bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetically predicted serum vitamin D and COVID-19: a Mendelian randomisation study
Authors: Patchen Bonnie K , Clark Andrew G , Gaddis Nathan , Hancock Dana B , Cassano Patricia A
Published: May 2021

Objectives

To investigate causality of the association of serum vitamin D with the risk and severity of COVID-19 infection.

Design

Two-sample Mendelian randomisation study.

Setting

Summary data from genome-wide analyses in the population-based UK Biobank and SUNLIGHT Consortium, applied to meta-analysed results of genome-wide analyses in the COVID-19 Host Genetics Initiative.

Participants

17 965 COVID-19 cases including 11 085 laboratory or physician-confirmed cases, 7885 hospitalised cases and 4336 severe respiratory cases, and 1 370 547 controls, primarily of European ancestry.

Exposures

Genetically predicted variation in serum vitamin D status, instrumented by genome-wide significant single nucleotide polymorphisms (SNPs) associated with serum vitamin D or risk of vitamin D deficiency/insufficiency.

Main outcome measures

Susceptibility to and severity of COVID-19 infection, including severe respiratory infection and hospitalisation.

Results

Mendelian randomisation analysis, sufficiently powered to detect effects comparable to those seen in observational studies, provided little to no evidence for an effect of genetically predicted serum vitamin D on susceptibility to or severity of COVID-19 infection. Using SNPs in loci related to vitamin D metabolism as genetic instruments for serum vitamin D concentrations, the OR per SD higher serum vitamin D was 1.04 (95% CI 0.92 to 1.18) for any COVID-19 infection versus population controls, 1.05 (0.84 to 1.31) for hospitalised COVID-19 versus population controls, 0.96 (0.64 to 1.43) for severe respiratory COVID-19 versus population controls, 1.15 (0.99 to 1.35) for COVID-19 positive versus COVID-19 negative and 1.44 (0.75 to 2.78) for hospitalised COVID-19 versus non-hospitalised COVID-19. Results were similar in analyses using SNPs with genome-wide significant associations with serum vitamin D (ie, including SNPs in loci with no known relationship to vitamin D metabolism) and in analyses using SNPs with genome-wide significant associations with risk of vitamin D deficiency or insufficiency.

Conclusions

These findings suggest that genetically predicted differences in long-term vitamin D nutritional status do not causally affect susceptibility to and severity of COVID-19 infection, and that associations observed in previous studies may have been driven by confounding. These results do not exclude the possibility of low-magnitude causal effects or causal effects of acute responses to therapeutic doses of vitamin D.
Sham treatment effects in manual therapy trials on back pain patients: a systematic review and pairwise meta-analysis
Authors: Lavazza Carolina , Galli Margherita , Abenavoli Alessandra , Maggiani Alberto
Published: May 2021

Objective

To assess the effects and reliability of sham procedures in manual therapy (MT) trials in the treatment of back pain (BP) in order to provide methodological guidance for clinical trial development.

Design

Systematic review and meta-analysis.

Methods and analysis

Different databases were screened up to 20 August 2020. Randomised controlled trials involving adults affected by BP (cervical and lumbar), acute or chronic, were included.

Hand contact sham treatment (ST) was compared with different MT (physiotherapy, chiropractic, osteopathy, massage, kinesiology and reflexology) and to no treatment. Primary outcomes were BP improvement, success of blinding and adverse effect (AE). Secondary outcomes were number of drop-outs. Dichotomous outcomes were analysed using risk ratio (RR), continuous using mean difference (MD), 95% CIs. The minimal clinically important difference was 30 mm changes in pain score.

Results

24 trials were included involving 2019 participants. Very low evidence quality suggests clinically insignificant pain improvement in favour of MT compared with ST (MD 3.86, 95% CI 3.29 to 4.43) and no differences between ST and no treatment (MD -5.84, 95% CI −20.46 to 8.78).

ST reliability shows a high percentage of correct detection by participants (ranged from 46.7% to 83.5%), spinal manipulation being the most recognised technique.

Low quality of evidence suggests that AE and drop-out rates were similar between ST and MT (RR AE=0.84, 95% CI 0.55 to 1.28, RR drop-outs=0.98, 95% CI 0.77 to 1.25). A similar drop-out rate was reported for no treatment (RR=0.82, 95% 0.43 to 1.55).

Conclusions

MT does not seem to have clinically relevant effect compared with ST. Similar effects were found with no treatment. The heterogeneousness of sham MT studies and the very low quality of evidence render uncertain these review findings.

Future trials should develop reliable kinds of ST, similar to active treatment, to ensure participant blinding and to guarantee a proper sample size for the reliable detection of clinically meaningful treatment effects.

PROSPERO registration number

CRD42020198301.
European List of Essential Medicines for Medical Education: a protocol for a modified Delphi study
Authors: Donker Erik , Brinkman David , Richir Milan , Papaioannidou Paraskevi , Likic Robert , Sanz Emilio J , Christiaens Thierry , Costa João , De Ponti Fabrizio , Gatti Milo , Böttiger Ylva , Kramers Cornelis , Garner Sarah , Pandit Rahul , van Agtmael Michiel , Tichelaar Jelle
Published: May 2021

Introduction

Junior doctors are responsible for a substantial number of prescribing errors, and final-year medical students lack sufficient prescribing knowledge and skills just before they graduate. Various national and international projects have been initiated to reform the teaching of clinical pharmacology and therapeutics (CP&T) during undergraduate medical training. However, there is as yet no list of commonly prescribed and available medicines that European doctors should be able to independently prescribe safely and effectively without direct supervision. Such a list could form the basis for a European Prescribing Exam and would harmonise European CP&T education. Therefore, the aim of this study is to reach consensus on a list of widely prescribed medicines, available in most European countries, that European junior doctors should be able to independently prescribe safely and effectively without direct supervision: the European List of Essential Medicines for Medical Education.

Methods and analysis

This modified Delphi study will recruit European CP&T teachers (expert group). Two Delphi rounds will be carried out to enable a list to be drawn up of medicines that are available in ≥80% of European countries, which are considered standard prescribing practice, and which junior doctors should be able to prescribe safely and effectively without supervision.

Ethics and dissemination

The study has been approved by the Medical Ethics Review Committee of VU University Medical Center (no. 2020.335) and by the Ethical Review Board of the Netherlands Association for Medical Education (approved project no. NVMO‐ERB 2020.4.8). The European List of Essential Medicines for Medical Education will be presented at national and international conferences and will be submitted to international peer-reviewed journals. It will also be used to develop and implement the European Prescribing Exam.
Characteristics, outcomes and risk factors for mortality of 522 167 patients hospitalised with COVID-19 in Brazil: a retrospective cohort study
Authors: Castro Marcia C , Gurzenda Susie , Macário Eduardo Marques , França Giovanny Vinícius A
Published: May 2021

Objective

To provide a comprehensive description of demographic, clinical and radiographic characteristics; treatment and case outcomes; and risk factors associated with in-hospital death of patients hospitalised with COVID-19 in Brazil.

Design

Retrospective cohort study of hospitalised patients diagnosed with COVID-19.

Setting

Data from all hospitals across Brazil.

Participants

522 167 hospitalised patients in Brazil by 14 December 2020 with severe acute respiratory illness, and a confirmed diagnosis for COVID-19.

Primary and secondary outcome measures

Prevalence of symptoms and comorbidities was compared by clinical outcomes and intensive care unit (ICU) admission status. Survival was assessed using Kaplan Meier survival estimates. Risk factors associated with in-hospital death were evaluated with multivariable Cox proportional hazards regression.

Results

Of the 522 167 patients included in this study, 56.7% were discharged, 0.002% died of other causes, 30.7% died of causes associated with COVID-19 and 10.2% remained hospitalised. The median age of patients was 61 years (IQR, 47–73), and of non-survivors 71 years (IQR, 60–80); 292 570 patients (56.0%) were men. At least one comorbidity was present in 64.5% of patients and in 76.8% of non-survivors. From illness onset, the median times to hospital and ICU admission were 6 days (IQR, 3–9) and 7 days (IQR, 3–10), respectively; 15 days (IQR, 9–24) to death and 15 days (IQR, 11–20) to hospital discharge. Risk factors for in-hospital death included old age, Black/Brown ethnoracial self-classification, ICU admission, being male, living in the North and Northeast regions and various comorbidities. Age had the highest HRs of 5.51 (95% CI: 4.91 to 6.18) for patients≥80, compared with those ≤20.

Conclusions

Characteristics of patients and risk factors for in-hospital mortality highlight inequities of COVID-19 outcomes in Brazil. As the pandemic continues to unfold, targeted policies that address those inequities are needed to mitigate the unequal burden of COVID-19.
Implementation of theActivateinjury prevention exercise programme in English schoolboy rugby union
Authors: Barden Craig , Stokes Keith A , McKay Carly D
Published: May 2021

Objectives

The implementation of theActivateinjury prevention exercise programme has not been assessed in an applied context. This study aimed to (1) describe the knowledge and perceptions of school rugby coaches and players towards injury risk, prevention andActivateand (2) evaluateActivateimplementation in schoolboy rugby using the reach, effectiveness, adoption, implementation and maintenance framework.

Methods

Bespoke electronic surveys were administered to coaches (including support staff) and players at participating English schools (2018–2020). Most questions and statements were answered using a 7-point Likert scale. At baseline, participants detailed theirActivateawareness and perceptions of injury risk and prevention in schoolboy rugby. At postseason, participants reportedActivateuse throughout the study and their perceptions towards the programme.

Results

At baseline, significant differences existed between coaches (n=106) and players (n=571) inActivateawareness (75% and 13% respectively; χ2=173.5, p<0.001). Coaches perceived rugby had a significantly greater injury risk than players, while holding more positive perceptions towards injury prevention. At postseason, coaches reported greaterActivateadoption compared with players (76% and 18% respectively; χ2=41.8, p<0.001); 45% of players were unaware if they used the programme. Median session adherence was twice weekly, with a median duration of 10–15 min. This suggestsActivatewas not implemented as intended, with recommendations of three 20 min sessions per week. Both groups identified common barriers to implementation, such as lack of time and inclusion of a ball.

Conclusion

Coaches are instrumental in the decision to implementActivate. Targeting behavioural change in these individuals is likely to have the greatest impact on intervention uptake.
Survey on antibiotic regimens for necrotizing enterocolitis prescribed by Chinese pediatricians in 2020
Authors: Zhang Zhongyao , He Yu , Wang Zhengli , Bao Lei , Shi Yuan , Li Luquan
Published: May 2021

Background

Necrotizing enterocolitis (NEC) is a serious intestinal inflammatory disease in neonates, and intravenous antibiotics constitute the main therapeutic strategy. Studies have shown that substantial variation in the selection of antibiotic regimens for NEC remains in many countries. The variability in antibiotic therapy selection in China is unclear.

Methods

A cross-sectional study using an online questionnaire regarding antibiotic regimens for NEC was conducted among pediatricians working in tertiary hospitals in China.

Results

A total of 284 pediatricians from 29 provinces completed the survey; 37.9% of them administered one antibiotic, 56.7% administered two antibiotics and 2.4% administered three antibiotics. The top three single-antibiotic regimens for NEC were beta-lactamase inhibitors (n=66, 41.5%), carbapenems (n=46, 28.9%) and cephalosporins (n=33, 20.8%). Twenty combinations of two antibiotics were identified, and the top three combinations were beta-lactamase inhibitors and antianaerobic agents (n=49, 19.6%), carbapenems and glycopeptides (n=42, 16.8%), and cephalosporins and antianaerobic agents (n=37, 14.8%). Regarding the therapeutic duration of antibiotic treatment, 77.5% (n=220) of the pediatricians chose 5–10 days for stage II NEC, and 79.6% (n=226) chose 7–14 days for stage III NEC. Forty-three percent (n=122) of the respondents preferred to use carbapenems when NEC was diagnosed, and 83.3% (n=135) adjusted the antibiotics to carbapenems if a patient’s medical condition deteriorated or if the therapeutic efficacy was poor.

Conclusion

This survey revealed that carbapenems were the most common antibiotics selected when NEC was diagnosed or a patient’s condition deteriorated, but the duration of the course of treatment for NEC varied substantially among doctors.
A novel approach for nearly-coincident events rejection
Authors: Borghesi M. , De Gerone M. , Faverzani M. , Fedkevych M. , Ferri E. , Gallucci G. , Giachero A. , Nucciotti A. , Puiu A.
Published: May 2021

We present a novel technique, called DSVP (Discrimination through Singular Vectors Projections), to discriminate spurious events within a dataset. The purpose of this paper is to lay down a general procedure which can be tailored for a broad variety of applications. After describing the general concept, we apply the algorithm to the problem of identifying nearly coincident events in low temperature microcalorimeters in order to push the time resolution close to its intrinsic limit. In fact, from simulated datasets it was possible to achieve an effective time resolution even shorter than the sampling time of the system considered. The obtained results are contextualized in the framework of the HOLMES experiment, which aims at directly measuring the neutrino mass with the calorimetric approach, allowing to significally improve its statistical sensitivity.
The Relationships among Hydrogen Adsorption, CO Stripping, and Selectivity of CO2 Reduction on Pd Nanoparticles
Authors: Guo Ren-Hao , Hu Chi-Chang
Published: May 2021

The low formation overpotential and strong adsorption ability of CO on palladium surface sites constrain the lower potential limit and current density of the electrochemical reduction of CO2 (CO2ER) to formate on Pd although this reaction has been considered one of the most effective methods for CO2 recycling. Among various factors, the participation of adsorbed hydrogen atoms seems to be a key factor affecting the selectivity of CO2ER on Pd. This article discusses the relationship between the selectivity and hydrogen adsorption on the Pd nanoparticles/carbon (Pd/XC72) catalyst through two kinds of systems: gas diffusion electrode (GDE) and rotating ring disk electrode (RRDE). The main product of the CO2ER on Pd/XC72 is changed from formate to CO when both the terrace and step sites of Pd particles are under a low coverage of adsorbed H atoms. In addition, the progress of CO self-poisoning on the Pd/XC72 catalyst and the peak corresponding to the oxidation of COOH* on the Pt ring electrode are clearly observed by the electrochemical analysis methods. The high selectivity of CO generation from the CO2ER on the Pd/XC72 catalyst is attributed to the progressive adsorption of CO which inhibits the participation of Hads during the CO2ER.
Power-Minimization-Based Jamming Spectral Design for Finite-Duration Random Target in Clutter
Authors: Gao Jing , Wu Rihan , Guan Xin , Yu Hao , Wang Xishi
Published: May 2021

An approach to optimize the transmitted waveform of a smart jammer was developed. This study aims to improve power-saving performance by minimizing the total jamming power and allowing the values of signal-to-interference-plus-noise ratio (SINR) and mutual information (MI) between the radar return and target impulse response to be below specific thresholds. First, the model of a finite-duration random target was proposed, and the power-minimization-based optimal jamming waveform design methods in clutter with SINR and MI limitations were investigated. Subsequently, considering the impossibility of obtaining precise prior information for estimation in practice, the spectra are assumed to lie within an uncertainty class where the upper and lower bounds of each frequency point sample are known. Consequently, power-minimization-based single- and double-robust jamming waveform design methods were researched, which bound the worst power-saving performance of the jammer. Finally, we provided several numerical examples to demonstrate that the power-saving performance of smart jammers can be enhanced by employing power-minimization-based optimization algorithms.
Zataria multiflora and Pioglitazone Affect Systemic Inflammation and Oxidative Stress Induced by Inhaled Paraquat in Rats
Authors: Amin Fatemeh , Memarzia Arghavan , Roohbakhsh Ali , Shakeri Farzaneh , Boskabady Mohammad Hossein
Published: May 2021

The effects of Zataria multiflora (Z. multiflora) and pioglitazone (a PPAR-γ agonist) alone and in combination, on systemic inflammation and oxidative stress induced by inhaled paraquat (PQ) as a herbicide, which induced inflammation in rats, were examined. Rats were exposed to (1) saline (control) and (2) 54 mg/m3 PQ aerosols (8 times, every other day, each time for 30 min) without treatment or treated with (3 and 4) two doses of Z. multiflora (200 and 800 mg/kg/day), (5 and 6) two doses of pioglitazone (5 and 10 mg/kg/day), (7) low doses of

Z
.
m
u
l
t
i
f
l
o
r
a
+
pioglitazone

, (Pio-5+Z-200 mg/kg/day) or (8) dexamethasone (0.03 mg/kg/day) for 16 days, after the last PQ exposure. Different variables were measured at the end of the treatment period. Exposure to PQ significantly increased total and differential white blood cells (WBC) counts, serum levels of nitrite (NO2), malondialdehyde (MDA), interleukin- (IL) 17, and tumor necrosis factor alpha (TNF-α), but reduced thiol, superoxide dismutase (SOD), catalase (CAT), IL-10, and interferon-gamma (INF-γ) (

p
<
0.05

to

p
<
0.001

). Most measured parameters were significantly improved in groups treated with either doses of the extract, pioglitazone, Pio-5+Z-200 mg/kg/day, or dexamethasone compared to the PQ group (

p
<
0.05

to

p
<
0.001

). The combination of low doses of Pio-5+Z-200 mg/kg/day showed significantly higher effects compared to each one alone (

p
<
0.05

to

p
<
0.001

). Systemic oxidative stress and inflammation due to inhaled PQ were improved by Z. multiflora and pioglitazone. Higher effects of Pio-5+Z-200 mg/kg/day compared to each one alone suggest modulation of PPAR-γ receptors by the plant extract, but further studies using PPAR-γ antagonists need to be done in this regard.
Resolver Decoding Method Using Hilbert Transform and ATO
Authors: Yi Jiliang , Zhou Xuechun , Tan Huabing , Li Zhongqi
Published: May 2021

Resolvers are widely used in electric vehicles, trains, and other harsh fields because of their robustness. However, the resolver outputs two orthogonal analog signals, which make the resolver decoding either high hardware cost or poor decoding accuracy. A noise robust resolver decoding method using Hilbert transform and angle-tracking observer (ATO) is proposed in this paper. Firstly, Hilbert transform is employed to obtain the modular envelopes of resolver signals. Next, the modular envelopes are filtered, and their quadrants are recognized by the polarity relation of the resolver signals and the modular envelope extreme point. Then, the ideal demodulating signals are gained through the linearization of the envelope zero point. Finally, the improved ATO is used to obtain the rotor angle by iteratively calculating the demodulating signal. The effectiveness of the proposed method is verified by experiments under various rotor speed conditions and compared with other methods in noise immunity. The results show that the proposed method can control the decoding error within 0.5° when the SNR is 30 dB, which provides a high-precision and low-cost decoding scheme for practical applications.
Therapeutic Efficacy of Aerobic Exercise Training along with Oak Husk Hydroalcoholic Extract for Amelioration of Inflammation in Obese Elderly Male Mice
Authors: Zakavi Iman , Nayebifar Shila , Ghasemi Elham , Valipour Aliasghar
Published: May 2021

Background. Fibrinogen and interleukin‐1β as a proinflammatory cytokine and interleukin‐10 and nesfatin‐1 as an anti‐inflammatory cytokine have an important role in the development and prevention of systemic inflammation and incidence of obesity‐induced diseases. Thus, this study is aimed at the interaction effects of aerobic training and oak husk hydroalcoholic extract consumption on plasma levels of fibrinogen, interleukin‐1β, nesfatin‐1, and interleukin‐10 in obese elderly male mice. Materials and Methods. In this experimental study, 40 fat male mice were fed a high‐fat diet for 4 weeks to induce obesity, and subsequently, they were divided randomly into four groups: control, supplement, exercise‐placebo, and exercise‐supplement. The training groups performed aerobic exercise 5 days a week for 6 weeks (approximately 80‐75% ). The supplement groups received a solution of oak husk hydroalcoholic extract at a dose of 20 milligram per kilogram of body weight for 6 weeks. Blood samples were taken 48 h after the last training session, and the levels of IL‐10, fibrinogen, IL‐1β, and nesfatin‐1 were measured. Data were analyzed using one‐way ANOVA and LSD post hoc tests. Results. The results showed that six‐week training and oak husk hydroalcoholic extract consumption significantly increased the levels of IL‐10 and nesfatin‐1 in experimental groups (P < 0.001). Also, the levels of fibrinogen and IL‐1β decreased significantly in training groups. Averages between group variations of all indicators were statistically significant, and they were more meaningfully pronounced in the exercise‐supplement group than other groups (P ≤ 0.05). Conclusions. Considering the results of the present study, the use of moderate aerobic exercise and oak husk hydroalcoholic extract is recommended to reduce the risk of obesity; it may also have a positive effect on inflammatory factors.
Effects of Solvents on Total Phenolic Content and Antioxidant Activity of Ginger Extracts
Authors: Ezez Dessie , Tefera Molla
Published: May 2021

Ginger (Zingiber officinale) is a popular spice which is used for the treatment of different gastrointestinal and inflammatory discomfort. In the present study, the total phenolic content (TPC) and antioxidant activity of ginger extract using four solvents (ethanol, methanol, acetone, and ethyl acetate) were determined. Among the four solvents, methanol extract showed the maximum phenolic content (1183.813 mg GAE/100 g at Ayikel and 1022.409 mg GAE/100 g at Mandura) and the least phenolic content was found in acetone extract (748.865 mg GAE/100 g at Ayikel and 690.152 mg GAE/100 g at Mandura). In addition, the highest DPPH radical scavenging activity (84.868% at Ayikel and 82.883% at Mandura) was observed in methanol. However, acetone showed the least DPPH radical scavenging activity (73.864% at Ayikel and 70.597% at Mandura). Antioxidant activities of ginger extracts were also expressed as IC50 values, and acetone extract has maximum IC50 value (0.654 and 0.812 mg/mL) followed by ethyl acetate and ethanol, while being the lowest for methanol (0.481 and 0.525 mg/mL). The result of this study showed that extraction solvents significantly affected the total phenolic content and antioxidant activities of ginger. Thus, ginger can be regarded as promising candidates for natural sources of antioxidants with a high value of phenolic contents.
Short-Term Forecasting of Agriculture Commodities in Context of Indian Market for Sustainable Agriculture by Using the Artificial Neural Network
Authors: Mahto Anil Kumar , Alam M. Afshar , Biswas Ranjit , Ahmed Jawed , Alam Shah Imran
Published: May 2021

Prediction of well-grounded market information, particularly short-term forecast of prices of agricultural commodities, is the essential requirement for the sustainable development of the farming community. Such predictions are mostly performed with the help of time series models. In this study, the soft computing method is used for short-term forecasting of agriculture commodity price based on time series data using the artificial neural network (ANN). The time series data for sunflower seed and soybean seed are considered as the agriculture commodities. The soybean seed time series data were collected for the period of five years (Jan 2014–Dec 2018), for Akola district market, Maharashtra, India. The sunflower time series data were collected for the period of six years (Jan 2011–Dec 2016), for Kadari district market, Andhra Pradesh, India. The dataset is available at the Indian government website taken from the website www.data.gov.in. For forecasting, the ANN model is used on the abovementioned datasets. The performance of the model is compared with the result of the traditional ARIMA model. The mean absolute percentage error (MAPE) and root mean square percentage error (RMSPE) are considered as the performance parameters for the forecasting model. It is observed that the ANN is a better forecasting model than the ARIMA model by considering the two forecasting performance parameters MAPE and RMSPE.
Forgotten Index of Generalized Operations on Graphs
Authors: Javaid Muhammad , Javed Saira , Memon Saima Q. , Alanazi Abdulaziz Mohammed
Published: May 2021

In theoretical chemistry, several distance-based, degree-based, and counting polynomial-related topological indices (TIs) are used to investigate the different chemical and structural properties of the molecular graphs. Furtula and Gutman redefined the

F

-index as the sum of cubes of degrees of the vertices of the molecular graphs to study the different properties of their structure-dependency. In this paper, we compute

F

-index of generalized sum graphs in terms of various TIs of their factor graphs, where generalized sum graphs are obtained by using four generalized subdivision-related operations and the strong product of graphs. We have analyzed our results through the numerical tables and the graphical presentations for the particular generalized sum graphs constructed with the help of path (alkane) graphs.
Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution
Authors: Venkatesan Subramanian , Angelova Mihaela , Puttick Clare , Zhai Haoran , Caswell Deborah R. , Lu Wei-Ting , Dietzen Michelle , Galanos Panagiotis , Evangelou Konstantinos , Bellelli Roberto , Lim Emilia L. , Watkins Thomas B.K. , Rowan Andrew , Teixeira Vitor H. , Zhao Yue , Chen Haiquan , Ngo Bryan , Zalmas Lykourgos-Panagiotis , Al Bakir Maise , Hobor Sebastijan , Grönroos Eva , Pennycuick Adam , Nigro Ersilia , Campbell Brittany B. , Brown William L. , Akarca Ayse U. , Marafioti Teresa , Wu Mary Y. , Howell Michael , Boulton Simon J. , Bertoli Cosetta , Fenton Tim R. , de Bruin Robertus A.M. , Maya-Mendoza Apolinar , Santoni-Rugiu Eric , Hynds Robert E. , Gorgoulis Vassilis G. , Jamal-Hanjani Mariam , McGranahan Nicholas , Harris Reuben S. , Janes Sam M. , Bartkova Jirina , Bakhoum Samuel F. , Bartek Jiri , Kanu Nnennaya , Swanton Charles
Published: May 2021

APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast ductal carcinoma in situ, and in preinvasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx preinvasive to invasive non–small cell lung cancer (NSCLC) lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in preinvasive disease, providing fuel for selection early in cancer evolution.

Significance:

This study reveals the dynamics and drivers of APOBEC3 gene expression in preinvasive disease and the exacerbation of cellular diversity by APOBEC3B through DNA replication stress to promote chromosomal instability early in cancer evolution.

This article is highlighted in the In This Issue feature, p. 2355
Cholangiocarcinoma Risk Factors Open the Floodgates for Gut Microbes and Immunosuppressive Myeloid Cells
Authors: Chagani Sharmeen , Kwong Lawrence N.
Published: May 2021

Primary sclerosing cholangitis and colitis are known predisposing factors for bile duct cancer, but their exact pro-oncogenic mechanisms are unclear. In this issue of Cancer Discovery, Zhang and colleagues identify intestinal barrier impairment as a key mechanism, resulting in gut microbes spilling into the portal vein, in turn recruiting immunosuppressive myeloid-derived suppressor cells and promoting cholangiocarcinoma.

See related article by Zhang et al. p. 1248.
Application of Cellular Resolution Full-Field Optical Coherence Tomography in vivo for the Diagnosis of Skin Tumours and Inflammatory Skin Diseases: A Pilot Study
Authors: Wang Yen-Jen , Wang Jen-Yu , Wu Yu-Hung
Published: May 2021

Background: Optical coherence tomography (OCT) has been shown to provide non-invasive diagnosis of common skin neoplasms, especially basal cell carcinoma. OCT produces a cross-sectional view of the tissue, similar to a traditionally sectioned histopathological view, but the resolution of conventional OCT is low and thus limits clinical application. Objectives: This study aimed to investigate the application ability of a full-field (FF)OCT system which was newly developed to scan the skin at the cellular level. Methods: Patients with skin tumours or inflammatory lesions warranting biopsy were consecutively enrolled. All lesions underwent clinical, dermoscopic, and OCT assessment, followed by routine biopsy. The adjacent normal skin was scanned for comparison. OCT images were interpreted (blinded to the biopsy results) and then compared with the histopathological diagnosis. Results: A total of 111 patients with 115 lesions completed the protocol, including 80 skin tumours, 28 inflammatory diseases, and 7 other diseases. Of the OCT images, 43.5% were of good quality and show expected features. Identifiable features of actinic keratosis, Bowen’s disease, basal cell carcinoma, extramammary Paget’s disease, seborrheic keratosis, large cell acanthoma, bullous pemphigoid, interface dermatitis, lichenoid tissue reaction, and psoriasis were demonstrated. Lesions are located deeply, and so some features were out of the field of view, accounting for 40.0% (46/115). Conclusions: This study expanded the ability of FFOCT for the clinical diagnosis of various skin conditions. This new optical technique can clearly visualise skin lesions located in the epidermis and upper dermis. It provided an effective way to perform digital skin biopsy in superficial skin diseases.
Clinical Characteristics of Chinese Male Patients with Aquaporin-4 Antibody-Positive Late-Onset Neuromyelitis Optica Spectrum Disorder
Authors: Liang Jie , Liu Jia , Gu Meifeng , Zhu Cansheng , Xu Xiaofeng , Fan Rong , Peng Fuhua , Jiang Ying
Published: May 2021

Background and Objective: Limited studies are available for male patients with anti-aquaporin-4 antibody (AQP4-Ab)-positive late-onset neuromyelitis optica spectrum disease (LONMOSD). The aim of this study was to investigate the clinical characteristics of Chinese male patients with AQP4-Ab-positive LONMOSD. Methods: We retrospectively reviewed the medical records of 12 male patients with LONMOSD, 16 male patients with early-onset NMOSD (EONMOSD), and 64 female patients with LONMOSD. These enrolled patients were classified according to the age of onset: LONMOSD (≥50 years of age at onset) versus EONMOSD (<50 years of age at onset). Clinical characteristics and magnetic resonance imaging (MRI) findings were collected. All included patients were positive for AQP4 antibody. Results: Compared with female LONMOSD patients, male LONMOSD patients had less frequent transverse myelitis (TM) at onset (8.33 vs. 53.13%, p = 0.004) and lower Expanded Disability Status Scale (EDSS) scores (median 1 vs. 4, p = 0.036). Compared with male EONMOSD patients, male LONMOSD patients had a shorter time from onset to diagnosis (0.85 months vs. 6.00 months, p = 0.04). Conclusion: Less common TM at onset, less disease severity, and shorter time from onset to diagnosis probably occur in male LONMOSD patients.
Retrospective Analysis of the Clinical Presentation, Treatment and Outcome of Angiosarcoma in a Sarcoma Referral Center
Authors: Schöffski Patrick , Timmermans Iris , Wildiers Hans , Dumez Herlinde , Hompes Daphne , Christiaens Melissa , Sciot Raf , Laenen Annouschka , Lee Che-Jui , Meyskens Thomas
Published: May 2021

Introduction: Angiosarcoma (AS) is a rare subtype of soft tissue sarcoma. We performed a retrospective analysis of patient characteristics, treatments and prognostic factors in patients treated in a single sarcoma center. Methods: We reviewed records of patients treated between 1987 and 2018, categorized in 7 different subtypes according to tissue of origin and underlying risk factors. The Kaplan-Meier method was used to estimate overall survival (OS); the Cox proportional hazards model was used to study prognostic variables. Results: Among 134 patients, 30% had radiation-induced, 31% primary soft tissue, 24% cutaneous, 5% breast, 4% bone, 2% lymphedema-associated and 4% unknown primary AS. Key patient/disease characteristics varied between subgroups. The median OS was 22.0 months for the entire cohort, with 28.9% with a 5-year survival. Metastasis at diagnosis was seen in 23% of patients; 38% developed metachronous metastasis. Sixty-six (49%) patients received systemic therapy; common first-line treatments were doxorubicin (48%) and paclitaxel (39%), without a significant difference in OS between agents. Younger age, breast/radiation-induced AS, primary surgery and palliative chemotherapy were associated with better OS. Synchronous metastasis, soft tissue/unknown primary location correlated with poor survival. Conclusion: AS is a very heterogeneous sarcoma subtype, with substantial variability in clinical presentation and survival among patient subsets. Prognosis is poor, and there is no difference in outcome comparing the 2 most frequently used chemotherapy agents in the first line, paclitaxel and doxorubicin.
Chronic Constipation: Gastroenterohepatologist’s Approach
Authors: Milosavljevic Tomica , Popovic Dusan D. , Mijac Dragana Danilo , Milovanovic Tamara , Krstic Slobodan , Krstic Miodrag N.
Published: May 2021

Background: Constipation is a common problem in gastroenterological practice. The prevalence of constipation is about 16%. Constipation can be primary or secondary. Summary: The diagnostic and therapeutic approach to patients with constipation begins with a detailed history and physical examination. In selected cases, the use of additional diagnostic procedures is very important. This includes the use of laboratory, endoscopic, and radiological examinations, as well as advanced physiological testing (anorectal manometry, balloon expulsion test, colonic transit studies, and defecography). Constipation therapy can be both nonoperative and operative. Nonoperative therapy includes the application of a lifestyle measures, pharmacotherapy and biofeedback therapy. Key Messages: Two key things when taking a medical history and physical examination are to rule out the existence of alarm symptoms/signs and to rule out secondary constipation (primarily drug-induced). Therapy begins with lifestyle modification, and in case of failure, bulk or osmotic laxatives are used. In case of failure, the use of lubiprostone is indicated, as well as linaclotide. Surgical treatment of constipation is reserved for cases of refractory constipation, with delayed intestinal transit.
proposta pedagógica de leitura de imagens em manuais de língua portuguesa do ensino médio
Authors: Pereira Hylo Leal , Araújo Antônia Dilamar
Published: May 2021

O presente artigo propõe uma reflexão sobre o trabalho com imagens constante na subseção Leitura da imagem, presente na coleção Português: contexto, interlocução e sentido, obra integrante do PNLD de 2018, com o intuito de aproximar concepções teóricas atuais relacionadas aos multiletramentos ao fazer pedagógico proposto para o professor de Língua Portuguesa no referido manual de ensino. Acrescentam-se a esse excurso teórico contribuições advindas da multimodalidade, do letramento visual e do letramento crítico. A pesquisa caracteriza-se por uma abordagem qualitativa e analisa duas das oito atividades presentes no terceiro volume da referida coleção. Conclui-se que há lacunas relativas ao trabalho com as teorias dos multiletramentos que, se preenchidas, tendem a potencializar as competências textuais relativas ao adequado letramento visual e crítico dos estudantes.
Audiências de conciliação: determinações legais e interação
Authors: Galvão Marise Adriana Mamede , Lanzillo Anderson Souza da Silva
Published: May 2021

Este estudo é uma reflexão direcionada à interação em audiências de conciliação realizadas em um Fórum Cível no Estado do Rio Grande do Norte.  Buscamos discutir algumas dimensões dessas audiências, guiados pelo que define a legislação (Código de Processo Civil e Lei dos Juizados Especiais), observando de que forma as regulações normativas influenciam os aspectos linguístico-discursivos. Nesse sentido, privilegiamos as evidências da organização geral da interação e as escolhas lexicais que permeiam as audiências, do ponto de vista da Conversação Institucional.  Seguimos a orientação da Análise da Conversação para a construção do corpus de investigação, constituído por duas audiências de conciliação gravadas em vídeo e transcritas conforme o sistema adotado pelos estudos de textos orais. A análise dos dados das audiências nos possibilitou reconhecer algumas regularidades na interação, marcadas pelo que é definido institucionalmente, haja vista o cumprimento de leis e orientações que se manifestam no plano linguístico-discursivo, a partir do léxico identificado nos dados da presente pesquisa.
Apresentação - Celso Furtado, transdisciplinar e contemporâneo
Authors: Barbosa Alexandre , Botelho André , Cepêda Vera , Saes Alexandre
Published: May 2021

Apresentação do Dossiê Celso Furtado, transdisciplinar e contemporâneo
Leituras em competição (à distância)
Authors: Brasil Junior Antonio , Carvalho Lucas , Helayel Karim
Published: May 2021

O impacto da obra de Celso Furtado e a disponibilidade de uma imensa quantidade de dados que permitem mensurar os padrões da produção científica levaram à proposição de dois experimentos de pesquisa. O primeiro, uma exploração cientométrica das bases Web of Science e SciELO, procurou detectar os principais temas e áreas de pesquisa que interagem com os textos de Furtado. O segundo, uma análise do fluxo de visitas entre os verbetes da Wikipédia dedicados ao economista paraibano em diferentes idiomas, pretendeu cartografar as principais controvérsias “públicas” quanto ao seu legado.
Volta às fontes batismais
Authors: Barboza Darlan , Ribas Elisabete
Published: May 2021

O presente artigo pretende ilustrar e discutir, a partir de documentos selecionados do arquivo pessoal de Celso Furtado, doado em 2019 ao Instituto de Estudos Brasileiros (IEB), duas facetas da trajetória profissional de seu titular: a atuação no contexto da criação e da gestão da Sudene e o papel que teve como formador e inspirador da juventude de sua época. Espera-se que esta breve exposição estimule o interesse de outros pesquisadores pelo acervo de Celso Furtado, composto de milhares de itens que exprimem uma vida e uma obra dedicadas a pensar e transformar o Brasil.
Celso Furtado
Authors: Klüger Elisa
Published: May 2021

Este artigo reconstrói a trajetória de Celso Furtado até o início dos anos 1960 e analisa escritos nos quais ele define a visão de ciência econômica que norteia sua atuação em um país subdesenvolvido. Furtado sustenta que a economia não é neutra e universal, ressaltando a necessidade de produzir conhecimentos historicamente situados e de estabelecer coletivamente as finalidades das intervenções econômicas. Argumenta-se que a ciência econômica professada por Furtado é iconoclasta, ao romper com os paradigmas neoclássicos, e inconformista, ao visar à transformação da realidade social.
Needs of patients in palliative care from the perspective of family members
Authors: Novak Valentina , Ovčina Amer , Neuberg Marijana , Cikač Tina
Published: May 2021

Introduction: Every person is a multidimensional being and certain needs
arise from each dimension. In palliative care, the emphasis is on alleviating the
physical, emotional, spiritual, and social needs of patients through a holistic
approach. The aim of the study was to determine how family members recognize
and experience the needs of their family members who are in palliative care.
Methods: A qualitative research method was used. Data were obtained through
interviews. Coding determined categories and codes that were later linked
into grounded theory. For the purposes of the research, a semi-structured interview
was conducted via the Google Meet application. The study involved 4
participants.
Results: The analysis of the interviews defined four categories that talk about
the segments of holistic care: physical, psychological, social and spiritual needs.
The presented codes are supported by the statements of the participants.
Discussion: Family members of patients in palliative care recognize the needs
arising from all four dimensions of human – physical, psychological, social and
spiritual needs, but in practice, the emphasis is still on caring for physical needs.
Conclusion: The best results of palliative care are recognized in taking care of
the physical needs of patients, especially pain, but more effort should be made
in educating nurses and organizing changes to completely implement holistic
nursing care in which psychological, social and spiritual needs are also taken
care of
Particulate Air Pollution and Risk of Cardiovascular Events Among Adults With a History of Stroke or Acute Myocardial Infarction
Authors: Liao Noelle S. , Sidney Stephen , Deosaransingh Kamala , Van Den Eeden Stephen K. , Schwartz Joel , Alexeeff Stacey E.
Published: May 2021

Background

Previous studies have found associations between fine particulate matter <2.5 µm in diameter (PM
2.5
) and increased risk of cardiovascular disease (CVD) among populations with no CVD history. Less is understood about susceptibility of adults with a history of CVD and subsequent PM
2.5
‐related CVD events and whether current regulation levels for PM
2.5
are protective for this population.

Methods and Results

This retrospective cohort study included 96 582 Kaiser Permanente Northern California adults with a history of stroke or acute myocardial infarction. Outcome, covariate, and address data obtained from electronic health records were linked to time‐varying 1‐year mean PM
2.5
exposure estimates based on residential locations. Cox proportional hazard models estimated risks of stroke, acute myocardial infarction, and cardiovascular mortality associated with PM
2.5
exposure, adjusting for multiple covariates. Secondary analyses estimated risks below federal and state regulation levels (12 µg/m
3
for 1‐year mean PM
2.5
). A 10‐µg/m
3
increase in 1‐year mean PM
2.5
exposure was associated with an increase in risk of cardiovascular mortality (hazard ratio [HR], 1.20; 95% CI, 1.11–1.30), but no increase in risk of stroke or acute myocardial infarction. Analyses of <12 µg/m
3
showed increased risk for CVD mortality (HR, 2.31; 95% CI, 1.96–2.71), stroke (HR, 1.41; 95% CI, 1.09–1.83]), and acute myocardial infarction (HR, 1.51; 95% CI, 1.21–1.89) per 10‐µg/m
3
increase in 1‐year mean PM
2.5
.

Conclusions

Adults with a history of CVD are susceptible to the effects of PM
2.5
exposure, particularly on CVD mortality. Increased risks observed at exposure levels <12 µg/m
3
highlight that current PM
2.5
regulation levels may not be protective for this susceptible population.
Race Differences in High-Grade Carotid Artery Stenosis
Authors: Lal Brajesh K. , Meschia James F. , Brott Thomas G. , Jones Michael , Aronow Herbert D. , Lackey Angelica , Howard George
Published: May 2021

Background and Purpose:

Despite a higher incidence of stroke and a more adverse cardiovascular risk factor profile in Blacks and Hispanics compared with Whites, carotid artery revascularization is performed less frequently among these subpopulations. We assessed racial differences in high-grade (≥70% diameter-reducing) carotid stenosis.

Methods:

Consecutive clients in a Nationwide Life Line for-Profit Service to screen for vascular disease, 2005 to 2019 were evaluated in a cross-sectional study. The prevalence of high-grade stenosis, defined by a carotid ultrasound peak systolic velocity of ≥230 cm/s, was assessed. Participants self-identified as White, Black, Hispanic, Asian, Native American, or other. Race/ethnic differences were assessed using Poisson regression. The number of individuals in the United States with high-grade stenosis was estimated by applying prevalence estimates to 2015 US Census population estimates.

Results:

The prevalence of high-grade carotid stenosis was estimated in 6 130 481 individuals. The prevalence of high-grade stenosis was higher with increasing age in all race-sex strata. Generally, Blacks and Hispanics had a lower prevalence of high-grade stenosis compared with Whites, while Native Americans had a higher prevalence. For example, for men aged 55 to 65, the relative risk of stenosis compared with Whites was 0.40 (95% CI, 0.29–0.55) and 0.61 (95% CI, 0.46–0.81) for Blacks and Hispanics, respectively; and 1.53 (95% CI, 1.12–2.10) for Native Americans. When these prevalence estimates were applied to the Census estimates of the US population, an estimated 327 721 individuals have high-grade stenosis, of whom 7% are Black, 7% Hispanic, and 43% women.

Conclusions:

Despite their having a more adverse cardiovascular risk profile, there was a lower prevalence of high-grade carotid artery stenosis for both the Black and Hispanic relative to the White clients. This lower prevalence of high-grade stenosis is a potential contributor to the lower use of carotid revascularization procedures in these minority populations.