stem-cell transplantation (OR, 0.27, P < 0.001), and continuous therapy with PIs and IMiDs (OR, 0.34, P = 0.024) mitigated the risk of early PD.

Conclusions:

Early PD identifies a high-risk multiple myeloma population. Further research is needed to better identify baseline features predicting early PD and the optimal treatment approaches for patients at risk.
Toward a New Molecular Taxonomy of Diffuse Large B-cell Lymphoma
Authors: Ennishi Daisuke , Hsi Eric D. , Steidl Christian , Scott David W.
Published: July 2020

Diffuse large B-cell lymphoma (DLBCL) represents a grouping of clinically and biologically heterogeneous tumors. Application of advanced molecular technology has significantly expanded our knowledge of DLBCL pathobiology, allowing identification of subgroups with common, potentially targetable, biological themes. Here, we review the recent molecular analyses that could provide a paradigm shift to a new taxonomy, foundational to the rational transition to precision medicine. We discuss how classification systems may be synthesized into a common taxonomy, drawing strength from the relationships between genetic alterations, gene expression, and tumor microenvironment. Finally, challenges to translating such a taxonomy to the clinic will be outlined.
Salidroside Attenuates Hypoxia-Induced Expression of Connexin 43 in Corpus Cavernosum Smooth Muscle Cells
Authors: Zhao Jianfeng , Zhao Fan , Ye Miaoyong , Ma Ke , Huang Wenjie , Qian Le , Huang Xiaojun , Fu Huiyin , Lv Bodong
Published: July 2020

Introduction: Connexin 43 (Cx43) is the major component of gap junction in corpus cavernosum smooth muscle, which allows rapid intercellular communication. Cx43 coordinates corpus cavernosum smooth muscle cells and ensures erectile function. The role of hypoxia in Cx43 dysfunction resulting in erectile dysfunction has not been well studied, and salidroside has shown cell protective effects under hypoxia. Objective: We aimed to investigate the protective role of salidroside and the underlying mechanisms in hypoxia-induced dysfunction of Cx43. Methods: Corpus cavernosum smooth muscle cells prepared from young male Sprague-Dawley rats were pretreated with or without salidroside and exposed to hypoxic condition for 48 h. The cell viability, expression of hypoxia-inducible factor-1α (HIF-1α) and Cx43, and Ca2+ signals were investigated. Results: Pretreatment with salidroside attenuated loss of hypoxia-induced cell viability markedly and could downregulate the HIF-1α protein expression under hypoxia. Moreover, the expression of Cx43 was significantly increased by hypoxia but was decreased with salidroside pretreatment. The salidroside pretreated group exhibited enhanced release of intracellular Ca2+ in corpus cavernosum smooth muscle cells compared with the hypoxia group after stimulation. Conclusion: Salidroside has a protective effect against hypoxia-induced damage to corpus cavernosum smooth muscle cells.
A Case of Retroperitoneal Ganglioneuroma Accidentally Discovered by Laparoscopic Right Adrenalectomy
Authors: Nomura Shunsuke , Kawahara Takashi , Takeshima Tappei , Mitomi Takahiro , Takamoto Daiji , Sawazumi Tomoe , Inayama Yoshiaki , Uemura Hiroji
Published: July 2020

A 65-year-old man was referred to our hospital for his right adrenal adenoma. Adrenal vein blood sampling revealed primary hyperaldosteronism, and he was referred to our department for surgical resection of his right adenoma. During the operation, a small nodule was discovered in addition to the adrenal tumor. The pathological diagnosis of this nodule was ganglioneuroma. We herein report a rare case of ganglioneuroma incidentally discovered by laparoscopic right adrenalectomy.
Predictors of Contrast Volume in Transcatheter Aortic Valve Replacement
Authors: Goldsweig Andrew M. , Lyden Elizabeth , Aronow Herbert D. , Kolte Dhaval , Pavlides Gregory , Barton David , Chatzizisis Yiannis  , Gumina Richard J. , Abbott J. Dawn
Published: July 2020

Background: Contrast-induced acute kidney injury (CIAKI) is a frequent and serious complication of transcatheter aortic valve replacement (TAVR). The most important procedural risk factor for CIAKI is contrast volume. Objectives: Because contrast volume is a modifiable factor that directly predicts CIAKI, we sought to identify predictors of increased contrast volume in TAVR patients. Identification of such predictors may allow both prediction and mitigation of CIAKI risk following TAVR. Method: We retrospectively analyzed data from consecutive patients not on hemodialysis who underwent successful TAVR at a single US center from 2013 to 2018. Using multivariable linear regression modelling, we assessed the relationships between contrast volumes and 49 patient and procedural factors hypothesized to be potential predictors. Results: In 295 patients, we identified 17 factors that independently predicted contrast volume, 10 of which contributed 90% of the complete model’s r2 value. Procedure year (suggesting a learning curve), aortic insufficiency, radiation dose, prior AVR, and previous pacemaker placement were statistically the most significant predictors of CIAKI. TAVR device and diabetes were notably not predictors. Conclusions: To predict and reduce contrast use in TAVR, patients at risk for increased contrast volume may be identified using the predictors elucidated in this study. For such patients, strategies for contrast reduction and renal protection may be employed.
A Combination of Hemodialysis with Hemoperfusion Helped to Reduce the Cardiovascular-Related Mortality Rate after a 3-Year Follow-Up: A Pilot Study in Vietnam
Authors: Nguyen Huu Dung , Dao Bui Quy Quyen , Nguyen Thi Thu Hai , Phan The Cuong , Nguyen Thi Hong Quyen , Nguyen Duc Loc , Do Quyet , Le Viet Thang
Published: July 2020

Aims: Moderate to severe hyperparathyroidism (parathyroid hormone [PTH] concentrations ≥600 pg/mL) may increase the risk of cardiovascular problems and bone disease. We assume that a combination of hemodialysis with hemoperfusion may reduce the cardiovascular-related mortality rate in maintenance hemodialysis. Subjects and Methods: From 625 maintenance hemodialysis patients, 93 people met with our inclusion criteria. Based on the level of serum PTH, the patients were divided into 2 groups: 46 patients who underwent a combination of hemodialysis and hemoperfusion (HD + HP group) for consecutive 3 years and 47 patients who used hemodialysis only (HD group). Results: During 3 years of follow-up, the ratio of mortality was 4.3% in the HD + HP group which was significantly lower than in the HD group (17%), p = 0.049. Based on Kaplan-Meier analysis of cardiovascular-related mortality, patients in the HD group (red line) exhibited a significantly higher death rate compared to the HD + HP group (violet line) (log-rank test, p = 0.049). Conclusion: We demonstrated that a combination of hemodialysis and hemoperfusion for 3 years helped to reduce the cardiovascular-related mortality rate.
Characteristics of Patients with an Abnormally Decreased Plasma Xanthine Oxidoreductase Activity in Acute Heart Failure Who Visited the Emergency Department
Authors: Shirakabe Akihiro , Okazaki Hirotake , Matsushita Masato , Shibata Yusaku , Goda Hiroki , Shigihara Shota , Asano Kazuhiro , Tani Kennichi , Kiuchi Kazutaka , Murase Takayo , Nakamura Takashi , Kobayashi Nobuaki , Hata Noritake , Asai Kuniya , Shimizu Wataru
Published: July 2020

Background: The factors associated with a low plasma xanthine oxidoreductase (XOR) activity were not elucidated in patients with acute heart failure (AHF). Methods: Two-hundred and twenty-nine AHF patients who visited the emergency department were prospectively analyzed. AHF patients were divided into 3 groups according to the plasma XOR quartiles (Q1 = low-XOR group [n = 57], Q2/Q3 = middle-XOR group [n = 115], and Q4 = high-XOR group [n = 57]). The prognostic nutritional index (PNI) and the controlling nutritional status (CONUT) score were evaluated. Results: The multivariate logistic regression model showed that the nutritional status (PNI: OR 1.044, 95% CI 1.000–1.088; CONUT: OR 3.805, 95% CI 1.158–12.498), age, and serum creatinine level were independently associated with a low plasma XOR activity. The Kaplan-Meier curve showed a significantly lower incidence of heart failure events in the low-XOR group than in the middle + high-XOR group (hazard ratio, HR 1.648, 95% CI 1.061–2.559). In particular, a low XOR activity with an increased serum creatinine level (>1.21 mg/dL) was independently associated with heart failure events (HR 1.937, 95% CI 1.199–3.130). Conclusion: A low plasma XOR activity was associated with malnutrition, renal dysfunction, and aging in AHF. A low XOR activity complicated with renal dysfunction leads to adverse long-term outcomes.
Renal Allograft Compartment Syndrome: A Case Report and Review of the Literature
Authors: El-Bandar Nasrin , Lerchbaumer Markus , Hubatsch Mandy , Lichy Isabel Michaela , Schulz Matthias R.G. , Friedersdorff Frank
Published: July 2020

Kidney transplantation is the treatment of choice for patients with ESRD. One rare complication after transplantation is the development of renal allograft compartment syndrome (RACS). We present a case of 1 patient who developed RACS due to compression of the transplant vein, which was then treated by salvaging the kidney transplant using urgent decompression surgery with mesh fascial closure. We postulate that this technique is safe and should be the treatment of choice for patients with RACS.
Intravenous Thrombolysis Is Not Associated with Increased Time to Endovascular Treatment
Authors: Hinsenveld Wouter H. , de Ridder Inger R. , van Oostenbrugge Robert J. , van Zwam Wim H. , Vos Jan Albert , Coutinho Jonathan M. , Lycklama à Nijeholt Geert J. , Boiten Jelis , Schonewille Wouter J. ,   MR CLEAN Registry Investigators
Published: July 2020

Background: Endovascular treatment (EVT) with or without intravenous thrombolysis (IVT) is effective and safe in is­chemic stroke caused by large vessel occlusion, but IVT might delay time to EVT or increase risk of intracranial hemorrhage (ICH). We assessed the influence of prior IVT on time to treatment and risk of ICH in patients treated with EVT. Methods: We analyzed data from the MR CLEAN Registry and included patients with an anterior circulation occlusion treated with EVT who presented directly to an intervention center, between 2014 and 2017. Primary endpoint was the door to groin time. Secondary outcomes were workflow time intervals and safety outcomes. We compared patients who received EVT only with patients who received IVT prior to EVT. Results: We included 1,427 patients directly referred to an intervention center of whom 1,023 (72%) received IVT + EVT. Adjusted door to CT imaging and door to groin time were shorter in IVT + EVT patients (difference 5.7 min [95% CI: 4.6–6.8] and 7.0 min [95% CI: 2.4–12], respectively) while CT imaging to groin time was similar between the groups. Early recanalization on digital subtraction angiography before EVT was seen more often after prior IVT (11 vs. 5.2%, aOR 2.4 [95% CI: 1.4–4.2]). Rates of symptomatic ICH were similar. Conclusion: Prior IVT did not delay door to groin times and was associated with higher rates of early recanalization, without increasing the risk of ICH. Our results do not warrant withholding IVT prior to EVT.
Intravenous Thrombolysis Guided by Perfusion CT with Alteplase in >4.5 Hours from Stroke Onset
Authors: Medina-Rodriguez Manuel , Millan-Vazquez Manuel , Zapata-Arriaza Elena , Escudero Irene , Pardo-Galiana Blanca , Cabezas-Rodriguez Juan Antonio , Lebrato-Hernandez Lucia , Ortega-Quintanilla Joaquin , de Albóniga-Chindurza Asier , Ocete-Perez Rafael Felix , Jurado-Serrano Juan , Gonzalez-Garcia Alejandro , Cayuela Aurelio , Moniche Francisco
Published: July 2020

Introduction: The benefit of intravenous thrombolysis (IVT) in wake-up stroke (WUS), stroke of unknown time of onset (SUKO), or when time exceeds 4.5 h from last-seen-normal (LSN) guided by CT perfusion (CTP) or MRI has been recently suggested. However, there is limited information of IVT in those patients in real-world studies. Objective: Our aim was to evaluate safety and efficacy of IVT selected by CTP in patients with WUS, SUKO, or stroke of time onset beyond 4.5 h. Material and Methods: We studied a prospective cohort of patients who underwent IVT from January 2010 to December 2017. Two groups were defined: standard of care group (SC) included patients with time onset <4.5 h and CTP group included patients with WUS, SUKO, or onset beyond >4.5 h from LSN with penumbra area in CTP. We evaluated baseline characteristics, functional outcomes according to modified Rankin Scale (mRS) at discharge and at 90 days, and intracranial hemorrhages rates. Results: 657 patients were studied: 604 (92%) were treated in the SC group and 53 (8%) in the CTP group. The mean NIHSS score was 9.8 in the CTP group versus 13 in the SC group (p = 0.001). Seventeen patients in the CTP group (32.1%) received bridging therapy with mechanical thrombectomy (MT). Last time seen well-to-needle time was 538 versus 155 min (p < 0.001). The incidence of symptomatic intracranial hemorrhage was equal in both groups (3.8 vs. 3.8%, p = 1). Good functional outcome (mRS < 2) was achieved in both groups (72 vs. 60.4%, p = 0.107). Conclusions: IVT in patients with WUS, SUKO, or stroke beyond >4.5 h from LSN, with salvageable brain tissue on CTP, seems to be safe and has similar functional outcomes at 90 days to the standard therapeutic window, even when combined with MT.
Sensitivity and Specificity of the NETest: A Validation Study
Authors: Al-Toubah Taymeyah , Cives Mauro , Valone Tiffany , Blue Kirsten , Strosberg Jonathan
Published: July 2020

Background: Secretory tumor markers traditionally measured in patients with neuroendocrine tumors (NET) are lacking sensitivity and specificity, and consequently they are of limited clinical utility. The NETest, a novel blood multigene RNA transcript assay, has been found to be highly sensitive and specific. We sought to validate the sensitivity of the NETest in a population of metastatic well-differentiated NETs of gastroenteropancreatic and lung origin and to evaluate NETest specificity in a mixed population of metastatic non-NET gastrointestinal (GI) malignancies and healthy individuals. Design and Methods: Forty-nine patients with metastatic NETs, 21 patients with other metastatic GI cancers, and 26 healthy individuals were enrolled in the study. Samples were sent in a blinded fashion to a central laboratory, and an NETest value of 0–13% was considered normal. Results: Using 13% as the upper limit of normal, the sensitivity of the NETest was 98% (95% CI 89–100%). The overall specificity was 66% (95% CI 51–79%), with 16 false-positive results. Specificity was 81% (95% CI 62–92%) among 26 healthy individuals and 48% (95% CI 26–70%) among patients with other GI malignancies. Using an updated normal range of 0–20%, sensitivity was unchanged, but specificity improved to 100% among healthy participants and to 67% among patients with other cancers. Conclusions: The sensitivity of the NETest is exceptionally high (>95%) in a population of metastatic, well-differentiated NETs. Specificity within a healthy population of patients is exceptionally high when using a normal range of 0–20% but relatively low when evaluating patients with other GI malignancies.
Regression of Atherosclerosis in ApoE−/− Mice Via Modulation of Monocyte Recruitment and Phenotype, Induced by Weekly Dosing of a Novel “Cytotopic” Anti‐Thrombin Without Prolonged Anticoagulation
Authors: Chen Daxin , Li Ke , Festenstein Sam , Karegli Julieta , Wilkinson Hannah , Leonard Hugh , Wei Lin‐Lin , Ma Ning , Xia Min , Tam Henry , Wang Jian‐an , Xu Qingbo , McVey John H. , Smith Richard A. G. , Dorling Anthony
Published: July 2020

Background

Anticoagulants induce atherosclerosis regression in animal models but exploiting this clinically is limited by bleeding events. Here we test a novel thrombin inhibitor,
PTL
060, comprising hirulog covalently linked to a synthetic myristoyl electrostatic switch to tether to cell membranes.

Methods and Results

ApoE−/− mice were fed chow or high‐fat diets, before transplantation of congenic aortic segments or injection of
PTL
060, parental hirulog, control saline, or labeled
CD
11b positive cells. Aortic transplants from transgenic mice expressing anticoagulants on endothelium did not develop atherosclerosis. A single intravenous injection of
PTL
060, but not hirulog inhibited atheroma development by >50% compared with controls when assessed 4 weeks later. Mice had prolonged bleeding times for only one seventh of the time that
PTL
060 was biologically active. Repeated weekly injections of
PTL
060 but not hirulog caused regression of atheroma. We dissected 2 contributory mechanisms. First, the majority of CCR2+ (C‐C chemokine receptor type 2+) monocytes recruited into plaques expressed CCR7 (C‐C chemokine receptor type 7), ABCA1 (ATP‐binding cassette transporter – 1), and interleukin‐10 in
PTL
060 mice, a phenotype seen in <20% of CCR2+ recruits in controls. Second, after several doses, there was a significant reduction in monocyte recruits, the majority of which were CCR2‐negative with a similar regression‐associated phenotype. Regression equivalent to that induced by intravenous
PTL
060 was induced by adoptive transfer of
CD
11b+ cells pre‐coated with
PTL
060.

Conclusions

Covalent linkage of a myristoyl electrostatic switch onto hirulog in
PTL
060 uncouples the pharmacodynamic effects on hemostasis and atherosclerosis, such that plaque regression, mediated predominantly via effects on monocytes, is accompanied by only transient anticoagulation.
A revision of the genus Orchestia Leach, 1814 with the reinstatement of O. inaequalipes (K.H. Barnard, 1951), the designation of a neotype for Orchestia gammarellus (Pallas, 1776) and the description of three new species (Crustacea: Amphipoda: Talitridae: Talitrinae)
Authors: MYERS ALAN A. , LOWRY JAMES K.
Published: July 2020

The amphipod genus Orchestia is revised. It now includes 10 species of which three are new: O. forchuensis sp. nov. from north-eastern North America and Iceland., O. perezi sp. nov. from Chile and O. tabladoi sp. nov. from Argentina. Orchestia inaequalipes (K.H. Barnard 1951) is reinstated. The type species of the genus, O. gammarellus is redescribed based on material from Fountainstown, Ireland and a neotype is established to stabilize the species. The species was originally described from a garden in Leiden, far from the sea. Its true identity is unknown and no type material exists. Orchestia gammarellus (Pallas, 1776) is shown to be a sibling species group with members in both hemispheres of the temperate Atlantic as well along the Pacific coast of South America. A hypothesis for the establishment of the current distribution of Orchestia species is presented that extends back to the Cretaceous.
Type designations for fireflies (Coleoptera: Lampyridae) of the Biologia Centrali Americana Gorham, 1881 housed in the Natural History Museum, London
Authors: MARTIN GAVIN J. , POWELL GARETH S.
Published: July 2020

The Biologia Centrali Americana (B.C.A.) is comprised of eight volumes that deal specifically with Coleoptera. These volumes were split into 18 parts and were published between 1879 and 1911. The family Lampyridae was treated in two parts, the main text (1881) with a supplement (1884). Within volume three, part 2, Gorham lists ~90 species in 14 genera, not including the Phengodini subfamily. Of these, Gorham provided original descriptions for 37 species. During recent research visits (2018 and 2020) the authors were able to study material pertinent to the B.C.A. We were able to confidently designate holotypes, lectotypes, and paralectotypes following ICZN articles 73.1 and 74.1 within these species. Two species described by Gorham (1881) are not treated here. Phaenolis nirgricollis was located with a single specimen, already designate as the holotype. Two female syntypes of Photinus consanguineous were located, however Oliver (1907) synonymized these females with Photinus pyralis. These designations contribute to a larger taxonomic effort to stabilize the nomenclature of this group. The species described in the supplement will be treated in a future work. Subfamilies are listed according to Martin et al. (2019) and genera/species within each subfamily are listed according to the order in Gorham (1881).
Oxynoemacheilus cilicicus, a new nemacheilid loach from the Göksu River in southern Anatolia (Teleostei: Nemacheilidae)
Authors: KAYA CÜNEYT , TURAN DAVUT , BAYÇELEBİ ESRA , KALAYCI GÖKHAN , FREYHOF JÖRG
Published: July 2020

Oxynoemacheilus cilicicus, new species, is described from the Göksu, Seyhan and Ceyhan rivers in southern Turkey. It is distinguished from other Oxynoemacheilus species in the Eastern Mediterranean Sea basin by possession of an incomplete lateral line, terminating before the vertical of the dorsal-fin origin or slightly behind the dorsal-fin base, a deeply emarginate caudal fin, no suborbital groove in male individuals, and a series of dark-brown bars on the flank not interrupted along the lateral line. Molecular data suggest that Oxynoemacheilus cilicicus is characterised by 22 variable nucleotide substitutions and a minimum K2P distance of 4.09% with O. panthera in the mtDNA COI barcode region.
Redescription of three species of Apobaetis Day, 1955 (Ephemeroptera: Baetidae)
Authors: CRUZ PAULO VILELA
Published: July 2020

The genus Apobaetis Day is one of the few lineages of the family Baetidae distributed throughout the continental Americas. Three very similar species of this genus—Apobaetis etowah (Traver), Apobaetis signifer Lugo-Ortiz & McCaffety, and Apobaetis fiuzai Salles & Lugo-Ortiz—have important morphological details, pertinent to species identification, that remain to be described. This lack of detailed taxonomic information has resulted in ample misdiagnoses of the species, particularly regarding A. fiuzai in South America. In fact, almost all the recently collected specimens have been assigned to this species. The present study aimed to establish a new morphological diagnosis of these three Apobaetis species through a redescription of their larvae, based on type material, and the proposition of a new identification key for larvae of this genus. The review of the type specimens supports two conclusions: (i) that A. etowah, A. signifer, and A. fiuzai are highly similar, yet can be considered as distinct species, and (ii) the previous diagnoses and keys do not effectively separate A. fiuzai from A. signifer.
Taxonomic study of the leafhopper genus Singapora (Hemiptera: Cicadellidae: Typhlocybinae: Erythroneurini) from China with a new species
Authors: LIN SHUANGHU , ZHANG YALIN
Published: July 2020

The genus Singapora Mahmood is reviewed with one new species from China, Singapora shiqianensis sp. nov.. Detailed morphological description, illustration of this new species and a key to all known species (males) from China are provided.
Hybrid tourist information search German tourists' combination of digital and analogue information channels
Authors: Zillinger Malin
Published: July 2020

In a rapidly digitalizing world, both tourism actors and researchers are striving to keep pace with developments in tourist information search. This is not an easy task, as research results are pointing at different directions. Moreover, while tourism research is indicating the importance of analogue and digital information sources in parallel, tourism actors focus mainly on digital development. This does not make sense. This study aims to contribute to the academic debate on the importance and combination of information channels. The paper is based on a multi-method approach including surveys and interviews. Results show that tourists are hybrid information searchers who are loyal to their information channels and who dismiss too much of information. Empirically, the study is based on German tourists in Sweden.
The M1 muscarinic acetylcholine receptor in the crypt stem cell compartment mediates intestinal mucosal growth
Authors: Greig Chasen J , Armenia Sarah J , Cowles Robert A
Published: July 2020

Maintenance of the highly plastic intestinal epithelium relies upon stem cells localized to intestinal crypts. Recent evidence suggests muscarinic acetylcholine signaling impacts epithelial barrier function, proliferation, and apoptosis. We hypothesized that the intestinal crypt base would express specific muscarinic acetylcholine receptors that drive proliferation in this critical region. Intestinal segments spanning the small bowel were procured from wild-type C57Bl/6 mice to determine muscarinic acetylcholine receptor mRNA expression and create sections on laser capture microdissection slides for analysis of crypt base cells. RT-PCR was performed using primers targeting the five muscarinic acetylcholine receptor subtypes (M1–M5), LGR5, BIII-tubulin, and GAPDH. To determine the effects of muscarinic agonism in vivo, osmotic pumps delivering the M1 muscarinic acetylcholine receptor agonist McN-A-343 were implanted into wild type mice for one week. Segments were harvested, histologic sections created, and morphometric and proliferative parameters measured. In full-thickness intestinal samples, muscarinic acetylcholine receptor subtypes M1–M4 were found in all regions, while M5 was localized to the proximal jejunum. In crypt-base cells, the M1 muscarinic acetylcholine receptor subtype was the only subtype found and was present in all regions. LGR5 was present in all laser capture microdissection samples, indicating the capture of intestinal stem cells. In vivo experiments conducted with McN-A-343 revealed significantly increased villus height, crypt depth, and crypt-cell proliferation. The presence of M1 muscarinic acetylcholine receptor mRNA within the stem cell niche in the intestinal crypt base coupled with increased mucosal growth with M1 receptor stimulation in vivo suggests that the cholinergic system, via the M1 muscarinic acetylcholine receptor, is a critical mediator of intestinal mucosal homeostasis.

Impact statement

Localization of a specific subtype of the muscarinic acetylcholine receptor in the crypt stem cell compartment suggests a critical role in intestinal mucosal homeostasis. Here we demonstrate the localization of the M1 muscarinic acetylcholine receptor to the stem cell compartment and demonstrate increase morphometric and proliferative parameters when this is stimulated in vivo. These data provide novel information about this complex signaling microenvironment and offer potential future therapeutic targets for future study.
Are Couples More Satisfied When They Match in Sexual Desire? New Insights From Response Surface Analyses
Authors: Kim James J. , Muise Amy , Barranti Max , Mark Kristen P. , Rosen Natalie O. , Harasymchuk Cheryl , Impett Emily
Published: July 2020

While sexual frequency and satisfaction are strong contributors to the quality and longevity of romantic relationships and overall well-being, mismatches in sexual desire between partners are common and have been linked with poorer satisfaction. Previous findings linking mismatches in desire with poorer relationship and sexual outcomes have typically been derived using difference scores, an approach that does not account for partners’ overall levels of desire. In a sample of 366 couples, we investigated whether partners who match in desire are more satisfied than desire-discrepant couples. Results of dyadic response surface analyses provided no support for a unique matching effect. Higher desire rather than matching in desire between partners predicted relationship and sexual satisfaction. These findings shed new light on whether the correspondence between partners’ levels of sexual desire is associated with satisfaction and suggest the need to focus on sustaining desire and successfully navigating differences rather than promoting matching in desire.
Synthesis of Various Size Gold Nanoparticles by Chemical Reduction Method with Different Solvent Polarity
Authors: Hussain Mohamed Hasaan , Abu Bakar Noor Fitrah , Mustapa Ana Najwa , Low Kim-Fatt , Othman Nur Hidayati , Adam Fatmawati
Published: July 2020

Complicated and strict protocols are followed to tune the size of gold nanoparticles (GNPs) in chemical synthesis methods. In this study, we address the polarity of solvents as a tool for tailoring the size of GNPs in the chemical reduction method. The effects of varying polarity index of the reaction medium on synthesizing gold nanoparticles by chemical reduction method have been investigated. Ethanol as a polar solvent, ethanol–water mixture as reaction medium, L-ascorbic acid as reducing agent, and polyvinylpyrrolidone as stabilizer were used to synthesize GNPs. The polarity index of the reaction medium was adjusted by changing the volume ratio of ethanol to water. UV–Vis, dynamic light scattering (DLS), and transmission electron microscopy (TEM) characterizations reveal that the growth of nanoparticles was gradually increased (~ 22 to 219 nm hydrodynamic diameter) with decreasing value of polarity index of the reaction medium (~ 8.2 to 5.2). Furthermore, the high polarity index of the reaction medium produced smaller and spherical nanoparticles, whereas lower polarity index of reaction medium results in bigger size of GNPs with different shapes. These results imply that the mechanistic of the growth, assembly, and aggregation phenomena of ligand or stabilizer-capped GNPs strongly rely on the polarity of solvent molecules. Using the proposed methodology, wide size range of GNPs with different morphology sizes can be synthesized by simply modulating the volume percentage of organic solvent in the reaction medium.
Modified paramedian versus conventional paramedian technique in the residency training: an observational study
Authors: Chen Shih-Hong , Chen Shiou-Sheng , Lai Chao-Lun , Su Fang-Ying , Tzeng I-Shiang , Chen Li-Kuei
Published: July 2020

Background

Residency training includes positive and negative aspects. Well-trained doctors must be educated, but the process may bring additional risks to patients. Anesthesiologists’ performance when conducting neuraxial anesthesia is related to their experience. We hypothesized that a modified neuraxial anesthesia method would improve both residency training and patient safety.

Methods

We recruited 518 patients who were scheduled for a cesarean section and used spinal anesthesia (n = 256), epidural anesthesia (n = 154), and combined spinal–epidural anesthesia (SEA;n = 108). We observed and evaluated the anesthesia performance of five second-year resident anesthesiologists in elective cesarean sections using the conventional and modified methods. The number of attempts, implant error rate, and the incidence of complications were recorded and analyzed.

Results

Better success puncture attempts occurred in all three groups when the modified method was applied. For the groups with an implant assessment, the complication rate and implant error rate were lower when using the modified method. We employed generalized estimating equation (GEE) analysis to correct for possible confounding factors. When using the conventional method, the resident anesthesiologists required more attempts, made more implant errors, and caused more complications in patients.

Conclusions

We found that a modified method for neuraxial anesthesia could improve residency performance and patient safety. The modified method may be a suitable training process for resident anesthesiologists when practicing neuraxial anesthesia.

Trial registration

The study was approved by the Research Ethics Committee of National Taiwan University (IRB:200812040R) Clinicaltrials register:NCT03389672.
Haemato-immunological responses and effectiveness of feed-based bivalent vaccine against Streptococcus iniae and Aeromonas hydrophila infections in hybrid red tilapia (Oreochromis mossambicus × O. niloticus)
Authors: Monir Md Shirajum , Yusoff Sabri bin Mohd , Zulperi Zarirah binti Mohamed , Hassim Hasliza binti Abu , Mohamad Aslah , Ngoo Muhamad Sofie bin Mohd Hafiz , Ina-Salwany Md Yasin
Published: July 2020

Background

Streptococcosis and Motile Aeromonad Septicemia (MAS) are important diseases of tilapia,Oreochromisspp. and causes huge economic losses in aquaculture globally. The feed-based vaccination may be an alternative to minimize major infectious diseases in tilapia. Thus, this study aims to evaluate the haemato-immunological responses and effectiveness of a newly developed feed-based killed bivalent vaccine againstStreptococcus iniaeandAeromonas hydrophilain hybrid red tilapia. A total of 495 hybrid red tilapia of 61.23 ± 4.95 g were distributed into 5 groups (each with triplicate). The fish were immunized orally through bivalent (combinedS. iniaeandA. hydrophila) spray vaccine (BS group), bivalent formulate vaccine (BF group), monovalentS. iniaevaccine (MS group), monovalentA. hydrophilavaccine (MA group) and unvaccinated as a control group. The vaccine was orally administered on days 0, 14 and 42 applied feed-based bacterin at 5% body weight. The blood and spleen samples were collected from all groups on 7, 21 and 49 days post-vaccination, and also 96 h post-infection to assess their haemato-immune responses.

Results

Compared with the unvaccinated group, leukocyte, lymphocytes, monocytes, granulocytes counts in vaccinated groups were significantly (P < 0.05) increased on 21, 49 days post-vaccination and also 96 h post-infection, while erythrocytes, haemoglobin and haematocrit in vaccinated groups were significantly (P < 0.05) enhanced only 96 h post-infection. Additionally, the lysozyme and phagocytic activity and, serum antibody (IgM) were significantly higher (P < 0.05) againstS. iniaeandA. hydrophilain vaccinated groups compared to the unvaccinated group in the pre- and post-infection. Results from the challenge through co-infection withS. iniaeandA. hydrophilashowed the relative percent survival (RPS) in BF group was 76.67 ± 4.71%, which had the capacity to induce significant protection (P < 0.05) compared to others groups.

Conclusions

This study demonstrates the bivalent formulate (BF) group could elicit significant non-specific and specific immunological responses with higher protection in hybrid red tilapia. In addition, this newly developed feed-based bivalent vaccination can be a promising technique for effective and large scale fish immunization in the aquaculture industry.
Development of a computer-based quantification method for immunohistochemically-stained tissues and its application to study mast cells in equine wound healing (proof of concept)
Authors: Dubuc Valérie , Laverty Sheila , Richard Hélène , Doré Monique , Theoret Christine
Published: July 2020

Background

There is a growing interest in the scientific community to use computer-based software programs for the quantification of cells during physiological and pathophysiological processes. Drawbacks of computer-based methods currently used to quantify immunohistochemical staining are the complexity of use, expense of software and overly-simplified descriptions of protocol thereby limiting reproducibility. The precise role of mast cells in equine cutaneous wound healing is unknown. Given the contribution of mast cells to the chronic inflammation observed in human keloid, a pathology similar to exuberant granulation tissue (EGT) in horses, mast cells might be present in high numbers in equine limb wounds predisposed to EGT. The main goal of this study was to develop a reliable and reproducible quantification method for immunostained tissues using a computer software that is widely available, at no cost, to the scientific community. A secondary goal was to conduct a proof of concept using the newly-established method to quantify mast cells during wound healing at different anatomical sites (body and limb) in horses to see if a different pattern is observed in limb wounds, which are predisposed to EGT.

Results

A good intraclass correlation coefficient (ICC, 0.67p < 0.05) was found between the computer-based ImageJ method and manual counting. An excellent intra-operator ICC of 0.90 (p < 0.01) was found for the ImageJ quantification method while a good interoperator ICC of 0.69 (p < 0.01) was measured. No significant difference was observed between the variation of the ImageJ and that of the manual counting method. Mast cells were localized below the epidermis, around cutaneous appendages and blood vessels. Mast cell numbers did not differ significantly in relation to anatomical location or time of healing.

Conclusions

The computer-based quantification method developed is reliable, reproducible, available, cost-free and could be used to study different physiological and pathological processes using immunohistochemistry.