bluuebunny/crossref_metadata_2025 huggingface dataset:
General practitioners’ approaches to prostate-specific antigen testing in the north-east of the Netherlands
Authors: Kappen Sanny , Koops Lisa , Jürgens Verena , Freitag Michael H. , Blanker Marco H. , Timmer Antje , de Bock Geertruida H.
Published: December 2020

Background

There is wide variation in clinical practice for the early detection of prostate cancer, not least because of the ongoing debate about the benefits of prostate-specific antigen (PSA) testing. In this study, we aimed to assess the approaches, attitudes, and knowledge of general practitioners (GPs) regarding PSA testing in primary care in the Netherlands, particularly regarding recommendations for prostate cancer.

Methods

Questionnaire surveys were sent to 179 GPs in the north-east of the Netherlands, of which 65 (36%) were completed and returned. We also surveyed 23 GPs attending a postgraduate train-the-trainer day (100%). In addition to demographic data and practice characteristics, the 31-item questionnaire covered the attitudes, clinical practice, adherence to PSA screening recommendations, and knowledge concerning the recommendations for prostate cancer early detection. Statistical analysis was limited to the descriptive level.

Results

Most GPs (95%; n = 82) stated that they had at least read the Dutch GP guideline, but just half (50%; n = 43) also stated that they knew the content. Almost half (46%; n = 39) stated they would offer detailed counseling before ordering a PSA test to an asymptomatic man requesting a test. Overall, prostate cancer screening was reported to be of minor importance compared to other types of cancer screening.

Conclusions

Clinical PSA testing in primary care in this region of the Netherlands seems generally to be consistent with the relevant guideline for Dutch GPs that is restrictive to PSA testing. The next step will be to further evaluate the effects of the several PSA testing strategies.
The protective role of intracellular glutathione in Saccharomyces cerevisiae during lignocellulosic ethanol production
Authors: Raghavendran Vijayendran , Marx Christian , Olsson Lisbeth , Bettiga Maurizio
Published: December 2020

To enhance the competitiveness of industrial lignocellulose ethanol production, robust enzymes and cell factories are vital. Lignocellulose derived streams contain a cocktail of inhibitors that drain the cell of its redox power and ATP, leading to a decrease in overall ethanol productivity. Many studies have attempted to address this issue, and we have shown that increasing the glutathione (GSH) content in yeasts confers tolerance towards lignocellulose inhibitors, subsequently increasing the ethanol titres. However, GSH levels in yeast are limited by feedback inhibition of GSH biosynthesis. Multidomain and dual functional enzymes exist in several bacterial genera and they catalyse the GSH biosynthesis in a single step without the feedback inhibition. To test if even higher intracellular glutathione levels could be achieved and if this might lead to increased tolerance, we overexpressed the genes from two bacterial genera and assessed the recombinants in simultaneous saccharification and fermentation (SSF) with steam pretreated spruce hydrolysate containing 10% solids. Although overexpressing the heterologous genes led to a sixfold increase in maximum glutathione content (18 µmol gdrycellmass−1) compared to the control strain, this only led to a threefold increase in final ethanol titres (8.5 g L− 1). As our work does not conclusively indicate the cause-effect of increased GSH levels towards ethanol titres, we cautiously conclude that there is a limit to cellular fitness that could be accomplished via increased levels of glutathione.
Comparison of Precision and Accuracy of Five Methods to Analyse Total Score Data
Authors: Wellhagen Gustaf J. , Karlsson Mats O. , Kjellsson Maria C.
Published: December 2020

Total score (TS) data is generated from composite scales consisting of several questions/items, such as the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The analysis method that most fully uses the information gathered is item response theory (IRT) models, but these are complex and require item-level data which may not be available. Therefore, the TS is commonly analysed with standard continuous variable (CV) models, which do not respect the bounded nature of data. Bounded integer (BI) models do respect the data nature but are not as extensively researched. Mixed models for repeated measures (MMRM) are an alternative that requires few assumptions and handles dropout without bias. If an IRT model exists, the expected mean and standard deviation of TS can be computed through IRT-informed functions—which allows CV and BI models to estimate parameters on the IRT scale. The fit, performance on external data and parameter precision (when applicable) of CV, BI and MMRM to analyse simulated TS data from the MDS-UPDRS motor subscale are investigated in this work. All models provided accurate predictions and residuals without trends, but the fit of CV and BI models was improved by IRT-informed functions. The IRT-informed BI model had more precise parameter estimates than the IRT-informed CV model. The IRT-informed models also had the best performance on external data, while the MMRM model was worst. In conclusion, (1) IRT-informed functions improve TS analyses and (2) IRT-informed BI models had more precise IRT parameter estimates than IRT-informed CV models.
Rainbow spacetime from a nonlocal gravitational uncertainty principle
Authors: El-Refy Omar , Masood Syed , Wang Li-Gang , Farag Ali Ahmed
Published: December 2020

The occurrence of spacetime singularities is one of the peculiar features of Einstein gravity, signalling limitation on probing short distances in spacetime. This alludes to the existence of a fundamental length scale in nature. On the contrary, the Heisenberg quantum uncertainty relation seems to allow for probing arbitrarily small length scales. To reconcile these two conflicting ideas in line with a well-known framework of quantum gravity, several modifications of Heisenberg algebra have been proposed. However, it has been extensively argued that such a minimum length would introduce nonlocality in theories of quantum gravity. In this letter, we analyze a previously proposed deformation of the Heisenberg algebra (i.e.,

) for a particle confined in a box subjected to a gravitational field. For the problem in hand, such deformation seems to yield an energy-dependent behavior of spacetime in a way consistent with gravity's rainbow, hence demonstrating a connection between non-locality and gravity's rainbow.
Erratum: Light meson masses from baryon interaction states?
Authors: Trinhammer Ole L.
Published: December 2020

Original article:
EPL, 131 (2020) 31001.
Radiomics for intracerebral hemorrhage: are all small hematomas benign?
Authors: Zhan Chenyi , Chen Qian , Zhang Mingyue , Xiang Yilan , Chen Jie , Zhu Dongqin , Chen Chao , Xia Tianyi , Yang Yunjun
Published: December 2020

Objectives:

We hypothesized that not all small hematomas are benign and that radiomics could predict hematoma expansion (HE) and short-term outcomes in small hematomas.

Methods:

We analyzed 313 patients with small (<10 ml) intracerebral hemorrhage (ICH) who underwent baseline non-contrast CT within 6 h of symptom onset between September 2013 and February 2019. Poor outcome was defined as a Glasgow Outcome Scale score ≤3. A radiomic model and a clinical model were built using least absolute shrinkageand selection operator algorithm or multivariate analysis. A combined model that incorporated the developed radiomic score and clinical factors was then constructed. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of these models.

Results:

The addition of radiomics to clinical factors significantly improved the prediction performance of HE compared with the clinical model alone in both the training {AUC, 0.762 [95% CI (0.665–0.859)] versus AUC, 0.651 [95% CI (0.556–0.745)], p = 0.007} and test {AUC, 0.776 [95% CI (0.655–0.897) versus AUC, 0.631 [95% CI (0.451–0.810)], p = 0.001} cohorts. Moreover, the radiomic-based model achieved good discrimination ability of poor outcomes in the 3–10 ml group (AUCs 0.720 and 0.701).

Conclusion:

Compared with clinical information alone, combined model had greater potential for discriminating between benign and malignant course in patients with small ICH, particularly 3–10 ml hematomas.

Advances in knowledge:

Radiomics can be used as a supplement to conventional medical imaging, improving clinical decision-making and facilitating personalized treatment in small ICH.
Risk Arbitrage Opportunities for Stock Index Options
Authors: Post Thierry , Longarela Iňaki Rodríguez
Published: December 2020

Research about equity index options has shown that option prices systematically violate rational pricing bounds for the risk-averse representative investor. These results raise the question of whether profitable trading possibilities exist in this market. Standard portfolio optimization does not apply because of the large bid-ask spreads and low quote sizes in this market. Motivated by these complications, a system of linear inequalities is developed that completely characterizes all risk arbitrage opportunities in the presence of transaction costs and portfolio restrictions. The practical use of this system is illustrated with an application to front-month S&P500 stock index options. Small-scale portfolios seem to produce surprisingly large abnormal returns out of sample; outperformance, however, seems elusive for institutional investors because of the limited quote size, possibly reflecting data limitations.
Challenges of implementing voluntary assisted dying in Victoria, Australia
Authors: O'Connor Margaret , Philips Janet
Published: December 2020

Background:

Staff working in community palliative care services are accustomed to the intimate conversations that a patient being at home can engender. Being at home can provide a safe space for a patient to express difficulties, including expressing a desire for hastened death. With the implementation of voluntary assisted dying in Victoria in mid-2019, palliative care services have needed to review and adapt policies and practices to incorporate this new procedure. While it was anticipated that a small percentage of people would request access to voluntary assisted dying, in the wake of such significant change, there were numerous implications for palliative care services to consider. This paper describes both the organisational and individual changes undertaken by one community-based palliative care service, in anticipation of legalised assistance in dying. The range of responses to the issues raised are discussed, in preparation for, and in the early days of, voluntary assisted dying.
Bladder and bowel preferences of patients at the end of life: a scoping review
Authors: Smith Nicholas , Rajabali Saima , Hunter Kathleen F , Chambers Thane , Fasinger Robin , Wagg Adrian
Published: December 2020

Background:

Following patient preferences at the end of life should improve outcomes of care, yet patient preferences regarding bladder and bowel care are not often accommodated, as they are not well known in the literature.

Aims:

This scoping review sought to identify bladder and bowel care preferences of patients at the end of life in published literature.

Methods:

Papers published in or after 1997 (in English) that focused on adult preferences for bladder and bowel care at the end of life were included.

Findings:

Scant literature exists on preferences for bladder and bowel care for adult patients at end of life. Further investigation is warranted to arrive at a better understanding of preferences regarding bladder and bowel symptom management.

Conclusions:

Future research should explore if prioritising the symptoms caused by incontinence, among the many symptoms experienced at the end of life, could be achieved through careful questioning and development of a standardised tool focused on improving patient care and incorporating patient preferences for care.
Nursing diagnoses clusters: survival and comfort in oncology end-of-life care
Authors: Marques Karine , Alves Cristine
Published: December 2020

Background:

Holistic care and nursing diagnoses are essential in end-of-life, since interventions based on these ensure greater patient comfort and quality of life.

Aims:

To identify clusters of nursing diagnoses and repercussions for patient comfort and survival.

Methods:

A prospective cohort of 66 end-of-life patients with cancer was examined. Diagnostic groupings were created based on the Kolcaba's theory of comfort. Pearson's chi-square test and Kaplan–Meier estimator were used to assess the relationship between clusters, comfort, and survival.

Findings:

Three diagnostic groups and 23 nurse diagnoses were used. The first and most prevalent diagnosis cluster was related to intestinal tract disorders and sleep. The second was related to neuropsychological characteristics and fatigue associated with lower survival, while the third cluster was related to functionality and perception, which was shown to be associated with less comfort.

Conclusion:

The three clusters were significantly associated with comfort and survival.
Clinical application of photobiomodulation therapy in a zoological setting
Authors: Sparrow Sophie
Published: December 2020

Photobiomodulation therapy (PBMT) uses wavelengths of light that have biostimulatory effects on target tissues. This results in three primary therapeutic effects: anti-inflammatory, analgesia and the regeneration of damaged tissues. The application of PBMT is non-invasive, painless and is often used as an adjunctive therapy to multimodal treatment approaches in zoological settings. Individual treatment plans are required; plans must consider species variability in patient size, skin thickness, coat colour and the depth of the target tissue. Treatment can often be achieved through positive reinforcement training and in a minimally invasive way to ensure the welfare of the patient. The medical benefits of PBMT in zoo animals are poorly described in the literature and confounding factors make it challenging to prove treatment efficacy.
Inter-ground-state crossover resonances formed in atomic vapor by a
dual-frequency laser
Authors: Chang Pengyuan , Pan Duo , Shang Haosen , Shi Tiantian , Luo Bin , Guo Hong , Chen Jingbiao
Published: December 2020

We present a study of the saturated-absorption spectroscopy with crossover resonances involving both Cs hyperfine ground-state levels using a dual-frequency laser tuned to the Cs

line. The crossover resonances are formed by the atomic velocity groups on resonance with both of the dual-frequency laser beams, which are counter-propagated through the vapor cell. A large increase in Doppler-free atomic absorption is observed for certain frequency differences of the dual-frequency laser. This phenomenon is explained by optical pumping and velocity selective optical pumping, imposed by the dual-frequency laser with frequency differences close to but not exactly equal to the level spacing of the two participating ground-state levels. The results obtained in this system are of great interest for laser spectroscopy.
Effects of vector magnetic field on electromagnetically induced transparency with lin ⊥ lin polarization
Authors: Das Bankim Chandra , Das Arpita , Bhattacharyya Dipankar , De Sankar
Published: December 2020

The effect of a vector magnetic field was studied on electromagnetically induced transparency (EIT) with linear

⊥

linear polarization of the probe and pump beams in

87

R
b

−

D
2

transition with a vapor cell at room temperature. The dependence of EIT on the direction of the quantization axis and the relative orientation of the polarizations of the applied electric fields was studied experimentally. We show that from the relative strengths of

σ

and

π

EITs, the direction of the magnetic field can be found. Moreover, from the relative separation between

σ

and

π

EITs, the strength of the magnetic field can be calculated. We also demonstrate that the EIT peak amplitudes show oscillatory behavior depending upon the orientation of the laser polarization relative to the magnetic field direction. To understand the experimental observations, a theoretical study was done numerically considering all 13 Zeeman sub-levels. Apart from the numerical simulation, a toy model was also constructed to obtain an analytical response of the medium considering the velocity distribution. The dependencies of the magnetic field direction and polarization direction of the electric field were explicitly derived with the analytical model.
Applications of the elastic modes of a circular plate in wavefront correction of the adaptive optics and the active optics
Authors: Wang Hairen , Zhang Mingzhu , Gao Jingjing , Lan Yue , Zuo Yingxi , Zheng Xianzhong
Published: December 2020

The elastic modes of a general circular thin plate (EMCTP), reflecting the natural deformation of the resonance, are applied to the diffraction theory of the optical aberrations in this paper. Our work has shown that the mode shapes of the EMCTP resemble those of the Zernike polynomials. As an application example, the compensations of some low order aberrations of the 2.5 m-wide field survey telescope (WFST) have been performed with the EMCTP. Moreover, a quantitative comparative study of the active optics corrections for the EMCTP and the Zernike polynomials is presented in the numerical analysis. The quantitative analysis results have demonstrated that the efficiency of the EMCTP is superior to the standard Zernike polynomials as well as the annular Zernike polynomials.
Automatic, high-speed, high-precision acquisition scheme with QPD for the Taiji program
Authors: Gao Ruihong , Liu Heshan , Zhao Ya , Luo Ziren , Jin Gang
Published: December 2020

Most of the space gravitational wave detection missions, such as the Taiji program, use space-based laser interferometer to sense the gravitational waves. However, to obtain the interference signal, the inter-satellite laser acquisition scheme is firstly required to establish the laser link. Traditional acquisition sensors are CCD cameras, which cause a serious heating problem and call for high alignment precision. To avoid these questions, a high-speed, high-precision, fully automatic acquisition scheme with quadrant photodetectors (QPD) is proposed in this paper. Incoherent measurement method of the QPD is introduced to fulfill high-speed acquisition, while a dedicated imaging system is involved for automatic acquisition. Also, an improved differential power sensing (DPS) signal is developed. Combined with the down-sampling algorithm and the match filter algorithm, the acquisition scheme can achieve 1 µrad resolution with total scanning time less than 220 s.
On the modeling of thermal and free carrier nonlinearities in silicon-on-insulator microring resonators
Authors: Borghi Massimo , Bazzanella Davide , Mancinelli Mattia , Pavesi Lorenzo
Published: December 2020

The temporal dynamics of integrated silicon resonators has been modeled using a set of equations coupling the internal energy, the temperature and the free carrier population. Owing to its simplicity, Newton’s law of cooling is the traditional choice for describing the thermal evolution of such systems. In this work, we theoretically and experimentally prove that this can be inadequate in monolithic planar devices, leading to inaccurate predictions. A new equation that we train to reproduce the correct temperature behaviour is introduced to fix the discrepancies with the experimental results. We discuss the limitations and the range of validity of our refined model, identifying those cases where Netwon’s law provides, nevertheless, accurate solutions. Our modeling describes the phenomena underlying thermal and free carrier instabilities and is a valuable tool for the engineering of photonic systems which rely on resonator dynamical states, such as all optical spiking neural networks or reservoirs for neuromorphic computing.
Quantum-confined Stark effect and mechanisms of its screening in InGaN/GaN light-emitting diodes with a tunnel junction
Authors: Pieniak K. , Chlipala M. , Turski H. , Trzeciakowski W. , Muziol G. , Staszczak G. , Kafar A. , Makarowa I. , Grzanka E. , Grzanka S. , Skierbiszewski C. , Suski T.
Published: December 2020

Nitride-based light-emitting diodes (LEDs) are well known to suffer from a high built-in electric field in the quantum wells (QWs). In this paper we determined to what extent the electric field is screened by injected current. In our approach we used high pressure to study this evolution. In LEDs with a narrow QW (2.6 nm) we found that even at a high injection current a large portion of built-in field remains. In LEDs with very wide QWs (15 and 25 nm) the electric field is fully screened even at the lowest currents. Furthermore, we examined LEDs with a tunnel junction in two locations – above and below the active region. This allowed us to study the cases of parallel and antiparallel fields in the well and in the barriers.
All-optical gain optoelectronic oscillator based on a dual-frequency integrated semiconductor laser: potential to break the bandwidth limitation in the traditional OEO configuration
Authors: Li Jin , Pu Tao , Zheng Jilin , Zhang Yunshan , Shi Yuechun , Shao Wei , Zhang Xin , Meng Xianshuai , Liu Jie , Liu Juan , Chen Xiangfei
Published: December 2020

A novel photonic method, to the best of our knowledge, to generate high-frequency micro/millimeter-wave signals based on the optoelectronic oscillator (OEO) with all-optical gain is proposed in this paper. The core device is the monolithically integrated dual-frequency semiconductor laser (MI-DFSL), in which the two DFB laser sections are simultaneously fabricated on one chip. Attributing to the combined impact of the photon-photon resonance effect and the sideband amplification injection locking effect, one widely tunable microwave photonic filter with a high Q value and narrow 3-dB bandwidth can be realized. In this case, the generated microwave signals would largely break the limitation in bandwidth once making full use of the optical amplifier to replace the narrow-band electrical amplifiers in traditional OEO configuration to provide the necessary gain. No additional high-speed external modulator, high-frequency electrical bandpass filters or multi-stage electrical amplifiers are required, highly simplifying the framework and reducing the power consumption. Moreover, this simple and compact structure has the potential to be developed for photonic integration. In the current proof-of-concept experiment, microwave signals with wide tuning ranges from 14.2 GHz to 25.2 GHz are realized. The SSB phase noises in all tuning range are below -103.77 dBc/Hz at 10 kHz and the best signal of the -106.363 dBc/Hz at 10 kHz is achieved at the frequency of 17.2 GHz.
Using an injection-locked VCSEL to produce Fourier-transform-limited optical pulses
Authors: Rowland Jed , Perrella Christopher , Light Philip , Sparkes Ben M. , Luiten Andre N.
Published: December 2020

In this Letter, we present Fourier-transform-limited, nanosecond scale optical pulses from a vertical cavity surface emitting laser (VCSEL) using injection locking with a narrow-band seed laser. We examine two different injection-locking architectures and show that we can achieve an effective injection-locking range of over 8 GHz with an extinction ratio of 20,000:1. These results indicate that injection-locked VCSELs could become a key component of large-scale photonic quantum networks.
Pre-test probability for SARS-Cov-2-related infection score: The PARIS score
Authors: Tordjman Mickael , Mekki Ahmed , Mali Rahul D. , Saab Ines , Chassagnon Guillaume , Guillo Enora , Burns Robert , Eshagh Deborah , Beaune Sebastien , Madelin Guillaume , Bessis Simon , Feydy Antoine , Mihoubi Fadila , Doumenc Benoit , Mouthon Luc , Carlier Robert-Yves , Drapé Jean-Luc , Revel Marie-Pierre
Published: December 2020

Introduction

In numerous countries, large population testing is impossible due to the limited availability of RT-PCR kits and CT-scans. This study aimed to determine a pre-test probability score for SARS-CoV-2 infection.

Methods

This multicenter retrospective study (4 University Hospitals) included patients with clinical suspicion of SARS-CoV-2 infection. Demographic characteristics, clinical symptoms, and results of blood tests (complete white blood cell count, serum electrolytes and CRP) were collected. A pre-test probability score was derived from univariate analyses of clinical and biological variables between patients and controls, followed by multivariate binary logistic analysis to determine the independent variables associated with SARS-CoV-2 infection.

Results

605 patients were included between March 10th and April 30th, 2020 (200 patients for the training cohort, 405 consecutive patients for the validation cohort). In the multivariate analysis, lymphocyte (<1.3 G/L), eosinophil (<0.06 G/L), basophil (<0.04 G/L) and neutrophil counts (<5 G/L) were associated with high probability of SARS-CoV-2 infection but no clinical variable was statistically significant. The score had a good performance in the validation cohort (AUC = 0.918 (CI: [0.891–0.946]; STD = 0.014) with a Positive Predictive Value of high-probability score of 93% (95%CI: [0.89–0.96]). Furthermore, a low-probability score excluded SARS-CoV-2 infection with a Negative Predictive Value of 98% (95%CI: [0.93–0.99]). The performance of the score was stable even during the last period of the study (15-30th April) with more controls than infected patients.

Conclusions

The PARIS score has a good performance to categorize the pre-test probability of SARS-CoV-2 infection based on complete white blood cell count. It could help clinicians adapt testing and for rapid triage of patients before test results.
The importance of urban natural areas and urban ecosystem services during the COVID-19 pandemic
Authors: Grima Nelson , Corcoran Will , Hill-James Corinne , Langton Benjamin , Sommer Haley , Fisher Brendan
Published: December 2020

Urban, peri-urban forests and other natural areas provide a wide range of material and non-material benefits to people known as ecosystem services. Access to these areas has been linked to benefits for physical and mental health of local populations. In the spring of 2020, the COVID-19 global pandemic forced many governments to impose a set of restrictions including the closure of businesses, cancelation of public events and schooling, social distancing, limitations on the size of social gatherings, and travel restrictions. During this period of restrictions, we conducted a study assessing the importance of urban and peri-urban forests and other natural areas to people living in and around the city of Burlington, Vermont, USA. We evaluated the self-reported use and changes in personal importance related to these natural areas before and during the period of restrictions. We received over 400 responses to our field survey. The results show that 69.0% of the respondents had increased or greatly increased their visitation rate to our natural areas and urban forests, and 80.6% of respondents considered that the importance of these areas, and access to them, either increased or greatly increased. Moreover 25.8% of the sample had either never, or very rarely accessed their local natural areas before the pandemic, but 69.2% of the first time or infrequent visitors reported that having access to these areas during COVID-19 as ‘very important’. People reported that these areas were important for a wide range of activities from exercise to birding, but also reported values related to reducing stress in a time of global chaos. Our results indicate the increasing demand and value of such areas in times of crisis such as COVID-19. Experts in zoonotic disease predict the potential for more frequent pandemic events, thus predicating the importance for continued funding for, maintenance of, and improved access to, natural areas to our largely urban civilization.
Coronavirus-induced coagulopathy during the course of disease
Authors: Friedrich Marie Sophie , Studt Jan-Dirk , Braun Julia , Spahn Donat R. , Kaserer Alexander
Published: December 2020

Background

A significant proportion of patients with coronavirus disease 19 (COVID-19) suffer from excessive coagulation activation and coagulopathy which is associated with an increased risk of venous and arterial thromboembolism and adverse outcome. Our study investigates coagulation markers and the incidence of thromboembolic events in COVID-19 patients receiving recommended anticoagulation strategies.

Methods

In a retrospective single-center analysis at the University Hospital Zurich, Switzerland, we investigated 31 adult COVID-19 patients between April 6thand May 13th, 2020 and with at least one laboratory assessment of the coagulation markers prothrombin time/Quick, thrombin time, fibrinogen and D-dimers. For antithrombotic prophylaxis low-molecular-weight-heparin or unfractionated heparin was administered and two patients with heparin-induced thrombocytopenia received argatroban.

Results

We analyzed 31 patients (68% male, mean age 60± SD 15 years). 22 (71%) of these required intensive care unit treatment, 5 (16%) were hospitalized in a ward, and 4 (13%) were outpatients. Mean fibrinogen levels were markedly elevated to 6.4± SD 1.8g/l, with a peak in the third week of the disease and no significant decrease over time. D-dimers were elevated to a mean value of 5.1±4.4mg/l with peak levels of 6.8±5.3mg/l in the fourth week of disease, and a subsequent decrease. Platelet count (308±136G/l) and PT/Quick (85±22%) showed no significant changes over time. Sensitivity analyses for patients treated in the ICU showed that D-dimer levels were higher in this group. The results of other sensitivity analyses were comparable. Thromboembolic events were diagnosed in 4 (13%) patients and 5 (16%) patients died during the observation period.

Conclusion

We find coagulation alterations in COVID-19 patients indicating significant hypercoagulability. These alterations are visible despite antithrombotic treatment, and peak around week 3–4 of the disease.
Effect of family history, occupation and diet on the risk of Parkinson disease: A case-control study
Authors: Torti Margherita , Fossati Chiara , Casali Miriam , De Pandis Maria Francesca , Grassini Paola , Radicati Fabiana Giada , Stirpe Paola , Vacca Laura , Iavicoli Ivo , Leso Veruscka , Ceppi Marcello , Bruzzone Marco , Bonassi Stefano , Stocchi Fabrizio
Published: December 2020

Background

The aetiology of Parkinson’s disease (PD) is still very controversial, with a peculiar lack of established risk factors or protective behavior.

Methods

We carried out a case–control study of 634 idiopathic PD patients admitted from 2011 to 2015 to two hospitals located in central Italy and 532 controls matched by hospital, gender and age (± 5 years). The study questionnaire included questions on host factors, family history, residence, occupation and lifestyle. Odds ratios (ORs) for PD and 95% confidence intervals (CIs) were estimated with logistic regression, adjusting for actual and potential confounders.

Results

A lower OR was observed in females (0.74; 95%CI:0.58–0.96), while older age classes showed a constantly increased risk for PD (p<0.005) starting from the class 65–69 years. Subjects who reported a first degree relative affected by PD showed a borderline increase which was more evident in those enrolled in the urban center of Rome (OR = 1.65; 95%CI: 1.09–2.50). Significant reduction of the risk was associated to current smoking (OR = 0.48; 95%CI: 0.24–0.54), and to vegetables consumption (p<0.03), while borderline increases were associated to meat and cold cut consumption. Occupational activities classified according to ISCO-08 categories did not show increased risk, while higher ORs’ were found for pilots and physicians.

Conclusions

The results from this study confirmed the higher risk of PD in males and in elderly, and the inverse association with smoking habit. The possible etiological role of familial clustering, dietary habit, and some job tasks is suggested.
An ecological study to evaluate the association of Bacillus Calmette-Guerin (BCG) vaccination on cases of SARS-CoV2 infection and mortality from COVID-19
Authors: Chimoyi Lucy , Velen Kavindhran , Churchyard Gavin J. , Wallis Robert , Lewis James J. , Charalambous Salome
Published: December 2020

As the SARS-CoV2 pandemic has progressed, there have been marked geographical differences in the pace and extent of its spread. We evaluated the association of BCG vaccination on morbidity and mortality of SARS-CoV2, adjusted for country-specific responses to the epidemic, demographics and health. SARS-CoV2 cases and deaths as reported by 31 May 2020 in the World Health Organization situation reports were used. Countries with at least 28 days following the first 100 cases, and available information on BCG were included. We used log-linear regression models to explore associations of cases and deaths with the BCG vaccination policy in each country, adjusted for population size, gross domestic product, proportion aged over 65 years, stringency level measures, testing levels, smoking proportion, and the time difference from date of reporting the 100th case to 31 May 2020. We further looked at the association that might have been found if the analyses were done at earlier time points. The study included 97 countries with 73 having a policy of current BCG vaccination, 13 having previously had BCG vaccination, and 11 having never had BCG vaccination. In a log-linear regression model there was no effect of country-level BCG status on SARS-CoV2 cases or deaths. Univariable log-linear regression models showed a trend towards a weakening of the association over time. We found no statistical evidence for an association between BCG vaccination policy and either SARS-CoV2 morbidity or mortality. We urge countries to rather consider alternative tools with evidence supporting their effectiveness for controlling SARS-CoV2 morbidity and mortality.
Development and validation of a NanoString BASE47 bladder cancer gene classifier
Authors: Kardos Jordan , Rose Tracy L. , Manocha Ujjawal , Wobker Sara E. , Damrauer Jeffrey S. , Bivalaqua Trinity J. , Kates Max , Moore Kristin J. , Parker Joel S. , Kim William Y.
Published: December 2020

Background

Recent molecular characterization of urothelial cancer (UC) has suggested potential pathways in which to direct treatment, leading to a host of targeted therapies in development for UC. In parallel, gene expression profiling has demonstrated that high-grade UC is a heterogeneous disease. Prognostic basal-like and luminal-like subtypes have been identified and an accurate transcriptome BASE47 classifier has been developed. However, these phenotypes cannot be broadly investigated due to the lack of a clinically viable diagnostic assay. We sought to develop and evaluate a diagnostic classifier of UC subtype with the goal of accurate classification from clinically available specimens.

Methods

Tumor samples from 52 patients with high-grade UC were profiled for BASE47 genes concurrently by RNAseq as well as NanoString. After design and technical validation of a BASE47 NanoString probeset, results from the RNAseq and NanoString were used to translate diagnostic criteria to the Nanostring platform. Evaluation of repeatability and accuracy was performed to derive a final Nanostring based classifier. Diagnostic classification resulting from the NanoString BASE47 classifier was validated on an independent dataset (n = 30). The training and validation datasets accurately classified 87% and 93% of samples, respectively.

Results

Here we have derived a NanoString-platform BASE47 classifier that accurately predicts basal-like and luminal-like subtypes in high grade urothelial cancer. We have further validated our new NanoString BASE47 classifier on an independent dataset and confirmed high accuracy when compared with our original Transcriptome BASE47 classifier.

Conclusions

The NanoString BASE47 classifier provides a faster turnaround time, a lower cost per sample to process, and maintains the accuracy of the original subtype classifier for better clinical implementation.
A strategic expression method of miR-29b and its anti-fibrotic effect based on RNA-sequencing analysis
Authors: Fan Xiaoming , Gao Yingnyu , Zhang Xiaolu , Lughmani Haroon Y. , Kennedy David J. , Haller Steven T. , Pierre Sandrine V. , Shapiro Joseph I. , Tian Jiang
Published: December 2020

Tissue fibrosis is a significant health issue associated with organ dysfunction and failure. Increased deposition of collagen and other extracellular matrix (ECM) proteins in the interstitial area is a major process in tissue fibrosis. The microRNA-29 (miR-29) family has been demonstrated as anti-fibrotic microRNAs. Our recent work showed that dysregulation of miR-29 contributes to the formation of cardiac fibrosis in animal models of uremic cardiomyopathy, whereas replenishing miR-29 attenuated cardiac fibrosis in these animals. However, excessive overexpression of miR-29 is a concern because microRNAs usually have multiple targets, which could result in unknown and unexpected side effect. In the current study, we constructed a novel Col1a1-miR-29b vector using collagen 1a1 (Col1a1) promoter, which can strategically express miR-29b-3p (miR-29b) in response to increased collagen synthesis and reach a dynamic balance between collagen and miR-29b. Our experimental results showed that in mouse embryonic fibroblasts (MEF cells) transfected with Col1a1-miR-29b vector, the miR-29b expression is about 1000 times less than that in cells transfected with CMV-miR-29b vector, which uses cytomegalovirus (CMV) as a promoter for miR-29b expression. Moreover, TGF-β treatment increased the miR-29b expression by about 20 times in cells transfected with Col1a1-miR-29b, suggesting a dynamic response to fibrotic stimulation. Western blot using cell lysates and culture media demonstrated that transfection of Col1a1-miR-29b vector significantly reduced TGF-β induced collagen synthesis and secretion, and the effect was as effective as the CMV-miR-29b vector. Using RNA-sequencing analysis, we found that 249 genes were significantly altered (180 upregulated and 69 downregulated, at least 2-fold change and adjusted p-value <0.05) after TGF-β treatment in MEF cells transfected with empty vector. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using GAGE R-package showed that the top 5 upregulated pathways after TGF-β treatment were mostly fibrosis-related, including focal adhesion, ECM reaction, and TGF-β signaling pathways. As expected, transfection of Col1a1-miR-29b or CMV-miR-29b vector partially reversed the activation of these pathways. We also analyzed the expression pattern of the top 100 miR-29b targeting genes in these cells using the RNA-sequencing data. We identified that miR-29b targeted a broad spectrum of ECM genes, but the inhibition effect is mostly moderate. In summary, our work demonstrated that the Col1a1-miR-29b vector can be used as a dynamic regulator of collagen and other ECM protein expression in response to fibrotic stimulation, which could potentially reduce unnecessary side effect due to excessive miR-29b levels while remaining an effective potential therapeutic approach for fibrosis.
Dopamine production in the brain is associated with caste-specific morphology and behavior in an artificial intermediate honey bee caste
Authors: Sasaki Ken , Harada Mariko
Published: December 2020

Caste polymorphism in eusocial insects is based on morphological plasticity and linked to physiological and behavioral characteristics. To test the possibility that dopamine production in the brain is associated with the caste-specific morphology and behavior in female honey bees, an intermediate caste was produced via artificial rearing using different amounts of diet, before quantifying the dopamine levels and conducting behavioral tests. In field colonies, individual traits such as mandibular shape, number of ovarioles, diameter of spermatheca, and dopamine levels in the brain differed significantly between workers and queens. Females given 1.5 times the amount of artificial diet that control worker receives during the larval stage in the laboratory had characteristics intermediate between castes. The dopamine levels in the brain were positively correlated with the mandibular shape indexes, number of ovarioles, and spermatheca diameter among artificially reared females. The dopamine levels were significantly higher in females with mandibular notches than those without. In fighting experiments with the intermediate caste females, the winners had significantly higher dopamine levels in the brain than the losers. Brain levels of tyrosine were positively correlated with those of catecholamines but not phenolamines, thereby suggesting a strong metabolic relationship between tyrosine and dopamine. Thus, the caste-specific characteristics of the honey bee are potentially continuous in the same manner as those in primitively eusocial species. Dopamine production in the brain is associated with the continuous caste-specific morphology, as well as being linked to the amount of tyrosine taken from food, and it supports the aggressive behavior of queen-type females.
Repeatability of baited remote underwater video station (BRUVS) results within and between seasons
Authors: Sherman C. Samantha , Heupel Michelle R. , Johnson Mohini , Kaimuddin Muslimin , Qamar L. M. Sjamsul , Chin Andrew , Simpfendorfer Colin A.
Published: December 2020

Baited remote underwater video stations (BRUVS) are increasingly being used to evaluate and monitor reef communities. Many BRUVS studies compare multiple sites sampled at single time points that may differ from the sampling time of another site. As BRUVS use grows in its application to provide data relevant to sustainable management, marine protected area success, and overall reef health, understanding repeatability of sampling results is vital. We examined the repeatability of BRUVS results for the elasmobranch community both within and between seasons and years, and explored environmental factors affecting abundances at two sites in Indonesia. On 956 BRUVS, 1139 elasmobranchs (69% rays, 31% sharks) were observed. We found consistent results in species composition and abundances within a season and across years. However, elasmobranch abundances were significantly higher in the wet season. The elasmobranch community was significantly different between the two sites sampled, one site being more coastal and easily accessed by fishermen. Our results demonstrate that while BRUVS are a reliable and repeatable method for surveying elasmobranchs, care must be taken in the timing of sampling between different regions to ensure that any differences observed are due to inherent differences amongst sampling areas as opposed to seasonal dissimilarities.
A multistationary loop model of ALS unveils critical molecular interactions involving mitochondria and glucose metabolism
Authors: Burlando Bruno , Milanese Marco , Giordano Giulia , Bonifacino Tiziana , Ravera Silvia , Blanchini Franco , Bonanno Giambattista
Published: December 2020

Amyotrophic lateral sclerosis (ALS) is a poor-prognosis disease with puzzling pathogenesis and inconclusive treatments. We develop a mathematical model of ALS based on a system of interactive feedback loops, focusing on the mutant SOD1G93A mouse. Misfolded mutant SOD1 aggregates in motor neuron (MN) mitochondria and triggers a first loop characterized by oxidative phosphorylation impairment, AMP kinase over-activation, 6-phosphofructo-2-kinase (PFK3) rise, glucose metabolism shift from pentose phosphate pathway (PPP) to glycolysis, cell redox unbalance, and further worsening of mitochondrial dysfunction. Oxidative stress then triggers a second loop, involving the excitotoxic glutamatergic cascade, with cytosolic Ca2+ overload, increase of PFK3 expression, and further metabolic shift from PPP to glycolysis. Finally, cytosolic Ca2+ rise is also detrimental to mitochondria and oxidative phosphorylation, thus closing a third loop. These three loops are overlapped and positive (including an even number of inhibitory steps), hence they form a candidate multistationary (bistable) system. To describe the system dynamics, we model the interactions among the functional agents with differential equations. The system turns out to admit two stable equilibria: the healthy state, with high oxidative phosphorylation and preferential PPP, and the pathological state, with AMP kinase activation, PFK3 over expression, oxidative stress, excitotoxicity and MN degeneration. We demonstrate that the loop system is monotone: all functional agents consistently act toward the healthy or pathological condition, depending on low or high mutant SOD1 input. We also highlight that molecular interactions involving PFK3 are crucial, as their deletion disrupts the system’s bistability leading to a single healthy equilibrium point. Hence, our mathematical model unveils that promising ALS management strategies should be targeted to mechanisms that keep low PFK3 expression and activity within MNs.
Genetic deletion of connexin 37 causes polyuria and polydipsia
Authors: Xue Jianxiang , Thomas Linto , Dominguez Rieg Jessica A. , Fenton Robert A. , Rieg Timo
Published: December 2020

The connexin 37 (Cx37) channel is clustered at gap junctions between cells in the renal vasculature or the renal tubule where it is abundant in basolateral cell interdigitations and infoldings of epithelial cells in the proximal tubule, thick ascending limb, distal convoluted tubule and collecting duct; however, physiological data regarding its role are limited. In this study, we investigated the role of Cx37 in fluid homeostasis using mice with a global deletion of Cx37 (Cx37-/-mice). Under baseline conditions, Cx37-/-had ~40% higher fluid intake associated with ~40% lower urine osmolality compared to wild-type (WT) mice. No differences were observed between genotypes in urinary adenosine triphosphate or prostaglandin E2, paracrine factors that alter renal water handling. After 18-hours of water deprivation, plasma aldosterone and urine osmolality increased significantly in Cx37-/-and WT mice; however, the latter remained ~375 mmol/kg lower in Cx37-/-mice, an effect associated with a more pronounced body weight loss despite higher urinary AVP/creatinine ratios compared to WT mice. Consistent with this, fluid intake in the first 3 hours after water deprivation was 37% greater in Cx37-/-vs WT mice. Cx37-/-mice showed significantly lower renal AQP2 abundance and AQP2 phosphorylation at serine 256 than WT mice in response to vehicle or dDAVP, suggesting a partial contribution of the kidney to the lower urine osmolality. The abundance and responses of the vasopressin V2receptor, AQP3, NHE3, NKCC2, NCC, H+-ATPase, αENaC, γENaC or Na+/K+-ATPase were not significantly different between genotypes. In summary, these results demonstrate that Cx37 is important for body water handling.
taman raudhatul sakinah
Authors: AKHTAR SALMA
Published: December 2020

RAUDHATUL SAKINAH Normally the burial ground is a startling spot and is just visited by the individuals who need to visit the expired relatives and discuss Quran refrains and petitions for them . For this situation, the sentiment of guests is occupied to the individuals who have gone and may have been sickened peacefully in such a domain .