bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic factors in pulmonary metastasectomy and efficacy of repeat pulmonary metastasectomy from colorectal cancer
Authors: Fukada Masahiro , Matsuhashi Nobuhisa , Takahashi Takao , Tanaka Yoshihiro , Okumura Naoki , Yamamoto Hirotaka , Shirahashi Koyo , Iwata Hisashi , Doi Kiyoshi , Yoshida Kazuhiro
Published: November 2020

Background

The rate of pulmonary metastasectomy from colorectal cancer (CRC) has increased with recent advances in chemotherapy, diagnostic techniques, and surgical procedures. The purpose of this study was to investigate the prognostic factors for response to pulmonary metastasectomy and the efficacy of repeat pulmonary metastasectomy.

Methods

This study was a retrospective, single-institution study of 126 CRC patients who underwent pulmonary metastasectomy between 2000 and 2019 at the Gifu University Hospital.

Results

The 3- and 5-year survival rates were 84.9% and 60.8%, respectively. Among the 126 patients, 26 (20.6%) underwent a second pulmonary metastasectomy for pulmonary recurrence after initial pulmonary metastasectomy. Univariate analysis of survival identified seven significant factors: (1) gender (p = 0.04), (2) past history of extra-thoracic metastasis (p = 0.04), (3) maximum tumor size (p = 0.002), (4) mediastinal lymph node metastasis (p = 0.02), (5) preoperative carcinoembryonic antigen (CEA) level (p = 0.01), (6) preoperative carbohydrate antigen 19-9 (CA19-9) level (p = 0.03), and (7) repeat pulmonary metastasectomy for pulmonary recurrence (p < 0.001). On multivariate analysis, only mediastinal lymph node metastasis (p = 0.02, risk ratio 8.206, 95% confidence interval (CI) 1.566–34.962) and repeat pulmonary metastasectomy for pulmonary recurrence (p < 0.001, risk ratio 0.054, 95% CI 0.010–0.202) were significant. Furthermore, in the evaluation of surgical outcomes, the safety of second pulmonary metastasectomy was almost the same as that of initial pulmonary metastasectomy.

Conclusions

Repeat pulmonary metastasectomy is likely to be safe and effective for recurrent cases that meet the surgical criteria. However, mediastinal lymph node metastasis was a significant independent prognostic factor for worse overall survival.
Catechins from oolong tea improve uterine defects by inhibiting STAT3 signaling in polycystic ovary syndrome mice
Authors: Hong Ge , Wu Hao , Ma Shi-Tang , Su Zhe
Published: November 2020

Background

It is showed that inflammation is causative factor for PCOS, leading to a decline in ovarian fertility. Previous studies have reported that tea consumption can reduce the incidence of ovarian cancer. We speculate that catechins from oolong tea (Camellia sinensis (L.) O.Kuntze) may have a potential therapeutic effect on PCOS. This study aims to investigate the effects of oolong tea catechins on the uterus of polycystic ovary syndrome (PCOS) mice induced by insulin combined with human chorionic gonadotropin (hCG).

Methods

Sixty female mice were divided into 6 groups (n = 10): model, model + Metformin 200 mg/kg, model + catechins 25 mg/kg, model + catechins 50 mg/kg, and model + catechins 100 mg/kg. Another forty female mice were divided into 4 groups (n = 10): control, control + catechins 100 mg/kg, model, and model + catechins 100 mg/kg. Ovarian and uterine weight coefficients, sex hormone levels, glucose metabolism and insulin resistance, and ovarian and uterine pathology were examined. Changes in NF-κB-mediated inflammation, MMP2 and MMP9 expressions, and STAT3 signaling were evaluated in the uterus of mice.

Results

Catechins could effectively reduce the ovarian and uterine organ coefficients, reduce the levels of E2, FSH and LH in the blood and the ratio of LH/FSH, and improve glucose metabolism and insulin resistance in PCOS mice induced by insulin combined with hCG. In addition, catechins could significantly down-regulated the expression of p-NF-κB p65 in the uterus and the protein expressions of the pro-inflammatory factors (IL-1β, IL-6, and TNF-α). The expressions of mmp2 and mmp9 associated with matrix degradation in uterine tissue were also significantly down-regulated by catechins. Further, catechins significantly reduced the expression of p-STAT3 and increased the expression of p-IRS1 and p-PI3K in the uterus of PCOS mice.

Conclusion

Catechins from oolong tea can alleviate ovarian dysfunction and insulin resistance in PCOS mice by inhibiting uterine inflammation and matrix degradation via inhibiting p-STAT3 signaling.
KLF7: a new candidate biomarker and therapeutic target for high-grade serous ovarian cancer
Authors: De Donato Marta , Babini Gabriele , Mozzetti Simona , Buttarelli Marianna , Ciucci Alessandra , Arduini Gloria , De Rosa Maria Cristina , Scambia Giovanni , Gallo Daniela
Published: November 2020

Background

In spite of great progress in the surgical and clinical management, until now no significant improvement in overall survival of High-Grade Serous Ovarian Cancer (HGSOC) patients has been achieved. Important aspects for disease control remain unresolved, including unclear pathogenesis, high heterogeneity and relapse resistance after chemotherapy. Therefore, further research on molecular mechanisms involved in cancer progression are needed to find new targets for disease management. The Krüppel-like factors (KLFs) are a family of transcriptional regulators controlling several basic cellular processes, including proliferation, differentiation and migration. They have been shown to play a role in various cancer-relevant processes, in a context-dependent way.

Methods

To investigate a possible role of KLF family members as prognostic biomarkers, we carried out a bioinformatic meta-analysis of ovarian transcriptome datasets in different cohorts of late-stage HGSOC patients. In vitro cellular models of HGSOC were used for functional studies exploring the role of KLF7 in disease development and progression. Finally, molecular modelling and virtual screening were performed to identify putative KLF7 inhibitors.

Results

Bioinformatic analysis highlighted KLF7 as the most significant prognostic gene, among the 17 family members. Univariate and multivariate analyses identified KLF7 as an unfavourable prognostic marker for overall survival in late-stage TCGA-OV and GSE26712 HGSOC cohorts.

Functional in vitro studies demonstrated that KLF7 can play a role as oncogene, driving tumour growth and dissemination. Mechanistic targets of KLF7 included genes involved in epithelial to mesenchymal transition, and in maintaining pluripotency and self-renewal characteristics of cancer stem cells. Finally, in silico analysis provided reliable information for drug-target interaction prediction.

Conclusions

Results from the present study provide the first evidence for an oncogenic role of KLF7 in HGSOC, suggesting it as a promising prognostic marker and therapeutic target.
Psychometric evaluation of the Farsi version of the diabetes foot self‐care bahavior scale
Authors: Hasanpour Dehkordi Ali , Chin Yen‐Fan , Huang Tzu‐Ting , Ebadi Abbas , Ghanei Gheshlagh Reza
Published: November 2020

Background

Diabetes foot self‐care is one of the self‐management behaviors of diabetic patients leading to a reduction in the incidence of pressure ulcers and amputation. Having a valid, reliable, simple and comprehensive tool is essential in measuring the self‐care behavior of diabetic patients. The aim of this study was to evaluate the psychometric properties of the Farsi version of the diabetes foot self‐care bahavior scale (DFSBS) in Iran.

Methods

In this cross‐sectional and methodological study, 500 patients with type 2 diabetes were recruited by convenience sampling. Construct validity was assessed by exploratory factor analysis (over 300 patients) and confirmatory factor analysis (over 200 patients). Internal consistency was calculated by Cronbach's alpha coefficient and its stability was calculated by intraclass correlation coefficient (ICC).

Results

In the exploratory factor analysis, two self‐care factors related to feet and shoes were extracted which had specific values of 38.49 and 1.24, respectively, and were able to account for 56.22% of the total self‐care variance of diabetes foot. Confirmatory factor analysis had excellent fit model. The internal consistency and ICC of the whole instrument were 0.83 and 0.791 (95% CI: 0.575–0.925; P < 0.001), respectively.

Conclusions

The Farsi version of DFSBS (F‐DFSBS) has good validity and reliability, and due to its appropriate psychometric properties, this tool can be used in future studies.
Comparison of reversal of rat pulmonary fibrosis of nintedanib, pirfenidone, and human umbilical mesenchymal stem cells from Wharton’s jelly
Authors: Chu Kuo-An , Yeh Chang-Ching , Kuo Fu-Hsien , Lin Wen-Ren , Hsu Chien-Wei , Chen Tien-Hua , Fu Yu-Show
Published: November 2020

Background

The present study compared the effects of antifibrotic medications, pirfenidone, and nintedanib, with transplantation of human umbilical mesenchymal stem cells (HUMSCs) in restoring rat pulmonary fibrosis (PF).

Methods

A stable animal model was established via an intratracheal injection of 5 mg bleomycin (BLM). One single transplantation of 2.5× 107 HUMSCs or initiation of daily oral nintedanib/pirfenidone administration was performed on day 21 following BLM damage.

Results

Pulmonary function examination revealed that BLM rats exhibited a significant decrease in blood oxygen saturation and an increase in respiratory rates. While no significant improvements were found in BLM rats receiving nintedanib or pirfenidone, those who transplanted with HUMSCs showed a statistical amelioration in blood oxygen saturation and significant alleviation in respiratory rates. Quantification results revealed that a significant reduction in alveolar space and marked increases in substantial cell infiltration and collagen deposition in the left lungs of BLM rats. No significant alteration was observed in BLM rats administered nintedanib or pirfenidone. However, BLM rats transplanted with HUMSCs had a significant recovery in alveolar space and noticeable decreases in cell infiltration and collagen deposition. The inflammatory cell numbers in the bronchoalveolar lavage was increased in the BLM group. While the rats treated with nintedanib or pirfenidone had a lower cell number than the BLM group, a higher cell number was found as compared with the Normal group. In rats transplanted with HUMSCs, the cell number did not differ from the Normal group.

Conclusions

Transplantation of HUMSCs could effectively treat PF as opposed to the administration of anti-fibrotic drugs with nintedanib or pirfenidone with a significant better result in lung volume, pathological changes, lung function, and blood oxygen saturation.
Unexpected increase of myocardial extracellular volume fraction in low cardiovascular risk HIV patients
Authors: Borrazzo Cristian , d’Ettorre Gabriella , Ceccarelli Giancarlo , Pacilio Massimiliano , Santinelli Letizia , Cavallari Eugenio Nelson , Spagnolello Ornella , Silvestri Valeria , Vassalini Paolo , Scagnolari Carolina , Francone Marco , Mastroianni Claudio Maria , Carbone Iacopo
Published: November 2020

Background

People living with HIV (PLWH) are prone to develop sub-clinical Cardiovascular (CV) disease, despite the effectiveness of combined Antiretroviral Therapy (cART). Algorithms developed to predict CV risk in the general population could be inaccurate when applied to PLWH. Myocardial Extra-Cellular Matrix (ECM) expansion, measured by computed tomography, has been associated with an increased CV vulnerability in HIV-negative population. Measurement of Myocardial Extra-Cellular Volume (ECV) by computed tomography or magnetic resonance, is considered a useful surrogate for clinical evaluation of ECM expansion. In the present study, we aimed to determine the extent of cardiovascular involvement in asymptomatic HIV-infected patients with the use of a comprehensive cardiac computed tomography (CCT) approach.

Materials and methods

In the present study, ECV in low atherosclerotic CV risk PLWH was compared with ECV of age and gender matched HIV- individuals. 53 asymptomatic HIV + individuals (45 males, age 48 (42.5–48) years) on effective cART (CD4 + cell count: 450 cells/µL (IQR: 328–750); plasma HIV RNA: <37 copies/ml in all subjects) and 18 age and gender matched controls (14 males, age 55 (44.5–56) years) were retrospectively enrolled. All participants underwent CCT protocol to obtain native and postcontrast Hounsfield unit values of blood and myocardium, ECM was calculated accordingly.

Results

The ECV was significantly higher in HIV + patients than in the control group (ECV: 31% (IQR: 28%-31%) vs. 27.4% (IQR: 25%-28%), p < 0.001). The duration of cART (standardized β = 0.56 (0.33–0.95), p = 0.014) and the years of exposure to HIV infection (standardized β = 0.53 (0.4–0.92), p < 0.001), were positively and strongly associated with ECV values. Differences in ECV (p < 0.001) were also observed regarding the duration of cART exposure (< 5 years, 5–10 years and > 10 years). Moreover, ECV was independently associated with age of participants (standardized β = 0.42 (0.33–0.89), p = 0.084).

Conclusions

HIV infection and exposure to antiretrovirals play a detrimental role on ECV expansion. An increase in ECV indicates ECM expansion, which has been associated to a higher CV risk in the general population. The non-invasive evaluation of ECM trough ECV could represent an important tool to further understand the relationship between HIV infection, cardiac pathophysiology and the increased CV risk observed in PLWH.
Early surgical debridement and fixation for pyogenic lumbar spondylodiscitis
Authors: Refaat Mohamed Ibrahim , Abdallah Omar Y.
Published: November 2020

Background

Management of pyogenic lumbar spondylodiscitis still represent a major conflict and challenge in neurosurgery due to different pathogens and the different methods available for management.

Objective

The aim of this study was to evaluate the outcome of posterior lumbar spinal fixation with debridement as a treatment modality in the management of pyogenic lumbar spondylodiscitis.

Patients and method

This is a prospective study conducted on patients presenting to the Neurosurgery Department of Cairo University hospitals diagnosed to have either spontaneous or iatrogenic pyogenic lumbar spondylodiscitis. All cases were operated upon by surgical debridement, drainage, and posterior lumbar fixation in the same setting. Antibiotics were prescribed according to the obtained culture and sensitivity. Laboratory follow-up was done to all patients. Clinical outcome was evaluated in terms of the Denis Functional Pain Scale. Follow-up period ranged from 5 to 14 months.

Results

A total of 25 patients comprised of 15 males and 9 females with a mean age of 45.7 years (range 32–63 years) were included in this study. Nine cases had a previous lumbar discectomy surgery, and 15 cases presented with spontaneous spondylodiscitis. L4–5 level was the most frequent site of pyogenic discitis. Excellent outcome and good outcomes (score 1–3 in Denis Functional Pain Scale) were reported in 84% of the patients and poor outcomes (score 4–5) in 16%.

Conclusion

Surgical fixation and debridement can be considered as an effective modality in the management of pyogenic lumbar spondylodiscitis with early ambulation, good control of pain, and early hospital discharge.
“Dried Fruits”: Flaubert, Marx, and the Literary-Historical Event
Authors: Bray Patrick M.
Published: November 2020

This essay looks at Gustave Flaubert’s L’éducation sentimentale as a “literary-historical event,” that is, an event that becomes legible only by a literary text. Flaubert’s novel attempted to turn the ambiguous political events of 1848 and the coup d’état of Napoleon III into a literary manifesto and a history of his generation. One of the novel’s early titles was “Dried Fruits,” which conveys a sense of preserved youth or even lost potential that can be exploited later. Flaubert’s novel explores what changes over time and what inevitably repeats in apparently singular historical events. Similarly, Marx’s Eighteenth Brumaire of Louis Bonaparte famously uses literary and theatrical tropes to explain the same events as Flaubert as they unfolded. Both Flaubert and Marx show us that literary form (irony, farce, attention to linguistic repetition) participates in the politicization of, and the resistance to, historical events.
Genre Blindness in the New Descriptivism
Authors: Dean Tim
Published: November 2020

This essay considers the “descriptive turn” in literary studies from the vantage point of poetics, arguing that the history of Western poetry, from the Greeks to the present, offers through the category of epideixis a theory and practice of description that illuminates some of the methodological impasses of contemporary literary studies. Epideixis, a basic mode of pointing or linguistic ostension, confers value, often by way of praise or blame, without trying to persuade its audience with the practical immediacy of political or forensic rhetoric. Drawing on the ordinary language philosophy of Ludwig Wittgenstein and Stanley Cavell, the essay suggests that praise constitutes a philosophically rigorous alternative to critique. This argument is exemplified via the work of Mark Doty, a contemporary poet of description-as-praise.
Ολιστικές αντιλήψεις στην περιβαλλοντική ηθική
Authors: Μυώφα Άννα
Published: November 2020

Δεν διατίθεται περίληψη
Η αντίληψη του Αριστοτέλη για τη σοφία, τα χαρακτηριστικά της και η σύνδεση των αιτίων και των αρχών με τη σοφία και την επιστήμη κατά τον Αριστοτέλη
Authors: Θεοδούλου Αναστασία
Published: November 2020

Δεν διατίθεται περίληψη
Η μυστική θεολογία: ο Διονύσιος Αρεοπαγίτης και η σχέση του με τον νεοπλατωνισμό
Authors: Κοκοτσάκη Αρχόντισσα
Published: November 2020

Δεν διατίθεται περίληψη
Η επιχειρηματική ηθική ως μέσο επίτευξης βιώσιμης οικονομικής ανάπτυξης
Authors: Νικολαΐδου Άννα
Published: November 2020

Δεν διατίθεται περίληψη
UNA SECUENCIA DIDÁCTICA EN LA ENSEÑANZA DEL ÁLGEBRA LINEAL: MODELIZACIÓN Y UNIFICACIÓN DE COMPETENCIAS CON LA TRANSFORMACIÓN LINEAL
Authors: Pascual Pizarro Sara
Published: November 2020

Este trabajo contribuye, por un lado, a determinar las implicaciones didácticas de un análisis epistemológico sobre la generalidad de métodos económicos y análogos en la resolución de problemas de carácter lineal y, por otro lado, a construir y evaluar una secuencia didáctica que haga entender mejor por los estudiantes el significado de un concepto unificador y ayudar a la movilización espontánea de sus propiedades por la exposición a una serie de problemas que recurren a diferentes marcos matemáticos (numérico, geométrico, físico y analítico). La articulación teórica concierne a la Modelización y la Dualidad proceso/objeto en la formación del concepto. Nos inspiramos en una ingeniería didáctica para presentar una parte de los resultados de nuestra investigación. Estos resultados se refieren a los niveles de explicitación y a las competencias desarrolladas en el uso de las habilidades técnicas y métodos matemáticos que ayudan a explicitar el proceso de formación de la noción.
RECONSTRUCCIÓN DE SITUACIONES DIDÁCTICAS DE MATEMÁTICAS EN EL AULA. UN ESTUDIO EN PREESCOLAR
Authors: Laguna María , Block Sevilla David
Published: November 2020

El artículo se centra en las transformaciones que docentes imprimen a situaciones didácticas de matemáticas asociadas a un enfoque didáctico sociocontructivista. Se estudia el caso de dos educadoras trabajando con el tema de Tratamiento de la Información en preescolar. Metodológicamente, consideramos este estudio una Ingeniería Didáctica de Desarrollo (Perrin-Glorian, 2011). El análisis se realizó desde una doble perspectiva teórica: las situaciones didácticas se caracterizan y analizan desde la Teoría de las Situaciones Didácticas (Brousseau, 1998), mientras que, para el análisis de prácticas docentes se consideraron, principalmente, el doble enfoque didáctico/ergonómico (Rogalski y Robert, 2001) y la perspectiva etnográfica (Rockwell y Mercado, 2003). Si bien las transformaciones identificadas son distintas entre sí, en ambos casos se conservó lo esencial de los propósitos didácticos. Esto es expresivo de la necesidad y factibilidad de procesos de apropiación. El aporte principal del texto es la identificación de factores que subyacen a dichas transformaciones, de las necesidades a las que responden y de las tensiones que crean en la toma de decisiones en el aula.
Individualized Pricing for a Cloud Provider Hosting Interactive Applications
Authors: Jahandideh Hossein , Drew Julie Ward , Balestrieri Filippo , McCardle Kevin
Published: November 2020

We consider a cloud provider that hosts interactive applications, such as mobile apps and online games. Depending on the traffic of users for an application, the provider commits a subset of its resources (hardware capacity) to serve the application. The provider must choose a dynamic pricing mechanism to indirectly select the applications hosted and maximize revenue. We model the provider’s pricing problem as a large-scale stochastic dynamic program. To approach this problem, we propose a tractable approach to enable decomposing the multidimensional stochastic dynamic program into single-dimensional subproblems. We then extend the proposed framework to define an individualized dynamic pricing mechanism for the cloud provider. We present novel upper bounds on the optimal revenue to evaluate the performance of our pricing mechanism. The computational results show that a contract-based model of selling interactive cloud services achieves significantly greater revenue than the prevalent alternative and that our pricing scheme attains near-optimal revenue.
Help with making decisions
Authors: Hancock Dave
Published: November 2020

Arguably the thing you do most frequently and which is critical to the running of your practice is making decisions. Here, we look at the art and science of deciding and some tools that can help you choose wisely
Learning from patient safety incidents
Authors: Baylis Diane
Published: November 2020

Diane Baylis, Clinical Risk Educator at Medical Protection, explores how the practice team can help in creating a positive safety culture and avoid future incidents
Comparison of different in situ optical temperature probing techniques for cryogenic Yb:YLF
Authors: Demirbas Umit , Thesinga Jelto , Kellert Martin , Kärtner Franz X. , Pergament Mikhail
Published: November 2020

We present, what is to our knowledge, the first detailed set of experiments comparing different in situ optical temperature estimation methods for Yb:YLF (Yb:LiYF4) crystals used in cryogenic laser applications. The proposed temperature estimation methods are based on the temperature dependence of emission spectra of Yb:YLF in E//c axis, and looks at either the variation of the spectral intensity ratio of different wavelengths, or to the full-width half-maximum (FWHM) of the emission lines, or to the overall absolute integrated spectral change with respect to a reference temperature (also known as Differential Luminescence Thermometry: DLT). We have shown that by using the DLT method we can estimate the temperature of Yb:YLF crystals in the 78-300 K range with an accuracy better than ±1 K. The other methods work well in the 78-150 K range, and provide a fast temperature estimation with ±2 K accuracy. The benefit of the proposed technique has been demonstrated via evaluation of thermal contact quality of different Yb:YLF crystals, where we have seen that, a temperature estimation accuracy of ±5 K is feasible even for samples under nonhomogeneous thermal load. We hope the findings presented in this work to be useful to laser engineers and scientists working with cryogenic Yb:YLF systems.
Acetate and glycerol are not uniquely suited for the evolution of cross-feeding in E. coli
Authors: San Roman Magdalena , Wagner Andreas
Published: November 2020

The evolution of cross-feeding among individuals of the same species can help generate genetic and phenotypic diversity even in completely homogeneous environments. Cross-feeding Escherichia coli strains, where one strain feeds on a carbon source excreted by another strain, rapidly emerge during experimental evolution in a chemically minimal environment containing glucose as the sole carbon source. Genome-scale metabolic modeling predicts that cross-feeding of 58 carbon sources can emerge in the same environment, but only cross-feeding of acetate and glycerol has been experimentally observed. Here we use metabolic modeling to ask whether acetate and glycerol cross-feeding are especially likely to evolve, perhaps because they require less metabolic change, and thus perhaps also less genetic change than other cross-feeding interactions. However, this is not the case. The minimally required metabolic changes required for acetate and glycerol cross feeding affect dozens of chemical reactions, multiple biochemical pathways, as well as multiple operons or regulons. The complexity of these changes is consistent with experimental observations, where cross-feeding strains harbor multiple mutations. The required metabolic changes are also no less complex than those observed for multiple other of the 56 cross feeding interactions we study. We discuss possible reasons why only two cross-feeding interactions have been discovered during experimental evolution and argue that multiple new cross-feeding interactions may await discovery.
Fine-tuning autophagy maximises lifespan and is associated with changes in mitochondrial gene expression in Drosophila
Authors: Bjedov Ivana , Cochemé Helena M. , Foley Andrea , Wieser Daniela , Woodling Nathaniel S. , Castillo-Quan Jorge Iván , Norvaisas Povilas , Lujan Celia , Regan Jennifer C. , Toivonen Janne M. , Murphy Michael P. , Thornton Janet , Kinghorn Kerri J. , Neufeld Thomas P. , Cabreiro Filipe , Partridge Linda
Published: November 2020

Increased cellular degradation by autophagy is a feature of many interventions that delay ageing. We report here that increased autophagy is necessary for reduced insulin-like signalling (IIS) to extend lifespan in Drosophila and is sufficient on its own to increase lifespan. We first established that the well-characterised lifespan extension associated with deletion of the insulin receptor substrate chico was completely abrogated by downregulation of the essential autophagy gene Atg5. We next directly induced autophagy by over-expressing the major autophagy kinase Atg1 and found that a mild increase in autophagy extended lifespan. Interestingly, strong Atg1 up-regulation was detrimental to lifespan. Transcriptomic and metabolomic approaches identified specific signatures mediated by varying levels of autophagy in flies. Transcriptional upregulation of mitochondrial-related genes was the signature most specifically associated with mild Atg1 upregulation and extended lifespan, whereas short-lived flies, possessing strong Atg1 overexpression, showed reduced mitochondrial metabolism and up-regulated immune system pathways. Increased proteasomal activity and reduced triacylglycerol levels were features shared by both moderate and high Atg1 overexpression conditions. These contrasting effects of autophagy on ageing and differential metabolic profiles highlight the importance of fine-tuning autophagy levels to achieve optimal healthspan and disease prevention.
Runx2 is essential for the transdifferentiation of chondrocytes into osteoblasts
Authors: Qin Xin , Jiang Qing , Nagano Kenichi , Moriishi Takeshi , Miyazaki Toshihiro , Komori Hisato , Ito Kosei , Mark Klaus von der , Sakane Chiharu , Kaneko Hitomi , Komori Toshihisa
Published: November 2020

Chondrocytes proliferate and mature into hypertrophic chondrocytes. Vascular invasion into the cartilage occurs in the terminal hypertrophic chondrocyte layer, and terminal hypertrophic chondrocytes die by apoptosis or transdifferentiate into osteoblasts. Runx2 is essential for osteoblast differentiation and chondrocyte maturation. Runx2-deficient mice are composed of cartilaginous skeletons and lack the vascular invasion into the cartilage. However, the requirement of Runx2 in the vascular invasion into the cartilage, mechanism of chondrocyte transdifferentiation to osteoblasts, and its significance in bone development remain to be elucidated. To investigate these points, we generated Runx2fl/flCre mice, in which Runx2 was deleted in hypertrophic chondrocytes using Col10a1 Cre. Vascular invasion into the cartilage was similarly observed in Runx2fl/fl and Runx2fl/flCre mice. Vegfa expression was reduced in the terminal hypertrophic chondrocytes in Runx2fl/flCre mice, but Vegfa was strongly expressed in osteoblasts in the bone collar, suggesting that Vegfa expression in bone collar osteoblasts is sufficient for vascular invasion into the cartilage. The apoptosis of terminal hypertrophic chondrocytes was increased and their transdifferentiation was interrupted in Runx2fl/flCre mice, leading to lack of primary spongiosa and osteoblasts in the region at E16.5. The osteoblasts appeared in this region at E17.5 in the absence of transdifferentiation, and the number of osteoblasts and the formation of primary spongiosa, but not secondary spongiosa, reached to levels similar those in Runx2fl/fl mice at birth. The bone structure and volume and all bone histomophometric parameters were similar between Runx2fl/fl and Runx2fl/flCre mice after 6 weeks of age. These findings indicate that Runx2 expression in terminal hypertrophic chondrocytes is not required for vascular invasion into the cartilage, but is for their survival and transdifferentiation into osteoblasts, and that the transdifferentiation is necessary for trabecular bone formation in embryonic and neonatal stages, but not for acquiring normal bone structure and volume in young and adult mice.
Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda
Authors: Kitonsa Jonathan , Nsubuga Rebecca , Mayanja Yunia , Kiwanuka Julius , Nikweri Yofesi , Onyango Martin , Anywaine Zacchaeus , Ggayi Abu-Baker , Kibengo Freddie Mukasa , Kaleebu Pontiano , Day Jeremy
Published: November 2020

Globally, early initiation of antiretroviral therapy for HIV led to a reduction in the estimated mortality from cryptococcal meningitis (CCM) from 624,700 in 2009 to 181,100 in 2014. However, CCM remains one of the leading causes of mortality among HIV infected patients especially in sub-Saharan Africa where 75% of the deaths occur. Most of the studies evaluating mortality have reported short-term mortality (at or before 10 weeks of therapy). We determined mortality and associated factors among patients treated for CCM in the CryptoDex trial (ISRCTN59144167) in Uganda, and the effect of dexamethasone adjunctive therapy on mortality at two years. We conducted a retrospective cohort study between May 2017 and July 2017 to determine the long term survival (up to 2 years post-randomization) of all patients who had been enrolled into the CryptoDex trial in Uganda. The CryptoDex trial recruited between April 2013 and February 2015. We estimated mortality rates and determined factors affecting mortality at two years using Cox regression. The study followed up 211 participants, 127 (60.2%) of whom were male. Sixteen participants (7.58%) were diagnosed with HIV at the same admission when CCM was diagnosed. By two years following randomization 127 (60%) participants had died, a mortality rate of 67 deaths per 100 person-years. Mortality was associated with Glasgow coma score (GCS) below 15 (adjusted Hazard ratio (aHR) 1.77, 95% CI: 1.02–2.44), p = 0.040; weight (aHR 0.97, per 1 Kg increase; 95% CI: 0.94–0.99), p = 0.003; and presence of convulsions (aHR 2.31, 95% CI: 1.32–4.04), p = 0.004, while dexamethasone use and fungal burden had no effect. Long-term mortality in CCM patients remains high even among patients receiving recommended therapy. Strategies to improve long-term survival in CCM patients are urgently needed, especially targeting those with reduced GCS, low weight, and convulsions.
A community survey of coverage and adverse events following country-wide triple-drug mass drug administration for lymphatic filariasis elimination, Samoa 2018
Authors: Willis Gabriela A. , Mayfield Helen J. , Kearns Therese , Naseri Take , Thomsen Robert , Gass Katherine , Sheridan Sarah , Graves Patricia M. , Lau Colleen L.
Published: November 2020

The Global Programme to Eliminate Lymphatic Filariasis has made considerable progress but is experiencing challenges in meeting targets in some countries. Recent World Health Organization guidelines have recommended two rounds of triple-drug therapy with ivermectin, diethylcarbamazine (DEC), and albendazole (IDA), in areas where mass drug administration (MDA) results with two drugs (DEC and albendazole) have been suboptimal, as is the case in Samoa. In August 2018, Samoa was the first country in the world to implement countrywide triple-drug MDA. This paper aims to describe Samoa’s experience with program coverage and adverse events (AEs) in the first round of triple-drug MDA. We conducted a large cross-sectional community survey to assess MDA awareness, reach, compliance, coverage and AEs in September/October 2018, 7–11 weeks after the first round of triple-drug MDA. In our sample of 4420 people aged ≥2 years (2.2% of the population), age-adjusted estimates indicated that 89.0% of the eligible population were offered MDA, 83.9% of the eligible population took MDA (program coverage), and 80.2% of the total population took MDA (epidemiological coverage). Overall, 83.8% (2986/3563) reported that they did not feel unwell at all after taking MDA. Mild AEs (feeling unwell but able to do normal everyday things) were reported by 13.3% (476/3563) and moderate or severe AEs (feeling unwell and being unable to do normal everyday activities such as going to work or school) by 2.9% (103/3563) of participants. This study following the 2018 triple-drug MDA in Samoa demonstrated a high reported program awareness and reach of 90.8% and 89.0%, respectively. Age-adjusted program coverage of 83.9% of the total population showed that MDA was well accepted and well tolerated by the community.
Broad diversity of Mycobacterium tuberculosis complex strains isolated from humans and cattle in Northern Algeria suggests a zoonotic transmission cycle
Authors: Damene Hanane , Tahir Djamel , Diels Maren , Berber Ali , Sahraoui Naima , Rigouts Leen
Published: November 2020

Mycobacterium tuberculosis complex (MTBC) comprises closely related species responsible for human and animal tuberculosis (TB). Efficient species determination is useful for epidemiological purposes, especially for the elucidation of the zoonotic contribution. In Algeria, data on MTBC genotypes are largely unknown. In this study, we aimed to investigate the occurrence and diversity of MTBC genotypes causing human and bovine TB in Northern Algeria. During a two-year sampling period (2017–2019) in two regions of Northern Algeria, we observed an overall prevalence of 6.5% of tuberculosis (TB) among slaughtered cattle, which is higher than previous Algerian data yet comparable to neighboring countries. A total of 296 Mycobacterium tuberculosis complex (MTBC) isolates were genotyped by spoligotyping: 181 from tissues with TB-like lesions collected from 181 cattle carcasses and 115 from TB patients. In human isolates, we identified 107 M. tuberculosis, seven M. bovis and one “M. pinnipedii-like”, while for bovine samples, 174 isolates were identified as M. bovis, three as M. caprae, three as “M. pinnipedii-like” and one as “M. microti-like”. The majority of isolates (89.2%) belonged to 72 different known Shared International Types (SIT) or M. bovis spoligotypes (SB), while we also identified seven new SB profiles (SB2695 to SB2701). Twenty-eight of the SB profiles were new to Algeria. Our data suggest zoonotic transmission in Sétif, where significantly more TB was observed among cattle (20%) compared to the slaughterhouses from the three other regions (5.4%–7.3%) (p < 0.0001), with the isolation of the same M. bovis genotypes from TB patients. The present study showed a high genetic diversity of MTBC isolated from human and cattle in Northern Algeria. Even though relatively small in terms of numbers, our data suggest the zoonotic transmission of TB from cattle to humans, suggesting the need for stronger eradication strategies for bovine TB.
Analysis of mutations of defensin protein using accelerated molecular dynamics simulations
Authors: Pandey Bharati , Tyagi Chetna , Prajapati Gopal Kumar , Mishra Awdhesh Kumar , Hashem Abeer , Alqarawi Abdulaziz A. , Abd_Allah Elsayed Fathi , Mohanta Tapan Kumar
Published: November 2020

Plant defensins possess diverse biological functions that include antifungal and antibacterial activities and α-amylase and trypsin inhibitory properties. Two mutations, G9R and V39R, were confirmed to increase the antifungal activity ofRaphanus sativusantifungal protein 2 (RsAFP2). Accelerated Molecular Dynamics (aMD) were carried out to examine the conformational changes present in these RsAFP2 mutants, and its two closest homologs compared to the wild-type protein. Specifically, the root mean square fluctuation values for the eight cysteine amino acids involved in the four disulfide bonds were low in the V39R mutant compared to the wild-type. Additionally, analysis of the free energy change revealed that G9R and V39R mutations exert a neutral and stabilizing effect on RsAFP2 conformation, and this is supported by the observed lower total energy of mutants compared to the wild-type, suggesting that enhanced stability of the mutants. However, MD simulations to a longer time scale would aid in capturing more conformational state of the wild-type and mutants defensin protein. Furthermore, the aMD simulations on fungal mimic membranes with RsAFP2 and its mutants and homologs showed that the mutant proteins caused higher deformation and water diffusion than the native RsAFP2, especially the V39R mutant. The mutant variants seem to interact by specifically targeting the POPC and POPI lipids amongst others. This work highlights the stabilizing effect of mutations at the 9thand 39thpositions of RsAFP2 and their increased membrane deformation activity.
Inventive nesting behaviour in the keyhole wasp Pachodynerus nasidens Latreille (Hymenoptera: Vespidae) in Australia, and the risk to aviation safety
Authors: House Alan P. N. , Ring Jackson G. , Shaw Phillip P.
Published: November 2020

The keyhole wasp (Pachodynerus nasidensLatreille 1812), a mud-nesting wasp native to South and Central America and the Caribbean, is a relatively recent (2010) arrival in Australia. In its native range it is known to use man-made cavities to construct nests. A series of serious safety incidents Brisbane Airport related to the obstruction of vital airspeed measuring pitot probes on aircraft possibly caused by mud-nesting wasps, prompted an assessment of risk. An experiment was designed to determine the species responsible, the types of aircraft most affected, the seasonal pattern of potential risk and the spatial distribution of risk on the airport. A series of replica pitot probes were constructed using 3D-printing technology, representing aircraft with high numbers of movements (landings and take-offs), and mounted at four locations at the airport. Probes were monitored for 39 months. Probes blocked by mud nesting wasps were retrieved and incubated in mesh bags. Emerging wasps were identified to species. Results show that all nests in probes were made byP.nasidens, and peak nesting occurs in the summer months. Nesting success (as proportion of nests with live adult emergents) was optimal between 24 and 31°C and that probes with apertures of more than 3 mm diameter are preferred. Not all areas on the airport are affected equally, with the majority of nests constructed in one area. The proportion of grassed areas within 1000 m of probes was a significant predictor of nesting, and probe volume may determine the sex of emerging wasps.
A novel method for detecting extra-home range movements (EHRMs) by animals and recommendations for future EHRM studies
Authors: Jacobsen Todd C. , Wiskirchen Kevyn H. , Ditchkoff Stephen S.
Published: November 2020

Infrequent, long-distance animal movements outside of typical home range areas provide useful insights into resource acquisition, gene flow, and disease transmission within the fields of conservation and wildlife management, yet understanding of these movements is still limited across taxa. To detect these extra-home range movements (EHRMs) in spatial relocation datasets, most previous studies compare relocation points against fixed spatial and temporal bounds, typified by seasonal home ranges (referred to here as the “Fixed-Period” method). However, utilizing home ranges modelled over fixed time periods to detect EHRMs within those periods likely results in many EHRMs going undocumented, particularly when an animal’s space use changes within that period of time. To address this, we propose a novel, “Moving-Window” method of detecting EHRMs through an iterative process, comparing each day’s relocation data to the preceding period of space use only. We compared the number and characteristics of EHRM detections by both the Moving-Window and Fixed-Period methods using GPS relocations from 33 white-tailed deer (Odocoileus virginianus) in Alabama, USA. The Moving-Window method detected 1.5 times as many EHRMs as the Fixed-Period method and identified 120 unique movements that were undetected by the Fixed-Period method, including some movements that extended nearly 5 km outside of home range boundaries. Additionally, we utilized our EHRM dataset to highlight and evaluate potential sources of variation in EHRM summary statistics stemming from differences in definition criteria among previous EHRM literature. We found that this spectrum of criteria identified between 15.6% and 100.0% of the EHRMs within our dataset. We conclude that variability in terminology and definition criteria previously used for EHRM detection hinders useful comparisons between studies. The Moving-Window approach to EHRM detection introduced here, along with proposed methodology guidelines for future EHRM studies, should allow researchers to better investigate and understand these behaviors across a variety of taxa.
Feasibility of fresh frozen human cadavers as a research and training model for endovascular image guided interventions
Authors: Jansen Marloes M. , Hazenberg Constantijn E. V. B. , de Ruiter Quirina M. B. , van Hamersvelt Robbert W. , Bleys Ronald L. A. W. , van Herwaarden Joost A.
Published: November 2020

Objective

To describe the feasibility of a fresh frozen human cadaver model for research and training of endovascular image guided procedures in the aorta and lower extremity.

Methods

The cadaver model was constructed in fresh frozen human cadaver torsos and lower extremities. Endovascular access was acquired by inserting a sheath in the femoral artery. The arterial segment of the specimen was restricted by ligation of collateral arteries and, in the torsos, clamping of the contralateral femoral artery and balloon occlusion of the supratruncal aorta. Tap water was administered through the sheath to create sufficient intraluminal pressure to manipulate devices and acquire digital subtraction angiography (DSA). Endovascular cannulation tasks of the visceral arteries (torso) or the peripheral arteries (lower extremities) were performed to assess the vascular patency of the model. Feasibility of this model is based on our institute’s experiences throughout the use of six fresh frozen human cadaver torsos and 22 lower extremities.

Results

Endovascular simulation in the aortic and peripheral vasculature was achieved using this human cadaver model. Acquisition of DSA images was feasible in both the torsos and the lower extremities. Approximately 84 of the 90 target vessels (93.3%) were patent, the remaining six vessels showed signs of calcified steno-occlusive disease.

Conclusions

Fresh frozen human cadavers provide a feasible simulation model for aortic and peripheral endovascular interventions, and can potentially reduce the need for animal experimentation. This model is suitable for the evaluation of new endovascular devices and techniques or to master endovascular skills.
Psychological trauma in different mechanisms of traumatic injury: A hospital-based cross-sectional study
Authors: Agarwal Tulika Mehta , Muneer Mohammed , Asim Mohammad , Awad Malaz , Afzal Yousra , Al-Thani Hassan , Alhassan Ahmed , Mollazehi Monira , El-Menyar Ayman
Published: November 2020

Background

Psychological distress following traumatic injury can influence the patient health, well-being and quality of life; however, this impact may partly vary according to the type and severity of injury. We aimed to study the predominant distress causing cluster and individual symptoms of Post-Traumatic Stress Disorders (PTSD) at the clinical and subthreshold level in patients with traumatic injuries, based on the mechanism of injury (MOI).

Methods

A hospital based cross-sectional study was conducted at a Level 1 Trauma Center utilizing PTSD Checklist to diagnose PTSD after one month of the traumatic event. All patients suffering from psychological distresses were assessed by a clinical psychologist in the trauma section. PTSD diagnostic criteria from DSM-5 were used to classify the patients. The inclusion criteria comprised of adult trauma patients who were directly involved in traumatic injuries and admitted under the Trauma Surgery services for a minimum of one day; have ability to provide written informed consent and can be assessed with the PCL-5 checklist after 4 weeks post-injury.

Results

Two hundred patients completed PCL-5 checklist, of them 26 (13.0%) were positive for PTSD and 174 (87%) had subthreshold scores. The mean age of participants was 34.4±11.8 years and males constituted 90.5%. Road traffic injury (RTI) was most the frequent injury mechanism (59%). PTSD positive patients with RTI, fall of heavy objects, pedestrian injury and assaults had highest average scores on clusters of negative alterations in mood and cognitions (16.9, 18.0, 18.5, 17.0 respectively), followed by hyperarousal. Symptom of always being on the guard and having repeated unwanted or disturbing memories of the incident, was reported by nearly 100% PTSD positive patients. Patients with subthreshold scores also reported distressing symptoms on all four clusters of PTSD.

Conclusions

Patients with different MOI showed a broad range of psychological problems with respect to symptom clusters. Negative alteration in mood and cognition followed by hyperarousal caused higher level of distress in patients post traumatic injuries. Subthreshold symptoms of PTSD are more common and deserve more attention.