bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antagonizing the spindle assembly checkpoint silencing enhances paclitaxel and Navitoclax-mediated apoptosis with distinct mechanistic
Authors: Henriques Ana C. , Silva Patrícia M. A. , Sarmento Bruno , Bousbaa Hassan 
Published: February 2021

AbstractAntimitotic drugs arrest cells in mitosis through chronic activation of the spindle assembly checkpoint (SAC), leading to cell death. However, drug-treated cancer cells can escape death by undergoing mitotic slippage, due to premature mitotic exit. Therefore, overcoming slippage issue is a promising chemotherapeutic strategy to improve the effectiveness of antimitotics. Here, we antagonized SAC silencing by knocking down the MAD2-binding protein p31comet, to delay mitotic slippage, and tracked cancer cells treated with the antimitotic drug paclitaxel, over 3 days live-cell time-lapse analysis. We found that in the absence of p31comet, the duration of mitotic block was increased in cells challenged with nanomolar concentrations of paclitaxel, leading to an additive effects in terms of cell death which was predominantly anticipated during the first mitosis. As accumulation of an apoptotic signal was suggested to prevent mitotic slippage, when we challenged p31comet-depleted mitotic-arrested cells with the apoptosis potentiator Navitoclax (previously called ABT-263), cell fate was shifted to accelerated post-mitotic death. We conclude that inhibition of SAC silencing is critical for enhancing the lethality of antimitotic drugs as well as that of therapeutic apoptosis-inducing small molecules, with distinct mechanisms. The study highlights the potential of p31comet as a target for antimitotic therapies.
Conservation priorities in an endangered estuarine seahorse are informed by demographic history
Authors: Mkare Thomas Kalama , Jansen van Vuuren Bettine , Teske Peter R. 
Published: February 2021

AbstractHistorical demographic events shape genetic diversity that remains evident in the genomes of contemporary populations. In the case of species that are of conservation concern, this information helps to unravel evolutionary histories that can be critical in guiding conservation efforts. The Knysna seahorse, Hippocampus capensis, is the world’s most endangered seahorse species, and it presently survives in only three estuaries on the South African south coast. Factors that contributed to the species becoming endangered are unclear; additionally, the lack of information on whether the three populations should be managed separately because of potential long-term isolation hampers effective management efforts. In the present study, we reconstructed the seahorses’ demographic history using a suite of microsatellite loci. We found that the largest population (Knysna Estuary) has colonised the other estuaries relatively recently (< 450 years ago), and that its population size is comparatively large and stable. Neither of the other two populations shows signs of long-term reductions in population size. The high conservation status of the species is thus a result of its limited range rather than historical population declines. Our findings indicate that the long-term survival of H. capensis depends primarily on the successful management of the Knysna population, although the other estuaries may serve as reservoirs of genetic diversity.
Sophisticated viral quasispecies with a genotype-related pattern of mutations in the hepatitis B X gene of HBeAg-ve chronically infected patients
Authors: Cortese Maria Francesca , González Carolina , Gregori Josep , Casillas Rosario , Carioti Luca , Guerrero-Murillo Mercedes , Riveiro-Barciela Mar , Godoy Cristina , Sopena Sara , Yll Marçal , Quer Josep , Rando Ariadna , Lopez-Martinez Rosa , Pacín Ruiz Beatriz , García-García Selene , Esteban-Mur Rafael , Tabernero David , Buti Maria , Rodríguez-Frías Francisco 
Published: February 2021

AbstractPatients with HBeAg-negative chronic infection (CI) have not been extensively studied because of low viremia. The HBx protein, encoded by HBX, has a key role in viral replication. Here, we analyzed the viral quasispecies at the 5′ end of HBX in CI patients and compared it with that of patients in other clinical stages. Fifty-eight HBeAg-negative patients were included: 16 CI, 19 chronic hepatitis B, 16 hepatocellular carcinoma and 6 liver cirrhosis. Quasispecies complexity and conservation were determined in the region between nucleotides 1255 and 1611. Amino acid changes detected were tested in vitro. CI patients showed higher complexity in terms of mutation frequency and nucleotide diversity and higher quasispecies conservation (p < 0.05). A genotype D-specific pattern of mutations (A12S/P33S/P46S/T36D-G) was identified in CI (median frequency, 81.7%), which determined a reduction in HBV DNA release of up to 1.5 log in vitro. CI patients showed a more complex and conserved viral quasispecies than the other groups. The genotype-specific pattern of mutations could partially explain the low viremia observed in these patients.
Early risk assessment for COVID-19 patients from emergency department data using machine learning
Authors: Heldt Frank S. , Vizcaychipi Marcela P. , Peacock Sophie , Cinelli Mattia , McLachlan Lachlan , Andreotti Fernando , Jovanović Stojan , Dürichen Robert , Lipunova Nadezda , Fletcher Robert A. , Hancock Anne , McCarthy Alex , Pointon Richard A. , Brown Alexander , Eaton James , Liddi Roberto , Mackillop Lucy , Tarassenko Lionel , Khan Rabia T. 
Published: February 2021

AbstractSince its emergence in late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with more than 55 million reported cases and 1.3 million estimated deaths worldwide. While epidemiological and clinical characteristics of COVID-19 have been reported, risk factors underlying the transition from mild to severe disease among patients remain poorly understood. In this retrospective study, we analysed data of 879 confirmed SARS-CoV-2 positive patients admitted to a two-site NHS Trust hospital in London, England, between January 1st and May 26th, 2020, with a majority of cases occurring in March and April. We extracted anonymised demographic data, physiological clinical variables and laboratory results from electronic healthcare records (EHR) and applied multivariate logistic regression, random forest and extreme gradient boosted trees. To evaluate the potential for early risk assessment, we used data available during patients’ initial presentation at the emergency department (ED) to predict deterioration to one of three clinical endpoints in the remainder of the hospital stay: admission to intensive care, need for invasive mechanical ventilation and in-hospital mortality. Based on the trained models, we extracted the most informative clinical features in determining these patient trajectories. Considering our inclusion criteria, we have identified 129 of 879 (15%) patients that required intensive care, 62 of 878 (7%) patients needing mechanical ventilation, and 193 of 619 (31%) cases of in-hospital mortality. Our models learned successfully from early clinical data and predicted clinical endpoints with high accuracy, the best model achieving area under the receiver operating characteristic (AUC-ROC) scores of 0.76 to 0.87 (F1 scores of 0.42–0.60). Younger patient age was associated with an increased risk of receiving intensive care and ventilation, but lower risk of mortality. Clinical indicators of a patient’s oxygen supply and selected laboratory results, such as blood lactate and creatinine levels, were most predictive of COVID-19 patient trajectories. Among COVID-19 patients machine learning can aid in the early identification of those with a poor prognosis, using EHR data collected during a patient’s first presentation at ED. Patient age and measures of oxygenation status during ED stay are primary indicators of poor patient outcomes.
The preparation and application of calcium phosphate biomedical composites in filling of weight-bearing bone defects
Authors: Cheng Lijia , Lin Tianchang , Khalaf Ahmad Taha , Zhang Yamei , He Hongyan , Yang Liming , Yan Shuo , Zhu Jiang , Shi Zheng 
Published: February 2021

AbstractNowadays, artificial bone materials have been widely applied in the filling of non-weight bearing bone defects, but scarcely ever in weight-bearing bone defects. This study aims to develop an artificial bone with excellent mechanical properties and good osteogenic capability. Firstly, the collagen-thermosensitive hydrogel-calcium phosphate (CTC) composites were prepared as follows: dissolving thermosensitive hydrogel at 4 °C, then mixing with type I collagen as well as tricalcium phosphate (CaP) powder, and moulding the composites at 37 °C. Next, the CTC composites were subjected to evaluate for their chemical composition, micro morphology, pore size, Shore durometer, porosity and water absorption ability. Following this, the CTC composites were implanted into the muscle of mice while the 70% hydroxyapatite/30% β-tricalcium phosphate (HA/TCP) biomaterials were set as the control group; 8 weeks later, the osteoinductive abilities of biomaterials were detected by histological staining. Finally, the CTC and HA/TCP biomaterials were used to fill the large segments of tibia defects in mice. The bone repairing and load-bearing abilities of materials were evaluated by histological staining, X-ray and micro-CT at week 8. Both the CTC and HA/TCP biomaterials could induce ectopic bone formation in mice; however, the CTC composites tended to produce larger areas of bone and bone marrow tissues than HA/TCP. Simultaneously, bone-repairing experiments showed that HA/TCP biomaterials were easily crushed or pushed out by new bone growth as the material has a poor hardness. In comparison, the CTC composites could be replaced gradually by newly formed bone and repair larger segments of bone defects. The CTC composites trialled in this study have better mechanical properties, osteoinductivity and weight-bearing capacity than HA/TCP. The CTC composites provide an experimental foundation for the synthesis of artificial bone and a new option for orthopedic patients.
ANN design of multiple open‐switch fault diagnosis for three‐phase PWM converters
Authors: Kim Won‐Jae , Kim Sang‐Hoon 
Published: February 2021

In this paper, Artificial Neural Networks (ANNs) for diagnosing multiple open‐switch faults in three‐phase PWM (Pulse Width Modulation) converters are designed. For single and double open‐switch faults in the converters, there are 21 types of fault modes, causing distorted phase currents. Since these abnormal currents can induce secondary faults in peripherals, the open‐fault diagnosis is essentially required. In this paper, a two‐step technique based on ANNs is utilized for the diagnosis of the multiple open‐switch fault. First, dc and harmonic components of the currents are extracted by using an ADALINE (Adaptive Linear Neuron). In the first step, the ANN categorizes fault modes into six sectors by using dc components in the three‐phase plane. In the second step, the ANN localizes fault modes by using dc components and the ratio of d–q axes currents THDs (Total Harmonics Distortions) in each sector. Especially, both switches open‐faults in the same legs are localised by counting the sampled zero current of the fault currents. The proposed two‐step technique allows a simple design of the ANNs for the diagnosis, and a short execution time about 22 s. Simulations and experiments for a 3.7 kW three‐phase PWM converter confirmed the validity of the proposed diagnostic method.
Signalised intersection control in a connected vehicle environment: User throughput maximisation strategy
Authors: Mohammadi Roozbeh , Roncoli Claudio , Mladenović Miloš N. 
Published: February 2021

AbstractConnected vehicle (CV) technology is expected to bring additional opportunities to share, collect, and exploit various information on vehicles and their occupants. Assuming that CVs are able to transmit on‐board users and vehicle data, a user‐based signal timing optimisation (UBSTO) strategy is proposed, designed to optimise user throughput for signalised intersections. In the CV environment, the inputs of the proposed algorithm consist of position and speed of CVs, as well as the number of passengers travelling in each vehicle, while the output is the optimum green time duration for each signal phase. In addition, authors' proposed strategy is able to adapt the cycle length to the traffic volume condition. In case of missing users data, the same strategy can also operate in vehicle‐based mode, where the objective is vehicle‐throughput maximization. The performance of the proposed strategy is compared with a fully actuated controller (FAC) in microscopic simulation, for several scenarios, including different CV penetration rates. Authors' findings show that UBSTO can effectively increase user throughput and decrease average user delay in comparison with FAC, while also prioritising vehicles with higher number of users on‐board. These findings have implications for further development of prioritization strategies for public transport and ride‐sharing vehicles.
Histologic Findings of Choroidal Vasculopathy in Eyes Enucleated following Radiation Therapy for Uveal Melanoma: Radiation Choroidopathy
Authors: Platt Sean , Salomao Diva R. , Pulido Jose 
Published: February 2021

Abstract
Introduction Little has been published about the choroidal vascular changes that occur years after radiation exposure. The aim of this study was to review the histological changes observed in the choroidal vasculature following radiotherapy for uveal melanoma.
Methods Records from a single institution were retrospectively reviewed from June 7, 2007 to June 7, 2017; 101 patients with a diagnosis of uveal melanoma that underwent enucleation had their records reviewed. Out of these, a total of 26 eyes had undergone plaque brachytherapy prior to enucleation, which had been performed at a mean time of 7.2 years (range from 0 years to 30 years) after the initial plaque placement. A histopathologic analysis was conducted on all 26 eyes with special emphasis on the choroidal changes. Of these 26 eyes, 18 demonstrated evidence of radiation-induced vasculopathy.
Results Of the 18 eyes, 10/18 (55%) had radiation retinopathy and 16/18 (89%) had radiation choroidal vasculopathy. One patient had a phthisical eye, and the choroid could not be evaluated because the characteristics of the vasculature could not be determined. Nine cases had vitreous hemorrhage (50%), all cases had radiation retinopathy, and 8/9 (89%) had radiation choroidopathy. Of the 16 cases with radiation choroidal vasculopathy, 3/16 (19%) had only intratumoral radiation choroidal vasculopathy, 3/16 (19%) had only extratumoral radiation choroidal vasculopathy, and, thus, 10/16 (32%) had both intratumoral and extratumoral radiation choroidal vasculopathy. In patients with radiation choroidal vasculopathy, 2/16 (13%) had hyalinization of the choroidal vessels. Another 3/16 (19%) cases with radiation choroidal vasculopathy had ectatic vessels. The other 11/16 (68%) had evidence of both hyalinization of the choroidal vessels as well as ectatic vessels in the
choroid. Histological evidence of radiation retinopathy and choroidopathy were seen in 69% of eyes enucleated after receiving radiation therapy, which, in some cases, also had vitreous hemorrhage. Polypoidal choroidal vasculopathy, choroidal neovascularization, and retinal choroidal anastomoses (RAP-type lesions) were seen in 12 of the 16 eyes (75%).
Discussion/Conclusion Irradiation of malignant tumors of the eye causes not only radiation retinopathy but also radiation choroidopathy. The role of radiation choroidopathy in the subsequent visual loss following radiotherapy and the role of anti-VEGF therapy needs to be recognized and distinguished from radiation retinopathy. Our data adds to the prior limited knowledge that radiation affects the choroid and can induce specific phenotypes similar to the clinical spectrum of CNV, PCV, and RAP.
High sensitivity of ROSE-supported ERCP-guided brushing for biliary strictures
Authors: Archibugi Livia , Mariani Alberto , Ciambriello Biagio , Petrone Maria Chiara , Rossi Gemma , Testoni Sabrina Gloria Giulia , Carlucci Michele , Aldrighetti Luca , Falconi Massimo , Balzano Gianpaolo , Doglioni Claudio , Capurso Gabriele , Arcidiacono Paolo Giorgio 
Published: February 2021

Abstract
Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) plays a major role in biliary strictures, with brushing being a cheap and fast method to acquire a cytological specimen, despite a sensitivity around 45 %. Rapid on-site evaluation (ROSE) is widely used for endoscopic ultrasound-acquired cytological specimen adequacy, improving its sensitivity and specificity. Nevertheless, no study has evaluated its role for ERCP-guided brushing. Our aim was to assess the diagnostic yield of ERCP-guided brushing of biliary strictures when supported by ROSE.
Patients and methods This was a retrospective single-center study that included patients undergoing ERCP-guided brush cytology supported by ROSE for biliary strictures. Recorded data included patient clinical-radiological and ERCP features. Final diagnosis was determined after surgery, intraductal biopsy or adequate follow-up. The diagnostic yield was calculated and a subgroup analysis for factors associated with false-negative or true-positive results was performed.
Results Two hundred six patients were included, 57.3 % males, median age 72 years, 77.2 % having extrahepatic biliary strictures. Of the patients, 99 % had an adequate sample at ROSE after a mean of 2.6 passages. The diagnostic yield was accuracy 83 %, sensitivity 74.6 %, and specificity 98 %, positive and negative predictive values 98 % and 71 % respectively, with an area under the curve of 0.86. A diagnosis of cholangiocarcinoma was significantly more frequent among true-positive cases (68 % vs 46.8 %; P = 0.04).
Conclusions This is the first study evaluating the use of ROSE as support for ERCP-guided brushing of biliary strictures, with a sensitivity far higher than those reported for brushing alone and at least comparable to those of more expensive and invasive techniques.
Yamamoto Neue Schädelakupunktur YNSA
Authors: Ogal Hans P. 
Published: February 2021

ZusammenfassungDie Behandlung von Schmerzsymptomen und Einschränkungen des Bewegungssystems sind eine Domäne der Yamamoto Neue Schädelakupunktur (YNSA).Der Autor stellt, aufbauend auf seinem 2018 erschienenen Artikel zu den Grundlagen der YNSA, bewährte Punkte bei Beschwerden des Bewegungsapparats vor. Ein Fall aus der Praxis zeigt beispielhaft das Vorgehen und die möglichen Erfolge.
Serum Selenium Levels in Glaucoma: a Pilot Study
Authors: Lucio Marianna , Fick Alexander , Michalke Bernhard , Laemmer Robert , Hosari Sami , Hohberger Bettina 
Published: February 2021

Abstract
Background Trace elements are assumed to be involved in glaucoma pathogenesis via changes in oxidative stress. Especially serum selenium (Se) has been linked to this
neurodegenerative disease. Serum Se levels differ between countries due to nutrition and ethnicity. It was the aim of the present study to investigate serum Se levels in primary open-angle
glaucoma (POAG) patients and controls in Germany and to consider potential age and gender effects.
Material and Methods The Se concentration of 39 serum samples (22 patients with POAG, 17 controls) were analyzed by inductively coupled plasma-sector field mass spectrometry
(ICP-sf-MS) in high resolution mode. Covariance and percentile regression were analyzed. Age and gender were defined as confounding factors and their different trends were investigated.
Moreover, age was examined across different quantiles of Se levels.
Results Total serum least-squares means (LS-means) Se levels were 132.02 µg/L (controls) and 134.86 µg/L (POAG). Total serum Se levels did not differ between the study groups
(p > 0.05). Significant age and gender effects of serum Se were observed. Quantile analysis showed that the 1st serum Se quantile decreased with increasing age in POAG patients in
contrast to controls. The odds ratios of the 1st serum Se were 1.3 (with 2nd quantile) and 1.3 (with 3rd quantile), respectively.
Conclusion The serum Se level of the German cohort was almost half of those of the published US cohort (glaucoma 209.11 ng/mL; control 194.45 ng/mL). Age and gender effects were
observed; the serum Se level increased with age in women (controls and POAG), however, Se levels decreased with age in men (controls and POAG).
Gelenkbeschwerden homöopathisch behandeln
Authors: Boeddrich Ute 
Published: February 2021

ZusammenfassungIn diesem Artikel sollen von Arthritis bis Osteoporose einige bewährte Indikationen mit homöopathischen Mitteln bei häufigen Gelenkbeschwerden beschrieben werden. Entsprechende Leitsymptome und Modalitäten führen zu den passenden Medikamenten. Erwähnt werden auch einige sinnvolle andere bekannte Maßnahmen, die Erleichterung bringen können, ebenso pflanzliche Hilfen, Vitamine und orthomolekulare Substanzen.
Use of suction during endoscopic ultrasound-guided fine needle biopsy of solid pancreatic lesions with a Franseen-tip needle: a pilot comparative trial
Authors: Costa-Moreira Pedro , Vilas-Boas Filipe , Martins Diana , Moutinho-Ribeiro Pedro , Lopes Susana , Lopes Joanne , Barroca Helena , Macedo Guilherme 
Published: February 2021

Abstract
Background and study aims The utility of suction during endoscopic ultrasound (EUS) fine-needle biopsy (FNB) using Franseen-tip needle remains unclear and has not been evaluated in randomized trials. We designed a randomized crossover trial to compare the diagnostic yield during EUS-FNB using a 22G Franseen-tip needle, with and without standard suction.
Patients and methods Consecutive patients undergoing EUS-guided sampling of solid pancreatic lesions were recruited. A minimum of two passes were performed for each case: one with 20-mL syringe suction (S+) and another without (S–). The order of passes was randomized and the pathologist blinded. The endpoints were the diagnostic yield and the impact of blood contamination in the diagnosis.
Results Fifty consecutive patients were enrolled. The overall diagnostic accuracy was 84 %. A diagnosis of malignancy was obtained in 70 samples: 36 in the S+group and 34 in the S–group. A statistically significant difference was seen in the diagnostic accuracy (S+: 78 % vs. S–: 72 %, P < 0.01) and blood contamination (S+: 68 %; S–: 44 %, P < 0.01). The sensitivity, specificity, negative likelihood ratio and positive likelihood ratio for S+vs. S–samples were 76.6 % vs. 73.9 %, 100 % vs. 100 % and 0.23 vs. 0.26, NA vs NA, respectively. A negative impact of blood contamination in the overall diagnostic yield wasn’t seen, even in samples where suction was used (OR 0.36, P = 0.15)
Conclusions We found a higher diagnostic yield with the use of suction. It was associated with a higher degree of sample blood contamination that did not affect the diagnostic performance.