bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid broadband ground motion simulation validation of small magnitude earthquakes in Canterbury, New Zealand
Authors: Lee Robin L , Bradley Brendon A , Stafford Peter J , Graves Robert W , Rodriguez-Marek Adrian
Published: February 2020

Ground motion simulation validation is an important and necessary task toward establishing the efficacy of physics-based ground motion simulations for seismic hazard analysis and earthquake engineering applications. This article presents a comprehensive validation of the commonly used Graves and Pitarka hybrid broadband ground motion simulation methodology with a recently developed three-dimensional (3D) Canterbury Velocity Model. This is done through simulation of 148 small magnitude earthquake events in the Canterbury, New Zealand, region in order to supplement prior validation efforts directed at several larger magnitude events. Recent empirical ground motion models are also considered to benchmark the simulation predictive capability, which is examined by partitioning the prediction residuals into the various components of ground motion variability. Biases identified in source, path, and site components suggest that improvements to the predictive capabilities of the simulation methodology can be made by using a longer high-frequency path duration model, reducing empirical V s30-based low-frequency site amplification, and utilizing site-specific velocity models in the high-frequency simulations.
Correlations of spectral accelerations in the Chilean subduction zone
Authors: Candia Gabriel , Poulos Alan , de la Llera Juan Carlos , Crempien Jorge G.F. , Macedo Jorge
Published: February 2020

The correlation between spectral accelerations is key in the construction of conditional mean spectra, the computation of vector-valued seismic hazard, and the assessment of seismic risk of spatially distributed systems, among other applications. Spectral correlations are highly dependent on the earthquake database used, and thus, region-specific correlation models have been developed mainly for earthquakes in western United States, Europe, Middle East, and Japan. Correlation models based on global data sets for crustal and subduction zones have also become available, but there is no consensus about their applicability on a specific region. This study proposes a new correlation model for 5% damped spectral accelerations and peak ground velocity in the Chilean subduction zone. The correlations obtained were generally higher than those observed from shallow crustal earthquakes and subduction zones such as Japan and Taiwan. The study provides two illustrative applications of the correlation model: (1) computation of conditional spectra for a firm soil site located in Santiago, Chile and (2) computation of bivariate hazard for spectral accelerations at two structural periods.
Loncastuximab tesirine, an anti-CD19 antibody-drug conjugate, in relapsed/refractory B-cell acute lymphoblastic leukemia
Authors: Jain Nitin , Stock Wendy , Zeidan Amer , Atallah Ehab , McCloskey James , Heffner Leonard , Tomlinson Benjamin , Bhatnagar Bhavana , Feingold Jay , Ungar David , Chao Grace , Zhang Xiaoyan , Qin Yajuan , Havenith Karin , Kantarjian Hagop , Wieduwilt Matthew J.
Published: February 2020

Relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) remains a therapeutic challenge. Loncastuximab tesirine is an antibody-drug conjugate against CD19, an antigen expressed in many B-cell malignancies. This open-label, single-arm, dose-escalation, dose-expansion study assessed the safety, tolerability, pharmacokinetics (PKs), immunogenicity, and preliminary clinical activity of loncastuximab tesirine in adults with R/R B-ALL. A total of 35 patients were enrolled, with a median age of 55 years (range, 20-80) and a median of 3 prior therapies (range, 1-15). All patients received at least 1 IV infusion of loncastuximab tesirine at 15 to 150 μg/kg once every 3 weeks (Q3W; n = 30) or 50 μg/kg IV weekly (n = 5). Common treatment-emergent adverse events (TEAEs) were nausea (42.9%), febrile neutropenia (37.1%), and reversible liver test abnormalities. Grade ≥3 TEAEs were reported in 85.7% patients, most commonly febrile neutropenia and other hematologic abnormalities and reversible liver test abnormalities. There were no treatment-related deaths. Four patients (11.4%) had grade 2 infusion-related reactions, and 1 patient (150 μg/kg Q3W) had a dose-limiting toxicity of hyperbilirubinemia that resolved within 6 days without further action. The maximum tolerated dose was not reached. Three patients achieved complete responses, 1 each at 30, 120, and 150 μg/kg Q3W. PK studies showed marked interpatient variability, with target-mediated drug disposition seeming to contribute to time- and dose-dependent disposition. No clinically relevant anti–drug-antibody formation occurred. The trial was terminated in the dose-escalation phase because of slow accrual. This trial was registered at www.clinicaltrials.gov as NCT02669264.
Nickel allergy is associated with wheezing and asthma in a cohort of young German adults: results from the SOLAR study
Authors: Kolberg Laura , Forster Felix , Gerlich Jessica , Weinmayr Gudrun , Genuneit Jon , Windstetter Doris , Vogelberg Christian , von Mutius Erika , Nowak Dennis , Drexler Hans , Sch�fer Torsten , Radon Katja
Published: February 2020

Background

Nickel allergy is the most prevalent contact allergy. It belongs to a different hypersensitivity type to asthma and rhinoconjunctivitis. The aim of this analysis was to assess whether self-reported nickel allergy is associated with incident wheezing, asthma and rhinoconjunctivitis in young German adults, taking into account potential effect modification by sex.

Methods

In total, 2051 (70.6%) participants aged 19�24 years took part in the second phase of SOLAR (Study on Occupational Allergy Risks), a follow-up study of ISAAC II (the second phase of the International Study of Asthma and Allergies in Childhood) in Germany. Self-reported nickel allergy, as well as having pierced ears, and the three outcomes incident wheezing, asthma and rhinoconjunctivitis, were analysed stratified for sex. Logistic regression adjusted for potential confounders was performed.

Results

An association between self-reported nickel allergy and incident wheezing was observed for men and women, while only in males did pierced ears show a significant association with the outcome (adjusted OR 2.26, 95% CI 1.10�4.62). Also only in males, self-reported nickel allergy was associated with elevated odds for incident asthma (adjusted OR 4.34, 95% CI 1.22�15.41). Neither in men nor in women was a significant association observed for incident rhinoconjunctivitis.

Conclusion

Our results suggest that self-reported nickel allergy is associated with incident wheezing. Whether this association is due to environmental or genetic predisposition, or due to an overlap of the mechanisms of type I and type IV hypersensitivity, needs to be elucidated.
Flexible Bio-tensegrity Manipulator with Multi-degree of Freedom and Variable Structure
Authors: Wei Dunwen , Gao Tao , Mo Xiaojuan , Xi Ruru , Zhou Cong
Published: February 2020

Conventional manipulators with rigid structures and stiffness actuators have poor flexibility, limited obstacle avoidance capability, and constrained workspace. Some developed flexible or soft manipulators in recent years have the characteristics of infinite degrees of freedom, high flexibility, environmental adaptability, and extended manipulation capability. However, these existing manipulators still cannot achieve the shrinking motion and independent control of specified segments like the animals, which hinders their applications. In this paper, a flexible bio-tensegrity manipulator, inspired by the longitudinal and transversal muscles of octopus tentacles, was proposed to mimic the shrinking behavior and achieve the variable motion patterns of each segment. Such proposed manipulator uses the elastic spring as the backbone, which is driven by four cables and has one variable structure mechanism in each segment to achieve the independent control of each segment. The variable structure mechanism innovatively contains seven lock-release states to independently control the bending and shrinking motion of each segment. After the kinematic modeling and analysis, one prototype of such bionic flexible manipulator was built and the open-loop control method was proposed. Some proof-of-concept experiments, including the shrinking motion, bending motion, and variable structure motion, were carried out by controlling the length of four cables and changing the lock-release states of the variable structure mechanism, which validate the feasibility and validity of our proposed prototype. Meanwhile, the experimental results show the flexible manipulator can accomplish the bending and shrinking motion with the relative error less than 6.8% through the simple independent control of each segment using the variable structure mechanism. This proposed manipulator has the features of controllable degree-of-freedom in each segment, which extend their environmental adaptability, and manipulation capability.
Steam treatment to enhance rice straw binderless board focusing hemicellulose and cellulose decomposition products
Authors: Kurokochi Yoko , Sato Masatoshi
Published: February 2020

Rice straw is a troublesome biomass for an industrial application because of its high silica content and the wax-like substances covering the surface. At manufacturing binderless boards, which are considered environmentally friendly as they do not contain synthetic resins, rice straw silica contributed to water resistance, while the wax-like substances adversely affected self-bonding. This study investigated the effects of steam treatment on the self-bonding of binderless boards manufactured from rice straw. The chemical changes during steam treatment were examined by gas chromatography–mass spectrometry (GC–MS), and their influence on the bonding properties is discussed. Internal bonding strength and water resistance significantly increased by steam treatment. They also increased with increasing pressing temperature, and decreasing particle size. GC/MS analysis showed that not only hemicellulose and lignin, but also amorphous cellulose was decomposed during the steam treatment. Among the degradation products, 5-hydroxymethylfurfural was suggested to contribute to self-bonding during hot-pressing, while furfural was vaporized from the rice straw. Fine-grinding to below 150 μm after steam treatment resulted in high water resistance and an internal bonding strength of 0.6 MPa, which met the Japan Industrial Standards (JIS) requirement for Type-30 medium-density fiberboard (MDF). This mild pretreatment offers an alternative to steam explosion.
LINC00511 promotes proliferation and invasion by sponging miR-515-5p in gastric cancer
Authors: Wang Di , Liu Ketong , Chen Erdong
Published: February 2020

Background

Long non-coding RNAs (lncRNAs) are known to be involved in tumorigenesis. The functions of LINC00511 in gastric cancer are poorly understood.

Methods

Quantitative RT-PCR was performed to investigate the levels of LINC00511 in gastric cancer tissues and cell lines. CCK-8, flow cytometry, wound-healing and Transwell assays were performed to examine cellular functions. The underlying regulatory mechanisms of LINC00511 in gastric cancer progression were determined using luciferase reporter and RIP assays.

Results

LINC00511 levels were significantly higher in gastric cancer tissues and cell lines than in normal samples. The high expression of LINC00511 in gastric cancer patient samples positively correlated with advanced clinical characters and poor prognosis. Depleting LINC00511 reduced tumor cell proliferation, migration and invasion, slowed tumor growth, and accelerated cell apoptosis. Our mechanistic study results indicated that LINC00511 promotes gastric cancer progression in a miR-515-5p-dependent manner.

Conclusion

We established that LINC00511 may contribute to the proliferation and invasion of gastric cancer cells by modulating miR-515-5p, indicating that LINC00511 may be a potential molecular target for the development of anti-cancer drugs.
Correction to: Comparison of hepatitis B vaccine efficacy in Japanese students: a retrospective study
Authors: Ogawa Masanori , Akine Dai , Sasahara Teppei
Published: February 2020

Following publication of the original article [1], the authors spotted errors in their paper concerning the positive rate in the right side in Table 2.
Identification of transcriptome and fluralaner responsive genes in the common cutworm Spodoptera litura Fabricius, based on RNA-seq
Authors: Jia Zhong-Qiang , Liu Di , Peng Ying-Chuan , Han Zhao-Jun , Zhao Chun-Qing , Tang Tao
Published: February 2020

Background

Fluralaner is a novel isoxazoline insecticide with a unique action site on the γ-aminobutyric acid receptor (GABAR), shows excellent activity on agricultural pests including the common cutworm Spodoptera litura, and significantly influences the development and fecundity of S. litura at either lethal or sublethal doses. Herein, Illumina HiSeq Xten (IHX) platform was used to explore the transcriptome of S. litura and to identify genes responding to fluralaner exposure.

Results

A total of 16,572 genes, including 451 newly identified genes, were observed in the S. litura transcriptome and annotated according to the COG, GO, KEGG and NR databases. These genes included 156 detoxification enzyme genes [107 cytochrome P450 enzymes (P450s), 30 glutathione S-transferases (GSTs) and 19 carboxylesterases (CarEs)] and 24 insecticide-targeted genes [5 ionotropic GABARs, 1 glutamate-gated chloride channel (GluCl), 2 voltage-gated sodium channels (VGSCs), 13 nicotinic acetylcholine receptors (nAChRs), 2 acetylcholinesterases (AChEs) and 1 ryanodine receptor (RyR)]. There were 3275 and 2491 differentially expressed genes (DEGs) in S. litura treated with LC30 or LC50 concentrations of fluralaner, respectively. Among the DEGs, 20 related to detoxification [16 P450s, 1 GST and 3 CarEs] and 5 were growth-related genes (1 chitin and 4 juvenile hormone synthesis genes). For 26 randomly selected DEGs, real-time quantitative PCR (RT-qPCR) results showed that the relative expression levels of genes encoding several P450s, GSTs, heat shock protein (HSP) 68, vacuolar protein sorting-associated protein 13 (VPSAP13), sodium-coupled monocarboxylate transporter 1 (SCMT1), pupal cuticle protein (PCP), protein takeout (PT) and low density lipoprotein receptor adapter protein 1-B (LDLRAP1-B) were significantly up-regulated. Conversely, genes encoding esterase, sulfotransferase 1C4, proton-coupled folate transporter, chitinase 10, gelsolin-related protein of 125 kDa (GRP), fibroin heavy chain (FHC), fatty acid synthase and some P450s were significantly down-regulated in response to fluralaner.

Conclusions

The transcriptome in this study provides more effective resources for the further study of S. litura whilst the DEGs identified sheds further light on the molecular response to fluralaner.
Transcriptome profiling of Fagopyrum tataricum leaves in response to lead stress
Authors: Wang Lei , Zheng Bei , Yuan Yong , Xu Quanle , Chen Peng
Published: February 2020

Background

Lead (Pb) pollution is a widespread environmental problem that is harmful to living organisms. Tartary buckwheat (Fagopyrum tataricum), a member of the family Polygonaceae, exhibits short growth cycles and abundant biomass production, could be an ideal plant for phytoremediation due to its high Pb tolerance. Here, we aimed to explore the molecular basis underlying the responses of this plant to Pb stress.

Results

In our study, ultrastructural localization assays revealed that Pb ions primarily accumulate in leaf vacuoles. RNA deep sequencing (RNA-Seq) of tartary buckwheat leaves was performed on two Pb-treated samples, named Pb1 (2000 mg/kg Pb (NO3)2) and Pb2 (10,000 mg/kg Pb (NO3)2), and a control (CK). A total of 88,977 assembled unigenes with 125,203,555 bases were obtained. In total, 2400 up-regulated and 3413 down-regulated differentially expressed genes (DEGs) were identified between CK and Pb1, and 2948 up-regulated DEGs and 3834 down-regulated DEGs were generated between CK and Pb2, respectively. Gene Ontology (GO) and pathway enrichment analyses showed that these DEGs were primarily associated with ‘cell wall’, ‘binding’, ‘transport’, and ‘lipid and energy’ metabolism. The results of quantitative real-time PCR (qRT-PCR) analyses of 15 randomly selected candidate DEGs and 6 regulated genes were consistent with the results of the transcriptome analysis. Heterologous expression assays in the yeast strain Δycf1 indicated that overexpressing CCCH-type zinc finger protein 14 (ZFP14) enhanced sensitivity to Pb2+, while 5 other genes, namely, metal transporter protein C2 (MTPC2), phytochelatin synthetase-like family protein (PCSL), vacuolar cation/proton exchanger 1a (VCE1a), natural resistance-associated macrophage protein 3 (Nramp3), and phytochelatin synthetase (PCS), enhanced the Pb tolerance of the mutant strain.

Conclusion

Combining our findings with those of previous studies, we generated a schematic model that shows the metabolic processes of tartary buckwheat under Pb stress. This study provides important data for further genomic analyses of the biological and molecular mechanisms of Pb tolerance and accumulation in tartary buckwheat.
Effects of gestational diabetes mellitus on risk of adverse maternal outcomes: a prospective cohort study in Northwest Ethiopia
Authors: Muche Achenef Asmamaw , Olayemi Oladapo O. , Gete Yigzaw Kebede
Published: February 2020

Background

Gestational diabetes mellitus is a leading medical condition woman encounter during pregnancy with serious short- and long-term consequences for maternal morbidity. However, limited evidence was available on potential impacts of gestational diabetes mellitus using updated international diagnostic criteria on adverse maternal outcomes. Therefore, this study aimed to assess the effects of gestational diabetes mellitus on the risk of adverse maternal outcomes in Northwest Ethiopia.

Methods

A prospective cohort study was conducted among pregnant women followed from pregnancy to delivery. Gestational diabetes mellitus status was determined by using a two-hour 75 g oral glucose tolerance test and based on updated international diagnostic criteria. Multivariable log-binomial model was used to examine the effects of gestational diabetes mellitus on the risk of adverse maternal outcomes.

Results

A total of 694 women completed the follow-up and included in the analysis. Women with gestational diabetes mellitus had a higher risk of composite adverse maternal outcome (ARR=1.58, 95% CI: 1.22, 2.04), caesarean delivery (ARR=1.67; 95%: 1.15, 2.44), pregnancy induced hypertension (ARR= 3.32; 95%: 1.55, 7.11), premature rupture of membranes (ARR= 1.83; 95%: 1.02, 3.27), antepartum hemorrhage (ARR= 2.10; 95%: 1.11, 3.98) and postpartum hemorrhage (ARR= 4.85; 95%:2.28, 10.30) compared to women without gestational diabetes mellitus.

Conclusions

Gestational diabetes mellitus increased the risk of adverse maternal outcomes. This implies that maternal care and intervention strategies relating to women with gestational diabetes mellitus should be strengthened.
Review of metastatic colorectal cancer treatment pathways and early clinical experience of trifluridine/tipiracil in the UK named patient programme
Authors: Iveson Timothy , Carter Angela M. , Shiu Kai-Keen , Spooner Clare , Stevens Daniel , Mullamitha Saifee
Published: February 2020

Background

The standard first- and second- line chemotherapy backbone regimens for metastatic colorectal cancer (mCRC) are 5-fluorouracil (5-FU)/capecitabine-based with addition of irinotecan or oxaliplatin. Until recently, evidence for optimal sequencing post second-line was sparse. Trifluridine/tipiracil (indicated for mCRC and gastric cancer after standard chemotherapies) was made available to UK patients via a named patient programme (NPP) before receiving marketing authorisation in Europe in 2016, allowing characterisation of UK treatment pathways, and evaluation of trifluridine/tipiracil in a UK non-trial population.

Methods

Data collected routinely for the NPP were analysed to describe the patient demographics, clinical characteristics and treatment pathways. Patients eligible for the programme were adults (≥18 years) with histologically or cytologically confirmed mCRC who had previously received chemotherapy treatment(s).

Results

Of the 250 eligible patients enrolled in the NPP, 194 patients received ≥1 dose of trifluridine/tipiracil and 56 patients did not receive trifluridine/tipiracil. The following results are reported first for patients who received trifluridine/tipiracil and second for those who did not receive trifluridine/tipiracil: median (IQR) age was 63.0 (54.0–69.0) and 62.0 (54.8–69.0) years; Eastern Cooperative Oncology Group performance status score was 0 for 28 and 14%, 1 for 65 and 70%, 2 for 7 and 16%. In terms of previous systemic treatments 47 and 43% had 2 prior lines of therapy. FOLFOX-, FOLFIRI- and CAPOX-based therapies were the most common first-line regimens in patients receiving trifluridine/tipiracil (37, 35 and 21%, respectively), and in patients not receiving trifluridine/tipiracil (41, 30 and 20%, respectively). Second-line treatment regimens in patients receiving and not receiving trifluridine/tipiracil were most commonly FOLFIRI-based (48 and 41%, respectively) and FOLFOX-based (19 and 21%, respectively). Patients received a median of 2 cycles of trifluridine/tipiracil with a median treatment duration of 1.8 (95% CI: 1.8–2.4) months. In patients who discontinued treatment due to disease progression, the median progression-free duration was 2.8 (95% CI: 2.4–2.9) months.

Conclusions

The results highlight the number of treatment pathways used to treat mCRC in routine UK clinical practice prior to the marketing authorisation and National Institute for Health and Care Excellence approval of trifluridine/tipiracil and highlight the lack of clinical guidelines for mCRC.
IL-36 s in the colorectal cancer: is interleukin 36 good or bad for the development of colorectal cancer?
Authors: Chen Feier , Qu Meng , Zhang Feng , Tan Zhenyu , Xia Qinghua , Hambly Brett D. , Bao Shisan , Tao Kun
Published: February 2020

Background and aims

Colorectal cancer (CRC) is a major killer. Host immunity is important in tumorigenesis. Direct comparison among IL-36α, IL-36β and IL-36γ in the prognosis of CRC is unclear.

Methods

CRC tissue arrays were generated from colorectostomy samples with TNM stage, invasion depth and the demography of these patients (n = 185). Using immunohistochemistry/histopathology, IL-36α, IL-36β and IL-36γ were determined, in comparison to non-cancer tissues.

Results

A significant association was observed between colonic IL-36α, IL-36β or IL-36γ and the presence of cancer (with all P < 0.0001). Using ROC curve analysis, specificity and sensitivity of IL-36α, IL-36β or IL-36γ were confirmed, with area under the curve (AUC) values of 0.68, 0.73 and 0.65, respectively. Significant differences in survival were observed between IL-36αhigh and IL-36αlow (P = 0.003) or IL-36γhigh and IL-36γlow (P = 0.03). Survival curves varied significantly when further stratification into sub-groups, on the basis of combined levels of expression of two isotypes of IL-36 was undertaken. A significant difference was observed when levels of IL-36α and IL-36β were combined (P = 0.01), or a combination of IL-36α plus IL-36γ (P = 0.002). The sub-groups with a combination of IL-36αhigh plus IL-36βhigh, or IL-36αhigh plus IL-36γlow exhibited the longest survival time among CRC patients. In contrast, the sub-groups of IL-36αlow plus IL-36βhigh or IL-36αlow plus IL-36γhigh had the shortest overall survival. Using the log-rank test, IL-36αhigh expression significantly improved survival in patients with an invasion depth of T4 (P < 0.0001), lymph node metastasis (P = 0.04), TNM III-IV (P = 0.03) or with a right-sided colon tumour (P = 0.02). Similarly, IL-36γlow expression was significantly associated with improved survival in patients with no lymph node metastasis (P = 0.008), TNM I-II (P = 0.03) or with a left-sided colon tumour (P = 0.05). Multivariate analysis demonstrated that among IL-36α, IL-36β and IL-36γ, only IL-36α (HR, 0.37; 95% CI, 0.16–0.87; P = 0.02) was an independent factor in survival, using Cox proportional hazards regression analysis.

Conclusion

IL-36α or IL-36γ are reliable biomarkers in predicting the prognosis of CRC during the later or early stages of the disease, respectively. Combining IL-36α plus IL-36γ appears to more accurately predict the postoperative prognosis of CRC patients. Our data may be useful in the management of CRC.
Correction to: The effect of youths as change agents on cardiovascular disease risk factors among adult neighbours: a cluster randomised controlled trial in Sri Lanka
Authors: Chandraratne Nadeeka , Yamaguchi Miwa , Indrawansa Susantha , Gunawardena Nalika , Kuwahara Keisuke , Islam Zobida , Kawasaki Yohei , Mizoue Tetsuya , Samarasinghe Diyanath
Published: February 2020

It was highlighted that in the original article [1] the selection process was not described clearly enough to avoid confusion under the heading of the Target of Outcomes in the Methods section.
The functional outcomes and complications of different reconstruction methods for Giant cell tumor of the distal radius: comparison of Osteoarticular allograft and three-dimensional-printed prosthesis
Authors: Wang Yitian , Min Li , Lu Minxun , Zhou Yong , Wang Jie , Zhang Yuqi , Yu Xinzhu , Tang Fan , Luo Yi , Duan Hong , Tu Chongqi
Published: February 2020

Background

En bloc excision has been increasingly used for the management of giant cell tumors (GCTs) in the distal radius. An osteoarticular allograft has been used extensively for decades, and custom-made prosthesis reconstruction has been more recently applied. We aimed to compare the clinical outcomes of the two procedures.

Methods

We retrospectively analyzed 30 patients with Campanacci III or recurrent GCTs of the distal radius for follow-up at a mean of 33.2 months. In total, 15 underwent osteoarticular allograft reconstruction (allograft group) and 15 received cementless three-dimensional (3D)-printed prosthesis reconstruction (prosthesis group) between March 18, 2013, and May 20, 2018. All patients underwent by clinical and radiological examinations, including pre- and postoperative active range of motion (ROM) of the wrist, VAS score, grip strength, degenerative change of wrist, Mayo wrist score and Musculoskeletal Tumor Society (MSTS) score. Complications were evaluated using the Henderson classification.

Results

Both groups showed significantly increased ROM, grip strength, Mayo score and MSTS score postoperatively. Furthermore, the extension, flexion, MSTS, and Mayo score were significantly higher in the prosthesis group. There was no significant difference in grip strength and VAS between the groups. In allograft group, one patient had a late infection one had resorption of allograft without allograft bone fracture. and four had wrist subluxation. All patients had degenerative changes (mean 9 months). In the prosthesis group, three patients developed wrist subluxation, three had separation of the distal radioulnar joint, and none of the patients developed wrist degeneration.

Conclusions

Our study compared the objective functional outcomes and complications of two reconstructive methods for Campanacci III or recurrent GCT in the distal radius. 3D-printed prosthesis replacement can partially preserve wrist function better than allograft reconstruction in the short-term. During the design of 3D-printed prosthesis, preoperative morphological assessment of the affected proximal row carpal is helpful to control postoperative dislocation. After allograft reconstruction, wrist degeneration, which has been demonstrated in all patients, severely influence their wrist function. Therefore, compared to allograft reconstruction, 3D-printed prosthesis reconstruction has irreplaceable advantages at early-stage application, especially in wrist function, however, further studied with a larger number of cases and longer follow-up.
Comparison of the retroperitoneal versus Transperitoneal laparoscopic Adrenalectomy perioperative outcomes and safety for Pheochromocytoma: a meta-analysis
Authors: Jiang Yu-Li , Qian Lu-Jie , Li Zhen , Wang Kang-Er , Zhou Xie-Lai , Zhou Jin , Ye Chun-Hua
Published: February 2020

Background

To compare the perioperative outcomes and safety of transperitoneal laparoscopic adrenalectomy with those of retroperitoneal laparoscopic adrenalectomy for patients with pheochromocytoma.

Methods

We searched PubMed, EMBASE and the Cochrane Central Register for studies from 1999 to 2019 to assess the perioperative outcomes and safety of transperitoneal laparoscopic adrenalectomy and the retroperitoneal approach for laparoscopic adrenalectomy in patients with pheochromocytoma. After data extraction and quality assessments, we used RevMan 5.2 to pool the data.

Results

Four retrospective studies were obtained in our meta-analysis. Patients who underwent retroperitoneal laparoscopic adrenalectomy were associated with shorter operative time (WMD: 34.91, 95% CI: 27.02 to 42.80, I2 = 15%; p < 0.01), less intraoperative blood loss (WMD: 139.32, 95% CI: 125.38 to 153.26, I2 = 0, p < 0.01), and a shorter hospital stay (WMD: 2, 95% CI: 1.18 to 2.82, I2 = 82%, p < 0.01) than patients who underwent transperitoneal laparoscopic adrenalectomy. No significant differences were found in the complication rate (OR: 1.58, 95% CI: 0.58 to 4.33, I2 = 0; p = 0.38) or in the incidence of hemodynamic crisis (OR: 0.74, 95% CI: 0.19 to 2.94, p = 0.67) between the two groups.

Conclusion

Retroperitoneal laparoscopic adrenalectomy could achieve better perioperative outcomes than the transperitoneal approach for patients with pheochromocytoma.
Synthesis of crocetin derivatives and their potent inhibition in multiple tumor cells proliferation and inflammatory property of macrophage
Authors: Wang Mao-Ze , Gao Jin , Chu Yang , Niu Jie , Chen Ming , Shang Qiang , Peng Li-Hua , Jiang Zhi-Hong
Published: February 2020

Background

Crocetin is a major active component of saffron, which has a wide range of pharmacological effects. However, due to its low solubility, the pharmacological effects of crocetin cannot be better utilized.

Methods

In this study, we modified the chemical structure of crocetin by conjugating with ethylamine and 4-Fluorbenzylamine to enhance its solubility and biological activities. The solubility and the influence of synthesized derivatives on the proliferation of tumor cells and the inflammatory effect of macrophage were investigated.

Results

It was shown that, compared with the crocetin, the synthesized derivatives have much higher solubility. Moreover, the inhibitory effect of the derivatives on varieties of tumor cells, including human ovarian carcinoma cell line, human lung cancer cell line, rat melanoma cell line was enhanced after the modification. Besides that, the derivatives were improved for the anti-inflammatory efficacy with the cytotoxicity decreased.

Conclusions

The synthesized derivatives were shown for their good solubility and the great potential in tumor and inflammation treatment.
Review of tuberculosis treatment outcome reporting system in Denmark, a retrospective study cohort study from 2009 through 2014
Authors: Holden Inge K. , Andersen Peter H. , Wejse Christian , Lillebaek Troels , Johansen Isik S.
Published: February 2020

Background

In Denmark, reporting of tuberculosis (TB) treatment outcome is voluntary and data incomplete. In the European Centre for Disease Prevention and Control most recent report presenting data from 2017, only 53.9% of Danish pulmonary TB cases had a reported outcome. Monitoring of TB treatment outcome is not feasible based on such limited results. In this retrospective study from 2009 to 2014, we present complete treatment outcome data and describe characteristics of cases lost to follow up.

Methods

All cases notified from 2009 through 2014 were reviewed. Hospital records were examined, and TB treatment outcome was categorized according to the World Health Organization’s (WHO) definitions.

Results

A total of 2131 TB cases were included. Treatment outcome was reported to the Surveillance Unit in 1803 (84.6%) cases, of which 468 (26.0%) were reclassified. For pulmonary TB, 339 (28.9%) cases were reclassified between cured and treatment completed.

Overall, the proportion of cases who achieved successful treatment outcome increased from 1488 (70.4%) to 1748 (81.8%).

Conclusion

A high number of cases were reclassified during the review process. Increased focus on correct treatment outcome reporting is necessary in Denmark. A more comprehensive and exhaustive categorization of TB treatment outcome could be beneficial, especially for cases where collection of sputum or tissue towards the end of treatment is challenging.
Institutional strategies as a mechanism to rationalize the negative effects of the judicialization of access to medicine in Brazil
Authors: Chagas Virginia Oliveira , Provin Mércia Pandolfo , Mota Pedro Augusto Prado , Guimarães Rafael Alves , Amaral Rita Goreti
Published: February 2020

Background

Recently, the Executive Branch and Judiciary in Brazil increased spending due to larger numbers of lawsuits that forced the State to provide health goods and services. This phenomenon, known as health judicialization, has created challenges and required the Executive Branch and Judiciary to create institutional strategies such as technical chambers and departments to reduce the social, economic and political distortions caused by this phenomenon. This study aims to evaluate the effects of two institutional strategies deployed by a Brazilian municipality in order to cope with the economic, social and political distortions caused by the phenomenon of health judicialization regarding access to medicines.

Methods

A longitudinal study was carried out in a capital in the Central-West Region of Brazil. A sample of 511 lawsuits was analyzed. The variables were placed into three groups: the sociodemographic characteristics and the plaintiffs’ disease, the characteristics of the claimed medical products and the institutional strategies. To analyze the effect of the interventions on the total cost of the medicines in the lawsuits, bivariate and multivariate linear regressions with variance were performed. For the categorical outcomes, Poisson regressions were performed with robust variance, using a significance level of 5%.

Results

A reduction in the costs of medicines in the lawsuits and of the requests for medicines within the SUS formulary was verified after the deployment of the Department of Assessment of Nonstandardized Medicines (DAMNP) and the Technical Chamber of Health Assessment (CATS); an increase in processed prescriptions from the Brazilian Universal Health System was observed after the deployment of the CATS; and an increase in medicines outside the SUS formulary without a therapeutic alternative was verified after the CATS.

Conclusion

The institutional strategies deployed were important tools to reduce the high costs of the medicines in the lawsuits. In addition, they represented a step forward for the State, provided a benefit to society and indicated a potential path for the health and justice systems of other countries that also face problems caused by the judicialization of health.
Livestock owners’ anthrax prevention practices and its associated factors in Sekota Zuria district, Northeast Ethiopia
Authors: Seid Kibeb , Shiferaw Atsede Mazengia , Yesuf Nurhusien Nuru , Derso Terefe , Sisay Mekonnen
Published: February 2020

Background

In Ethiopia, the second most prioritized of the zoonotic diseases next to rabies is anthrax. About 50.6% of anthrax cases and 33.3% of deaths of livestock have been reported from Wag-Himra Zone, where appropriate anthrax prevention practices are not implemented by the owners of the animals. Thus, the aim of this study was to determine the extent of appropriate anthrax prevention practices of livestock owners and associated factors in Sekota Zuria district, northwest Ethiopia.

Results

Twenty-five percent (95% CI: 25.2, 26.1%) of the livestock owners implemented appropriate anthrax prevention. Three quarters (74%) of the owners consumed infected meat; more than three quarters (78%) used the skins and hides of animals found dead with anthrax. The odds of appropriate anthrax prevention practices were higher among livestock owners with positive attitude (AOR = 4.16, 95% CI: 2.72, 6.37), who received health education (AOR = 2.00, 95% CI: 1.21, 3.28) and owners who lived in urban areas (AOR = 2.62, 95% CI: 1.43, 4.77) compared to their counterparts. Ability to read and write (AOR = 2.76, 95% CI: 1.74, 4.37), and primary (AOR = 3.6, 95% CI: 1.74, 4.37) or secondary school and above education (AOR = 4.24, 95% CI: 1.61, 11.13) were significantly associated with appropriate anthrax prevention practices.

Conclusion

In Sekota Zuria district, only one quarter of the livestock owners were aware of appropriate anthrax prevention practices. Thus, implementing effective health education and creating positive attitude are vital to improve anthrax prevention practices in the area.
Phenotypic antimicrobial resistance in Escherichia coli strains isolated from swine husbandries in North Western Germany – temporal patterns in samples from laboratory practice from 2006 to 2017
Authors: Moennighoff C. , Thomas N. , Nienhaus F. , Hartmann M. , Menrath A. , Merkel J. , Detlefsen H. , Kreienbrock L. , Hennig-Pauka I.
Published: February 2020

Background

Since 2011, antibiotic usage has decreased continuously in livestock in Germany. Whether this is accompanied by a reduction in bacterial antimicrobial resistance has not been proven so far. In this study 3054 Escherichia coli (E. coli) isolates from pigs which had suffered from disease on 2161 farms in North Western Germany were evaluated retrospectively from 2006 to 2017 for trends in their antimicrobial resistance pattern. Data were substantially related to the “pre-reduction period” and were therefore suggested as a basis for this task.

Minimal inhibitory concentrations for selected antimicrobial substances were evaluated for E. coli strains isolated from different organs of diseased swine sampled for routine diagnostic. In total, 81% of E. coli were isolated from faeces or the gastrointestinal tract, 11% from the genito-urinary tract and 8% from other organs. Susceptibility testing and classification of isolates in accordance with clinical cut-offs followed the Clinical and Laboratory Standards Institute (CLSI). If no clinical cut-offs were available for the respective combination of species, substance and organ, other published clinical cut-offs were used.

Results

Differences in susceptibility patterns between isolates from the gastrointestinal and genito-urinary tract were found for most substances. Isolates from the genito-urinary tract were less frequently resistant to ampicillin, apramycin, colistin, neomycin, spectinomycin and tetracycline and more frequently resistant to enrofloxacin and florfenicol.

A multifactorial logistic regression model revealed time-dependent decreases in frequency of resistant isolates for neomycin, spectinomycin and tetracycline. For colistin, the highest percentage of resistant isolates with 16.0% was found in 2015 followed by a decrease to the level of 2009–2010 in 2017. A decrease in frequencies of ampicillin-resistant isolates was dependent on the age-group and time period. Irrespective of the year, less than 15% E. coli isolates were resistant to apramycin, cephalosporins, colistin, enrofloxacin, florfenicol, gentamicin and neomycin.

Conclusion

An overall time-dependent decrease in the percentage of resistant E. coli isolates was found for some substances. These data from diseased animals indicate an impact of a general reduction in antibiotic usage on development of bacterial antimicrobial resistance in the field and can support the decision-making of swine practitioners for treatment options in swine.
Gene therapy-emulating small molecule treatments in cystic fibrosis airway epithelial cells and patients
Authors: Yang Q. , Soltis A. R. , Sukumar G. , Zhang X. , Caohuy H. , Freedy J. , Dalgard C. L. , Wilkerson M. D. , Pollard H. B. , Pollard B. S.
Published: February 2020

Background

Several small molecule corrector and potentiator drugs have recently been licensed for Cystic Fibrosis (CF) therapy. However, other aspects of the disease, especially inflammation, are less effectively treated by these drugs. We hypothesized that small molecule drugs could function either alone or as an adjuvant to licensed therapies to treat these aspects of the disease, perhaps emulating the effects of gene therapy in CF cells. The cardiac glycoside digitoxin, which has been shown to inhibit TNFα/NFκB signaling in CF lung epithelial cells, may serve as such a therapy.

Methods

IB3–1 CF lung epithelial cells were treated with different Vertex (VX) drugs, digitoxin, and various drug mixtures, and ELISA assays were used to assess suppression of baseline and TNFα-activated secretion of cytokines and chemokines. Transcriptional responses to these drugs were assessed by RNA-seq and compared with gene expression in AAV-[wildtype]CFTR-treated IB3–1 (S9) cells. We also compared in vitro gene expression signatures with in vivo data from biopsied nasal epithelial cells from digitoxin-treated CF patients.

Results

CF cells exposed to digitoxin exhibited significant suppression of both TNFα/NFκB signaling and downstream secretion of IL-8, IL-6 and GM-CSF, with or without co-treatment with VX drugs. No evidence of drug-drug interference was observed. RNA-seq analysis showed that gene therapy-treated CF lung cells induced changes in 3134 genes. Among these, 32.6% were altered by digitoxin treatment in the same direction. Shared functional gene ontology themes for genes suppressed by both digitoxin and gene therapy included inflammation (84 gene signature), and cell-cell interactions and fibrosis (49 gene signature), while genes elevated by both were enriched for epithelial differentiation (82 gene signature). A new analysis of mRNA data from digitoxin-treated CF patients showed consistent trends in expression for genes in these signatures.

Conclusions

Adjuvant gene therapy-emulating activities of digitoxin may contribute to enhancing the efficacy of currently licensed correctors and potentiators in CF patients.
6′-O-galloylpaeoniflorin regulates proliferation and metastasis of non-small cell lung cancer through AMPK/miR-299-5p/ATF2 axis
Authors: Gao Jinying , Song Lei , Xia Huan , Peng Liping , Wen Zhongmei
Published: February 2020

Background

Recent studies have shown 6'-O-galloylpaeoniflorin (GPF), a nature product extracted from the roots of paeoniflorin exerts anti-oxidant and anti-inflammatory activities. However, the effects of GPF on the proliferation and invasion in non-small cell lung cancer (NSCLC) cells have not been clarified.

Methods

MTT assay was performed to determine the cytotoxicity of GPF treatment on NSCLC cells. Colony formation assay, cell scratch test and transwell assay were performed to determine the proliferation and invasion of NSCLC cells in vitro, respectively. An A549 cell xenograft mouse model was performed to confirm the growth of NSCLC cells in vivo. Western blotting was used to measure the levels of activating transcription factor 2 (ATF2), AMP-activated protein kinase (AMPK) and phosph-AMPK (p-AMPK). Luciferase assay was used to validate the binding of miR-299-5p on the 3' untranslated region (UTR) of ATF2.

Results

Administration of GPF (50 or 100 μM) was significantly cytotoxic to A549 cells and H1299 cells, as well as inhibited the clonality, invasion and metastasis of NSCLC cells in vitro. GPF treatment also inhibited the tumor growth of NSCLC cell mouse xenografts in vivo. Exotic expression of miR-299-5p significantly inhibited the growth of NSCLC cells in vitro and in vivo. Downregulation of miR-299-5p expression attenuated the inhibition of the proliferation and metastasis of non-small cell lung cancer cells by GPF treatment. miR-299-5p significantly decreased ATF2 mRNA and protein levels in A549 cells (p < 0.05). Overexpression of ATF2 blocked the inhibitory effect of miR-299-5p on the proliferation and invasiveness of A549 cells.

Conclusions

GPF regulates miR-299-5p/ATF2 axis in A549 cells via the AMPK signalling pathway, thereby inhibiting the proliferation and metastasis of non-small cell lung cancer cells.
Production and characterization of yeasts grown on media composed of spruce-derived sugars and protein hydrolysates from chicken by-products
Authors: Lapeña David , Kosa Gergely , Hansen Line D. , Mydland Liv T. , Passoth Volkmar , Horn Svein J. , Eijsink Vincent G. H.
Published: February 2020

Background

A possible future shortage of feed protein will force mankind to explore alternative protein sources that can replace conventional soymeal or fishmeal. Several large industrial organic side-streams could potentially be upgraded to feed protein using a fermentation process to generate single cell protein. Yeast is the most widely accepted microorganism for production of single cell protein, because of its superior nutritional quality and acceptability among consumers. Here, we have assessed the growth of four different yeasts, Cyberlindnera jadinii, Wickerhamomyces anomalus, Blastobotrys adeninivorans and Thermosacc® Dry (Saccharomyces cerevisiae), on media composed of enzymatically saccharified sulfite-pulped spruce wood and hydrolysates of by-products from chicken, and we have characterized the resulting yeast biomass.

Results

Generally, the yeast grew very well on the spruce- and chicken-based medium, with typical yields amounting to 0.4–0.5 g of cell dry weight and 0.2–0.3 g of protein per g of sugar. B. adeninivorans stood out as the most versatile yeast in terms of nutrient consumption and in this case yields were as high as 0.9 g cells and 0.5 g protein per g of sugar. The next best performing yeast in terms of yield was W. anomalus with up to 0.6 g cells and 0.3 g protein per g sugar. Comparative compositional analyses of the yeasts revealed favorable amino acid profiles that were similar to the profiles of soymeal, and even more so, fish meal, especially for essential amino acids.

Conclusions

The efficient conversion of industrial biomass streams to yeast biomass demonstrated in this study opens new avenues towards better valorization of these streams and development of sustainable feed ingredients. Furthermore, we conclude that production of W. anomalus or B. adeninivorans on this promising renewable medium may be potentially more efficient than production of the well-known feed ingredient C. jadinii. Further research should focus on medium optimization, development of semi-continuous and continues fermentation protocols and exploration of downstream processing methods that are beneficial for the nutritional values of the yeast for animal feed.