bluuebunny/crossref_metadata_2025 huggingface dataset:
DLDTI: a learning-based framework for drug-target interaction identification using neural networks and network representation
Authors: Zhao Yihan , Zheng Kai , Guan Baoyi , Guo Mengmeng , Song Lei , Gao Jie , Qu Hua , Wang Yuhui , Shi Dazhuo , Zhang Ying
Published: November 2020

Background

Drug repositioning, the strategy of unveiling novel targets of existing drugs could reduce costs and accelerate the pace of drug development. To elucidate the novel molecular mechanism of known drugs, considering the long time and high cost of experimental determination, the efficient and feasible computational methods to predict the potential associations between drugs and targets are of great aid.

Methods

A novel calculation model for drug-target interaction (DTI) prediction based on network representation learning and convolutional neural networks, called DLDTI, was generated. The proposed approach simultaneously fused the topology of complex networks and diverse information from heterogeneous data sources, and coped with the noisy, incomplete, and high-dimensional nature of large-scale biological data by learning the low-dimensional and rich depth features of drugs and proteins. The low-dimensional feature vectors were used to train DLDTI to obtain the optimal mapping space and to infer new DTIs by ranking candidates according to their proximity to the optimal mapping space. More specifically, based on the results from the DLDTI, we experimentally validated the predicted targets of tetramethylpyrazine (TMPZ) on atherosclerosis progression in vivo.

Results

The experimental results showed that the DLDTI model achieved promising performance under fivefold cross-validations with AUC values of 0.9172, which was higher than the methods using different classifiers or different feature combination methods mentioned in this paper. For the validation study of TMPZ on atherosclerosis, a total of 288 targets were identified and 190 of them were involved in platelet activation. The pathway analysis indicated signaling pathways, namely PI3K/Akt, cAMP and calcium pathways might be the potential targets. Effects and molecular mechanism of TMPZ on atherosclerosis were experimentally confirmed in animal models.

Conclusions

DLDTI model can serve as a useful tool to provide promising DTI candidates for experimental validation. Based on the predicted results of DLDTI model, we found TMPZ could attenuate atherosclerosis by inhibiting signal transductions in platelets. The source code and datasets explored in this work are available at https://github.com/CUMTzackGit/DLDTI.
Combining epigenetic and clinicopathological variables improves specificity in prognostic prediction in clear cell renal cell carcinoma
Authors: Andersson-Evelönn Emma , Vidman Linda , Källberg David , Landfors Mattias , Liu Xijia , Ljungberg Börje , Hultdin Magnus , Rydén Patrik , Degerman Sofie
Published: November 2020

Background

Metastasized clear cell renal cell carcinoma (ccRCC) is associated with a poor prognosis. Almost one-third of patients with non-metastatic tumors at diagnosis will later progress with metastatic disease. These patients need to be identified already at diagnosis, to undertake closer follow up and/or adjuvant treatment. Today, clinicopathological variables are used to risk classify patients, but molecular biomarkers are needed to improve risk classification to identify the high-risk patients which will benefit most from modern adjuvant therapies. Interestingly, DNA methylation profiling has emerged as a promising prognostic biomarker in ccRCC. This study aimed to derive a model for prediction of tumor progression after nephrectomy in non-metastatic ccRCC by combining DNA methylation profiling with clinicopathological variables.

Methods

A novel cluster analysis approach (Directed Cluster Analysis) was used to identify molecular biomarkers from genome-wide methylation array data. These novel DNA methylation biomarkers, together with previously identified CpG-site biomarkers and clinicopathological variables, were used to derive predictive classifiers for tumor progression.

Results

The “triple classifier” which included both novel and previously identified DNA methylation biomarkers together with clinicopathological variables predicted tumor progression more accurately than the currently used Mayo scoring system, by increasing the specificity from 50% in Mayo to 64% in our triple classifier at 85% fixed sensitivity. The cumulative incidence of progress (pCIP5yr) was 7.5% in low-risk vs 44.7% in high-risk in M0 patients classified by the triple classifier at diagnosis.

Conclusions

The triple classifier panel that combines clinicopathological variables with genome-wide methylation data has the potential to improve specificity in prognosis prediction for patients with non-metastatic ccRCC.
Effects of virtual reality training on occupational performance and self-efficacy of patients with stroke: a randomized controlled trial
Authors: Long Yi , Ouyang Rang-ge , Zhang Jia-qi
Published: November 2020

Background

Virtual reality (VR) has been broadly applied in post-stroke rehabilitation. However, studies on occupational performance and self-efficacy as primary outcomes of stroke rehabilitation using VR are lacking. Thus, this study aims to investigate the effects of VR training on occupational performance and self-efficacy in patients with stroke.

Methods

This was an assessor-blinded, randomized controlled trial. Sixty participants with first-ever stroke (< 1-year onset) underwent rehabilitation in a single acute hospital. Participants were randomly assigned to either the VR group (n = 30) or control group (n = 30). Both groups received dose-matched conventional rehabilitation (i.e., 45 min, five times per week over 3 weeks). The VR group received additional 45-min VR training for five weekdays over 3 weeks. The primary outcome measures were the Canadian Occupational Performance Measure and Stroke Self-Efficacy Questionnaire. Secondary outcome measures included Modified Barthel Index, Fugl-Meyer Assessment-Upper Extremity, and Functional Test for the Hemiplegic Upper Extremity. The assessment was conducted at baseline and after the 3-week intervention.

Results

A total of 52 participants (86.7%) completed the trial. Significant between-group differences in Stroke Self-Efficacy Questionnaire (Median Difference = 8, P = 0.043) and Modified Barthel Index (Median Difference = 10, P = 0.030) were found; however, no significant between-group differences in Canadian Occupational Performance Measure, Fugl-Meyer Assessment-Upper Extremity, and Functional Test for the Hemiplegic Upper Extremity were noted. No serious adverse reactions related to the program were reported.

Conclusions

Additional VR training could help improve the self-efficacy and activities of daily living of patients with stroke; however, it was not superior to conventional training in the improvement of upper limb functions, occupational performance, and satisfaction. Nevertheless, VR could be integrated into conventional rehabilitation programs to enhance self-efficacy of patients after stroke.

Trial registration

This study was successfully registered under the title “Effects of virtual reality training on occupational performance and self-efficacy of patients with stroke” on October 13 2019 and could be located in https://www.chictr.org with the study identifier ChiCTR1900026550.
Seroprevalence and genotypic characterization of HBV among low risk voluntary blood donors in Nairobi, Kenya
Authors: Aluora Patrick Okoti , Muturi Margaret Wangui , Gachara George
Published: November 2020

Background

Hepatitis B virus (HBV) causes significant morbidity and mortality globally primarily due to its ability to cause hepatitis, liver cirrhosis and hepatocellular carcinoma. The Kenya National Blood Transfusion Services screens for Hepatitis B antibodies using the chemiluminescent microparticle immunoassay method. This test does not inform on the genotypic characteristics of the virus or the actual presence of the virus in blood. This study therefore sought to determine the serologic and genotypic profiles of HBV circulating among the voluntary blood donors in Nairobi.

Methods

Blood samples were collected in plain and EDTA vacutainers and tested for the Hepatitis B surface antigen (HBsAg). HBV DNA was then extracted from plasma, its overlapping P/S gene amplified and sequenced. The resulting sequences were used to analyze for the circulating genotypes and mutations within the P and S genes. Bivariate statistical analysis was used to determine the association between demographic factors and HBV infection.

Results

A seroprevalence of 2.3% (n = 7) was reported. The age group 19–28 years was significantly associated with HBV infection. Nine samples were positive for HBV DNA; these included 2 HBsAg positive samples and 7 HBsAg negative samples. Genotype A, sub genotype A1 was found to be exclusively prevalent while a number of mutations were reported in the “a” determinant segment of the major hydrophilic region of the S gene associated with antibody escape. RT mutations including mutation rt181T in the P gene conferring resistance against Lamivudine and other ʟ-nucleoside drugs were detected.

Conclusion

There is a high prevalence of occult HBV infections among these blood donors and therefore the testing platform currently in use requires revision.
Rapid SARS-CoV-2 antigen detection assay in comparison with real-time RT-PCR assay for laboratory diagnosis of COVID-19 in Thailand
Authors: Chaimayo Chutikarn , Kaewnaphan Bualan , Tanlieng Nattaya , Athipanyasilp Niracha , Sirijatuphat Rujipas , Chayakulkeeree Methee , Angkasekwinai Nasikarn , Sutthent Ruengpung , Puangpunngam Nattawut , Tharmviboonsri Theerawoot , Pongraweewan Orawan , Chuthapisith Suebwong , Sirivatanauksorn Yongyut , Kantakamalakul Wannee , Horthongkham Navin
Published: November 2020

Background

The Coronavirus disease 2019 (COVID-19) pandemic continues to spread across the world. Hence, there is an urgent need for rapid, simple, and accurate tests to diagnose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Performance characteristics of the rapid SARS-CoV-2 antigen detection test should be evaluated and compared with the gold standard real-time reverse transcription-polymerase chain reaction (RT-PCR) test for diagnosis of COVID-19 cases.

Methods

The rapid SARS-CoV-2 antigen detection test, Standard™ Q COVID-19 Ag kit (SD Biosensor®, Republic of Korea), was compared with the real-time RT-PCR test, Allplex™ 2019-nCoV Assay (Seegene®, Korea) for detection of SARS-CoV-2 in respiratory specimens. Four hundred fifty-four respiratory samples (mainly nasopharyngeal and throat swabs) were obtained from COVID-19 suspected cases and contact individuals, including pre-operative patients at Siriraj Hospital, Bangkok, Thailand during March–May 2020.

Results

Of 454 respiratory samples, 60 (13.2%) were positive, and 394 (86.8%) were negative for SARS-CoV-2 RNA by real-time RT-PCR assay. The duration from onset to laboratory test in COVID-19 suspected cases and contact individuals ranged from 0 to 14 days with a median of 3 days. The rapid SARS-CoV-2 antigen detection test’s sensitivity and specificity were 98.33% (95% CI, 91.06–99.96%) and 98.73% (95% CI, 97.06–99.59%), respectively. One false negative test result was from a sample with a high real-time RT-PCR cycle threshold (Ct), while five false positive test results were from specimens of pre-operative patients.

Conclusions

The rapid assay for SARS-CoV-2 antigen detection showed comparable sensitivity and specificity with the real-time RT-PCR assay. Thus, there is a potential use of this rapid and simple SARS-CoV-2 antigen detection test as a screening assay.
Effect of manual reduction and indirect decompression on thoracolumbar burst fracture: a comparison study
Authors: Huang Jian , Zhou Limin , Yan Zhaodong , Zhou Zongbo , Gou Xuejian
Published: November 2020

Objective

To evaluate the effect of manual reduction and indirect decompression on thoracolumbar burst fracture.

Methods

Sixty patients with thoracolumbar burst fracture who were hospitalized from January 2018 to October 2019 were selected and divided into an experimental group (33 cases) and control group (27 cases) according to different treatment methods. The experimental group was treated with manual reduction and indirect decompression, while the control group was not treated with manual reduction. The operation time and intraoperative blood loss were recorded. VAS score was used to evaluate the improvement of pain. The anterior height of the injured vertebra, wedge angle of the injured vertebral body, and encroachment ratio of the injured vertebral canal were used to evaluate the spinal canal decompression and fracture reduction. JOA score was used to evaluate the improvement of spinal function.

Results

There was no significant difference in operation time and intraoperative blood loss between the two groups. Compared with the control group, the VAS score and the wedge angle of the injured vertebral body of the experimental group 3 days after the operation and the last follow-up were significantly lower than that of the control group, and the difference was statistically significant. The ratio of the anterior height of the injured vertebra of the experimental group 3 days after the operation and the last follow-up was significantly higher than that of the control group, and the difference was statistically significant. The difference of the encroachment ratio of the injured vertebral canal between preoperation and 3 days after operation was significantly higher than that of the control group, and the difference was statistically significant. The bladder function of JOA 3 days after the operation of the experimental group was significantly higher than that of the control group, and the difference was statistically significant. And the rest aspect of JOA on 3 days after the operation and last follow-up of the experimental group has no significant difference compared with the control group.

Conclusion

Manipulative reduction and indirect decompression can obtain a better clinical effect in the treatment of thoracolumbar burst fractures.
Frequency and methylation status of selected retrotransposition competent L1 loci in amyotrophic lateral sclerosis
Authors: Savage Abigail L. , Lopez Ana Illera , Iacoangeli Alfredo , Bubb Vivien J. , Smith Bradley , Troakes Claire , Alahmady Nada , Koks Sulev , Schumann Gerald G. , Al-Chalabi Ammar , Quinn John P.
Published: November 2020

Long interspersed element-1 (LINE-1/L1) is the only autonomous transposable element in the human genome that currently mobilises in both germline and somatic tissues. Recent studies have identified correlations between altered retrotransposon expression and the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) in a subset of patients. The risk of an individual developing ALS is dependent on an interaction of genetic variants and subsequent modifiers during life. These modifiers could include environmental factors, which can lead to epigenetic and genomic changes, such as somatic mutations, occurring in the neuronal cells that degenerate as the disease develops. There are more than 1 million L1 copies in the human genome today, but only 80–100 L1 loci in the reference genome are considered to be retrotransposition-competent (RC) and an even smaller number of these RC-L1s loci are highly active. We hypothesise that RC-L1s could affect normal cellular function through their mutagenic potential conferred by their ability to retrotranspose in neuronal cells and through DNA damage caused by the endonuclease activity of the L1-encoded ORF2 protein. To investigate whether either an increase in the genomic burden of RC-L1s or epigenetic changes to RC-L1s altering their expression, could play a role in disease development, we chose a set of seven well characterised genomic RC-L1 loci that were reported earlier to be highly active in a cellular L1 retrotransposition reporter assay or serve as major source elements for germline and/or somatic retrotransposition events. Analysis of the insertion allele frequency of five polymorphic RC-L1s, out of the set of seven, for their presence or absence, did not identify an increased number individually or when combined in individuals with the disease. However, we did identify reduced levels of methylation of RC-L1s in the motor cortex of those individuals with both familial and sporadic ALS compared to control brains. The changes to the regulation of the loci encompassing these RC-L1s demonstrated tissue specificity and could be related to the disease process.
Comparison of loop-mediated isothermal amplification and conventional PCR tests for diagnosis of common Brucella species
Authors: Moeini-Zanjani Ali , Pournajaf Abazar , Ferdosi-Shahandashti Elaheh , Gholami Mehrdad , Masjedian Faramarz , Khafri Soraya , Rajabnia Ramazan
Published: November 2020

Objective

Rapid, reliable, and affordable detection of Brucella species via the molecular methods remains a challenge. In recent years, loop-mediated isothermal amplification (LAMP) is a functional nucleic acid amplification technique offering a substitute to polymerase chain reaction (PCR). So, we compared the LAMP assay with the conventional PCR for the identification of common Brucella species in Iran. In this study, LAMP assay was comprehensively evaluated against the common PCR method. A group of specific LAMP primers were used to amplify a highly specific fragment from the sequence of the Brucella abortus, bcsp31 gene. Sensitivity and specificity values of tests were done with a set of 78 (50 Brucella and 28 non-Brucella) strains.

Results

A dilution series of B. abortus DNA indicated that the LAMP reaction could reliably detect 10 (fg/µl) DNA target copies per reaction within 36 min, which is 10 times greater than the PCR assay. In summary, we conclude that LAMP assay provide accurate and fast test results to identify of common Brucella species in low-complexity labs, mainly in low and lower middle income countries.
Sequence spaces derived by the triple band generalized Fibonacci difference operator
Authors: Yaying Taja , Hazarika Bipan , Mohiuddine S. A. , Mursaleen M. , Ansari Khursheed J.
Published: November 2020

In this article we introduce the generalized Fibonacci difference operator$\mathsf{F}(\mathsf{B})$F(B)by the composition of a Fibonacci band matrix and a triple band matrix$\mathsf{B}(x,y,z)$B(x,y,z)and study the spaces$\ell _{k}( \mathsf{F}(\mathsf{B}))$ℓk(F(B))and$\ell _{\infty }(\mathsf{F}(\mathsf{B}))$ℓ∞(F(B)). We exhibit certain topological properties, construct a Schauder basis and determine the Köthe–Toeplitz duals of the new spaces. Furthermore, we characterize certain classes of matrix mappings from the spaces$\ell _{k}(\mathsf{F}(\mathsf{B}))$ℓk(F(B))and$\ell _{\infty }(\mathsf{F}(\mathsf{B}))$ℓ∞(F(B))to space$\mathsf{Y}\in \{\ell _{\infty },c_{0},c,\ell _{1},cs_{0},cs,bs\}$Y∈{ℓ∞,c0,c,ℓ1,cs0,cs,bs}and obtain the necessary and sufficient condition for a matrix operator to be compact from the spaces$\ell _{k}(\mathsf{F}(\mathsf{B}))$ℓk(F(B))and$\ell _{\infty }(\mathsf{F}(\mathsf{B}))$ℓ∞(F(B))to$\mathsf{Y}\in \{ \ell _{\infty }, c, c_{0}, \ell _{1},cs_{0},cs,bs\} $Y∈{ℓ∞,c,c0,ℓ1,cs0,cs,bs}using the Hausdorff measure of non-compactness.
Statistical analysis of short-wave fadeout for extreme space weather event estimation
Authors: Tao Chihiro , Nishioka Michi , Saito Susumu , Shiota Daikou , Watanabe Kyoko , Nishizuka Naoto , Tsugawa Takuya , Ishii Mamoru
Published: November 2020

Solar flares trigger an increase in plasma density in the ionosphere including the D region, and cause the absorption of radio waves, especially in high-frequency (HF) ranges, called short-wave fadeout (SWF). To evaluate the SWF duration and absorption statistically, we analyze long-term (36 years) ionosonde data observed by the National Institute of Information and Communications Technology (NICT). The minimum reflection frequency, fmin, is used to detect SWFs from 15-min-resolution ionosonde observations at Kokubunji, Tokyo, from 1981 to 2016. Since fmin varies with local time (LT) and season, we refer to dfmin, which is defined as fmin subtracted by its 27-day running median at the same LT. We find that the occurrence of SWFs detected by three criteria, (i) dfmin ≥ 2.5 MHz, (ii) dfmin ≥ 3.5 MHz, and (iii) blackout, during daytime associated with any flare(s) greater than the C1 class is maximized at local noon and decreases with increasing solar zenith angle. We confirm that the dfmin and duration of SWFs increase with the solar flare class. We estimate the absorption intensity from observations, which is comparable to an empirical relationship obtained from sudden cosmic noise absorption. A generalized empirical relationship for absorption from long-distance circuits shows quantitatively different dependences on solar flare flux, solar zenith angle, and frequency caused by different signal passes compared with that obtained from cosmic noise absorption. From our analysis and the empirical relationships, we estimate the duration of extreme events with occurrence probabilities of once per 10, 100, and 1000 years to be 1.8–3.6, 4.0–6.8, and 7.4–11.9 h, respectively. The longest duration of SWFs of about 12 h is comparable to the solar flare duration derived from an empirical relationship between the solar flare duration and the solar active area for the largest solar active region observed so far.
Intussusception caused by a small intestinal lipoma with ectopic gastric mucosa containing gastric cystica profunda component cells within the inverted Meckel’s diverticulum: a case report
Authors: Yamauchi Natsuko , Ito Takashi , Matsuoka Hiroki , Chohno Teruhiro , Hasegawa Hiroshi , Kakeji Yoshihiro , Ohnishi Takamasa
Published: November 2020

Background

Lipomas are the most common cause of intussusception in adults. To our knowledge, however, no cases of lipoma and ectopic gastric mucosa with gastritis cystica profunda (GCP) have been reported. We report a case of intussusception caused by a small intestinal lipoma with ectopic gastric mucosa containing GCP-component cells within the inverted Meckel’s diverticulum.

Case presentation

A female in her 40s underwent computed tomography for postoperative follow-up of left breast cancer. A tumor, suspected to be a lipoma, was found in the ileum. Since there were no symptoms, the patient underwent regular follow-up. However, gradual enlargement was observed, and surgery was recommended due to the risk of intussusception. After reduction via the Hutchinson technique, laparoscopically assisted partial resection of the small intestine was performed due to suspicion that the tumor was causing intussusception starting from the ileum. Histopathologic examinations revealed proliferation of mature adipose tissue in the subserosal layer, which was diagnosed as lipoma. Furthermore, adipose tissue was found in the stem area and accordingly, we diagnosed lipoma associated with the inverted Meckel’s diverticulum. Moreover, gastric mucosa-like crypt epithelium and proper glandular tissue were identified in the mucosal membrane at the area of onset, and signs of gastric pit dilatation over the submucosa and crypt epithelium hyperplasia were observed. Diagnosis was ectopic gastric mucosa containing GCP component tissue.

Conclusions

Intussusception in the small intestine complicated with lipoma and ectopic gastric mucosa with GCP within the Meckel’s diverticulum has not been reported, demonstrating the rarity of our case.
Optic coherence tomography features of subretinal vitreous substitutes
Authors: Zacharias Leandro Cabral , da Silva Neto Epitácio Dias , dos Santos Rodrigues Neto Taurino , de Carvalho Júnior José Ronaldo Lima , Preti Rony Carlos , Cunha Leonardo Provetti , Tanaka Tatiana , Monteiro Mário Luiz Ribeiro
Published: November 2020

Background

To draw comparisons between spectral domain optic coherence tomography (SD-OCT) features of subretinal silicon oil (SO), perfluoro-n-octane (PFO) or C3F8 gas.

Methods

Cases diagnosed with retained subretinal vitreous substitutes (VS) were retrospectively selected. Demographic data were collected and OCT features were analyzed.

Results

In the 13 cases with subretinal PFO, hyper-reflectivity under the bubble was noted in 8 eyes (61.5%); choroidal shadow at the borders of the bubble in 11 eyes (84.6%); hyper-reflective halo around the bubble in 5 eyes (38.4%) and a hyper-reflective apical dot in 8 eyes (61.5%).The two cases with multiple PFO bubbles had complete septum dividing the bubbles. The one case with subretinal SO had hyper reflectivity under the bubble; no choroidal shadow at the edge of the bubble; hyper-reflective halo was noted around the bubble and the apical hyper-reflective dot was present; there was no complete septum dividing multiple bubbles. The single case with subretinal C3F8had some bubbles with totally round base, incomplete septum, hyper reflectivity under the bubble, choroidal shadow at the edge of the bubble, a hyper-reflective halo and an apical dot.

Conclusion

Different subretinal VS share similar SD-OCT characteristics. Round base bubbles are only observed with subretinal C3F8 gas, while incomplete septum are related to retained subretinal SO or gas.
Doing better: eleven ways to improve the integration of sex and gender in health research proposals
Authors: Mason Robin
Published: November 2020

Background

Integrating a sex and gender lens is increasingly recognized as important in health research studies. Past failures to adequately consider sex in drug development, for example, led to medications that were metabolized differently, proved harmful, or ineffective, for females. Including both males and females in study populations is important but not sufficient; health, access to healthcare, and treatment provided are also influenced by gender, the socially mediated roles, responsibilities, and behaviors of boys, girls, women and men. Despite understanding the relevance of sex and gender to health research, integrating this lens into study designs can still be challenging. Identified here, are nine opportunities to address sex and gender and thereby strengthen research proposals.

Methods

Ontario investigators were invited to submit a draft of their health research proposal to the Sex and Gender Research Support Service (SGRSS) at Women’s College Hospital in Toronto, Ontario. The service works to build capacity on the integration of sex, gender, and other identity factors, in health research. Using the SAGER Guidelines and the METRICS for the Study of Sex and Gender in Human Participants as guides, proposals were reviewed to enhance their sex and gender considerations. Content analysis of the feedback provided these investigators was subsequently completed.

Results

Nearly 100 hundred study proposals were reviewed and investigators provided with suggestions on how to enhance their proposal. Analyzing the feedback provided across the reviewed studies revealed commonly overlooked opportunities to elevate consideration of sex and gender. These were organized into nine suggestions to mirror the sections of a research proposal.

Conclusion

Health researchers are often challenged on how to integrate a sex and gender lens into their work. Reviews completed across a range of health research studies show there are several commonly overlooked opportunities to do better in this regard. Nine ways to improve the integration of a sex and gender lens in health research proposals have been identified.
In vitro and in vivo anti-inflammatory activities of a sterol-enriched fraction from freshwater green alga, Spirogyra sp.
Authors: Wang Lei , Jeon You-Jin , Kim Jae-Il
Published: November 2020

Background

Inflammation plays a crucial role in the pathogenesis of many diseases such as arthritis and atherosclerosis. In the present study, we evaluated anti-inflammatory activity of sterol-rich fraction prepared from Spirogyra sp., a freshwater green alga, in an effort to find bioactive extracts derived from natural sources.

Methods

The sterol content of ethanol extract of Spirogyra sp. (SPE) was enriched by fractionation with hexane (SPEH), resulting 6.7 times higher than SPE. Using this fraction, the in vitro and in vivo anti-inflammatory activities were evaluated in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells and zebrafish.

Results

SPEH effectively and dose-dependently decreased the production of nitric oxide (NO) and prostaglandin E2 (PGE2). SPEH suppressed the production of pro-inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1β through downregulating nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW 264.7 cells without cytotoxicity. The in vivo test results indicated that SPEH significantly and dose-dependently reduced reactive oxygen species (ROS) generation, cell death, and NO production in LPS-stimulated zebrafish.

Conclusions

These results demonstrate that SPEH possesses strong in vitro and in vivo anti-inflammatory activities and has the potential to be used as healthcare or pharmaceutical material for the treatment of inflammatory diseases.
Validation of a menstrual pictogram and a daily bleeding diary for assessment of uterine fibroid treatment efficacy in clinical studies
Authors: Haberland Claudia , Filonenko Anna , Seitz Christian , Börner Matthias , Gerlinger Christoph , Doll Helen , Wessiepe Dorothea
Published: November 2020

Background

To evaluate the psychometric and measurement properties of two patient-reported outcome instruments, the menstrual pictogram superabsorbent polymer-containing version 3 (MP SAP-c v3) and Uterine Fibroid Daily Bleeding Diary (UF-DBD).

Test-retest reliability, criterion, construct validity, responsiveness, missingness and comparability of the MP SAP-c v3 and UF-DBD versus the alkaline hematin (AH) method and a patient global impression of severity (PGI-S) were analyzed in post hoc trial analyses.

Results

Analyses were based on data from up to 756 patients. The full range of MP SAP-c v3 and UF-DBD response options were used, with score distributions reflecting the cyclic character of the disease. Test-retest reliability of MP SAP-c v3 and UF-DBD scores was supported by acceptable intraclass correlation coefficients when stability was defined by the AH method and Patient Global Impression of Severity (PGI-S) scores (0.80–0.96 and 0.42–0.94, respectively). MP SAP-c v3 and UF-DBD scores demonstrated strong and moderate-to-strong correlations with menstrual blood loss assessed by the AH method. Scores increased in monotonic fashion, with greater disease severities, defined by the AH method and PGI-S scores; differences between groups were mostly statistically significant (P < 0.05). MP SAP-c v3 and UF-DBD were sensitive to changes in disease severity, defined by the AH method and PGI-S. MP SAP-c v3 and UF-DBD showed a lower frequency of missing patient data versus the AH method, and good agreement with the AH method.

Conclusions

This evidence supports the use of the MP SAP-c v3 and UF-DBD to assess clinical efficacy endpoints in UF phase III studies replacing the AH method.
Running a journal club in 2020: reflections and challenges
Authors: Mark Isabel , Sonbol Motaz , Abbasian Cyrus
Published: November 2020

The online environment brings both challenges and opportunities. The skills learned in journal clubs remain highly relevant where the ability to critique rapidly generated information and apply evidence to patient care is vital. Creativity and flexibility are needed to ensure that learners’ needs are met and efforts are made to involve those who may not be naturally drawn to online environments. This article explores how journal clubs have been approached in the past, both in person and more recently online, considers techniques for maintaining engagement in online teaching and proposes new approaches for future journal clubs.
Are we training psychiatrists to develop skills in intellectual disability psychiatry? Current European context and future directions
Authors: Casanova Dias Marisa , Perera Bhathika , Riese Florian , De Picker Livia , Pinto da Costa Mariana , Petricean Alina , Kanellopoulos Athanasios , Krysta Krzysztof , Baessler Franziska
Published: November 2020

The majority of people with intellectual disabilities (ID) and psychiatric disorders access mainstream mental health services across Europe. However, only 56% of countries provide postgraduate psychiatric training in ID according to a survey across 42 European countries. We explore the challenges of ID training and make recommendations for education and health policymakers.
Development and Implementation of an Oral Oncology Drug Repository Program
Authors: Stanz Lauren , Ulbrich Tim , Yucebay Filiz , Kennerly-Shah Julie
Published: November 2020

PURPOSE:

Because of high costs associated with oral oncology drugs, patients are often unable to afford their medications. Developing and implementing an oral oncology drug repository program can provide cost savings and waste reduction opportunities to oncology patients and health care systems.

METHODS:

Strategies to implement an oral oncology drug repository program include the following: (1) define patient eligibility requirements for the collected drug, (2) ensure patients have long-term availability to preferred treatment, (3) identify optimal oral oncology drugs to use, (4) provide safe drug collection with protocol, (5) calculate the amount of resources needed to provide services, (6) obtain adequate space to operate safely and efficiently, (7) establish safe disposal of the drug deemed inappropriate for use, and (8) spread awareness to prospective patient participants.

RESULTS:

To date, The Ohio State University Wexner Medical Center oral oncology drug repository program has received 11 drug collections and has redispensed drugs several times. With additional resources, the plan is to expand the repository program’s scope to include other drugs and reach more patients.

CONCLUSION:

Developing and implementing an oral oncology drug repository program for patients was logistically feasible due to strategic planning with many early successes. As national attention continues to be placed on reducing oral oncology drug costs, additional research is needed regarding strategies to best incorporate pharmacy services into innovative patient care opportunities.
Perioperative Renoprotection: Clinical Implications
Authors: Saadat-Gilani Khaschayar , Zarbock Alexander , Meersch Melanie
Published: November 2020

Acute kidney injury (AKI) remains a common complication in the perioperative setting affecting patients’ short- and long-term outcome. Because therapeutic options are restricted to the use of renal replacement therapy, preventive strategies have become increasingly important. Several substances have been investigated for preventing AKI with limited to no effects. The lacking effectiveness of all these therapies might be caused by the fact that the therapy was started too late. In all the studies, therapy was initiated once a reduced kidney function occurred. In contrast to the classical functional biomarkers, new renal biomarkers allow to identify kidney damage without a loss of function thus enabling the implementation of preventive measures at the stage of renal stress. The most promising preventive strategy to date seems to implement a bundle of supportive measures in patients at high risk for AKI as recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) group. This strategy includes the avoidance of nephrotoxic drugs and contrast agents, avoidance of hyperglycemia, optimization of perfusion pressure and hemodynamics with consideration of a functional hemodynamic monitoring, and close monitoring of renal function in patients at high risk for AKI. This review discusses new renal biomarkers for identifying kidney damage, the background of why the different measures of the KDIGO bundle might positively affect renal function and prevent the development of AKI, and presents the current literature of biomarker-based approaches in AKI.
Targeting Endothelial Dysfunction in Acute Critical Illness to Reduce Organ Failure
Authors: Juffermans Nicole P . , van den Brom Charissa E. , Kleinveld Derek J. B.
Published: November 2020

During hyperinflammatory conditions that can occur in acute critical illness, such as shock or hypoperfusion, inflammatory mediators activate the endothelium, fueling a proinflammatory host-response as well as procoagulant processes. These changes result in shedding of the glycocalyx, endothelial hyperpermeability, edema formation, and lead to disturbed microcirculatory perfusion and organ failure. Different fluid strategies that are used in shock may have differential effects on endothelial integrity. Collectively, low protein content fluids seem to have negative effects on the endothelial glycocalyx, aggravating endothelial hyperpermeability, whereas fluids containing albumin or plasma proteins may be superior to normal saline in protecting the glycocalyx and endothelial barrier function. Targeting the endothelium may be a therapeutic strategy to limit organ failure, which hitherto has not received much attention. Treatment targets aimed at restoring the endothelium should focus on maintaining glycocalyx function and/or targeting coagulation pathways or specific endothelial receptors. Potential treatments could be supplementing glycocalyx constituents or inhibiting glycocalyx breakdown. In this review, we summarize mechanisms of endothelial dysfunction during acute critical illness, such as the systemic inflammatory response, shedding of the glycocalyx, endothelial activation, and activation of coagulation. In addition, this review focuses on the effects of different fluid strategies on endothelial permeability. Also, potential mechanisms for treatment options to reduce endothelial hyperpermeability with ensuing organ failure are evaluated. Future research is needed to elucidate these pathways and to translate these data to the first human safety and feasibility trials.
Disease Mechanisms of Perioperative Organ Injury
Authors: Conrad Catharina , Eltzschig Holger K.
Published: November 2020

Despite substantial advances in anesthesia safety within the past decades, perioperative mortality remains a prevalent problem and can be considered among the top causes of death worldwide. Acute organ failure is a major risk factor of morbidity and mortality in surgical patients and develops primarily as a consequence of a dysregulated inflammatory response and insufficient tissue perfusion. Neurological dysfunction, myocardial ischemia, acute kidney injury, respiratory failure, intestinal dysfunction, and hepatic impairment are among the most serious complications impacting patient outcome and recovery. Pre-, intra-, and postoperative arrangements, such as enhanced recovery after surgery programs, can contribute to lowering the occurrence of organ dysfunction, and mortality rates have improved with the advent of specialized intensive care units and advances in procedures relating to extracorporeal organ support. However, no specific pharmacological therapies have proven effective in the prevention or reversal of perioperative organ injury. Therefore, understanding the underlying mechanisms of organ dysfunction is essential to identify novel treatment strategies to improve perioperative care and outcomes for surgical patients. This review focuses on recent knowledge of pathophysiological and molecular pathways leading to perioperative organ injury. Additionally, we highlight potential therapeutic targets relevant to the network of events that occur in clinical settings with organ failure.
Perioperative Lung Protection: General Mechanisms and Protective Approaches
Authors: Ball Lorenzo , Almondo Chiara , Pelosi Paolo
Published: November 2020

Postoperative pulmonary complications (PPCs) are one of the most important cause of perioperative morbidity and mortality in patients undergoing noncardiothoracic surgery, leading to increased hospital length of stay and mortality rate. The principal purpose of this review is to provide an overview of the perioperative lung protection strategies in patients undergoing elective noncardiothoracic surgery, informing clinicians on evidence-based perioperative care pathways. We also conducted a systematic review and meta-analysis of randomized controlled trials in noncardiothoracic surgery focusing on the following aspects: preoperative physiotherapy, intraoperative protective mechanical ventilation, postoperative prophylactic continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC), and postoperative physiotherapy. Both preoperative physiotherapy (relative risk [RR], 0.49, 95% confidence interval [CI], 0.35-0.69, P < .01) and postoperative CPAP (RR, 0.53, 95% CI, 0.30-0.94, P = .029) reduced the incidence of PPCs. Intraoperative protective mechanical ventilation had unclear effects (RR, 0.90, 95% CI, 0.77-1.06, P = .22). No benefits were observed for HFNC (RR, 0.88, 95% CI, 0.70-1.11, P = .30) and physiotherapy regimens administered in the postoperative period only (RR, 0.89, 95% CI, 0.69-1.16, P = .40). Lung-protective strategies should be considered throughout the entire perioperative period. The prophylactic use of strategies initiated in the postoperative period only, such as physiotherapy, CPAP, or HFNC, offers limited benefits. Physiotherapy and patient training should be started early in the preoperative phase, and intraoperative protective mechanical ventilation should be titrated on an individual basis taking into account all the available evidence.
Insertions of codons encoding basic amino acids in H7 hemagglutinins of influenza A viruses occur by recombination with RNA at hotspots near snoRNA binding sites
Authors: Gultyaev Alexander P. , Spronken Monique I. , Funk Mathis , Fouchier Ron A.M. , Richard Mathilde
Published: November 2020

The presence of multiple basic amino acids in the protease cleavage site of the hemagglutinin (HA) protein is the main molecular determinant of virulence of highly pathogenic avian influenza (HPAI) viruses. Recombination of HA RNA with other RNA molecules of host or virus origin is a dominant mechanism of multibasic cleavage site (MBCS) acquisition for H7 subtype HA. Using alignments of HA RNA sequences from documented cases of MBCS insertion due to recombination, we show that such recombination with host RNAs is most likely to occur at particular hotspots in ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), and viral RNAs. The locations of these hotspots in highly abundant RNAs indicate that RNA recombination is facilitated by the binding of small nucleolar RNA (snoRNA) near the recombination points.
Seroepidemiology of maternally-derived antibody against Group B Streptococcus (GBS) in Mulago/Kawempe Hospitals Uganda - PROGRESS GBS
Authors: Kyohere Mary , Davies Hannah Georgia , Musoke Philippa , Nakimuli Annettee , Tusubira Valerie , Tasimwa Hannington Baluku , Nsimire Juliet Sendagala , Heath Paul , Cose Stephen , Baker Carol , Le Doare Kirsty , Sekikubo Musa
Published: November 2020

Background: Group B Streptococcus (GBS) is a major contributor to the high burden of neonatal and young infant infectious disease in resource- limited settings. As disease protection during the first six months of life is provided via placental transfer of maternal antibodies, a maternal GBS vaccine may provide an effective strategy to reduce infectious death and disability. An efficacy study may be difficult because of the large sample size required and alternative approaches such as serocorrelates of protection based on natural antibody concentration are being considered. Such studies would need to be undertaken in high burden settings such as Uganda. We therefore aim to evaluate the feasibility and acceptability of a GBS sero-epidemiology study in Kampala, Uganda.

Methods: This is a prospective cohort and nested case-control study, conducted across two-centres with two entry points. A) consecutive women and their infants at birth, with collection of maternal swab, cord and maternal blood, and follow up by telephone until the infant is 3 months old; B) any infant under 3 months of age, presenting with signs of sepsis to any of the paediatric units, with collection of blood culture, cerebrospinal fluid and nasopharyngeal swabs. Any infants identified as having GBS disease (defined as GBS isolated from a normally sterile site) will be recruited and followed up for two years to assess their neurodevelopment. A nested qualitative study will investigate stakeholder (pregnant women and their families, healthcare workers and community leaders) opinions of sampling for such a study and understanding and potential uptake of vaccines in pregnancy.

Discussion: The primary aim is to determine anti-GBS antibody concentration in infants with GBS disease compared to healthy controls. Secondary outcomes include stillbirth and all-cause infection and acceptance of sample methods and vaccination. The findings will inform scalability and sustainability of the programme in Uganda.
Protocol for meta-research on the evidence informing micronutrient dietary reference intakes for pregnant and lactating women
Authors: He Siran , Klatt Kevin C. , Rahnavard Ali , Barberio Matthew D. , Gernand Alison D. , Smith Emily R.
Published: November 2020

Nutrient reference values are important parameters that guide nutrition and public health work globally. Micronutrient requirements during the peri-conception period are generally increased, which is essential in ensuring maternal, fetal, and neonatal health. Nevertheless, the current dietary reference intakes (DRIs) may be limited in terms of the methods used and the populations included, particularly the DRIs for pregnancy and lactation. In this proposed review, we will examine the methods (rigor of design, utilization of molecular methods, and presence of modern methods) and the population (inclusion of women, and in particular, pregnant and lactating people) in the studies used to inform the current DRIs. We will apply meta-science methods to this review, which involves formally reviewing the current evidence, and identifying opportunities to improve how we fund, perform, evaluate, and incorporate nutrition science into public health programs for better outcomes.
Epistles as a Medium of Late Ancient Literary Debates
Authors: Styka Jerzy
Published: November 2020

The aim of the paper is to show the fundamental role that the epistles played in late ancient literary life and intellectual exchange. The main source for this phenomenon are nine books of the letters of Sidonius Apollinaris (430-486), an important representative of 5th c. Gallic high culture, who was at the same time an important Roman politician and the Catholic church hierarch. In the present paper I am concentrating on the sources showing an image of Roman literary culture (still rich and strong at that time) in Northern and Central Gaul, the territories specially endangered by barbaric incursions. The state of affairs in these areas is less known, because the scholarly efforts concentrate on studying the refined intellectual and literary culture of Southern Gaul with its great city centers in Lyon, Narbonne, Bordeaux and Vienne. The examples presented here are, obviously, just a small selection of the great number of sources presented by Sidonius.
Civitas secum ipsa discors (II 23, 1)
Authors: Śnieżewski Stanisław
Published: November 2020

Livy tries to judge virtutes and vitia of both patricians and plebeians impartially. Naturally, Livy’s vision of the early republic presented in the first pentad is anachronic and discordant in reference to historical truth. In my opinion he supports an aristocratic republic and Augustus’s principate, but often criticizes patricians and highly estimates valours of the plebs. His observations on regnum, libertas, moderatio, discordia are noteworthy and rhetorically embellished. The language of political rhetoric is extended and close to invective. The struggle between the patricians and the plebeians is a poison (venenum) destroying the city. On the other hand, the best effects are brought out by concordia ordinum (e.g. II 1, 11). As in Vergil’s Aeneid very important are the martial, civil, religious, and familial virtues. The primal role, however, is played by virtus, understood for the most part as military courage (e.g. XXV 14, 1; IX 40, 6; XXIV 38, 2).