bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency of kdr mutations in the voltage-sensitive sodium channel (VSSC) gene in Aedes aegypti from Yogyakarta and implications for Wolbachia-infected mosquito trials
Authors: Wuliandari Juli Rochmijati , Hoffmann Ary A. , Tantowijoyo Warsito , Endersby-Harshman Nancy M.
Published: August 2020

Background

In the inner city of Yogyakarta, Indonesia, insecticide resistance is expected in the main dengue vector, Aedes aegypti, because of the intensive local application of pyrethroid insecticides. However, detailed information about the nature of resistance in this species is required to assist the release of Wolbachia mosquitoes in a dengue control program, so that we can ensure that insecticide resistance in the strain of Ae. aegypti being released matches that of the background population.

Methods

High-resolution melt genotyping was used to screen for kdr mutations associated with pyrethroid resistance in the voltage-sensitive sodium channel (VSSC) gene in Ae. aegypti of some areas in the inner city of Yogyakarta.

Results

The results show that the V1016G mutation predominated, with individuals homozygous for the 1016G allele at a frequency of 82.1% and the mutant allele G at a frequency of 92%. Two patterns of co-occurrence of mutations were detected in this study, homozygous individuals V1016G/S989P; and heterozygous individuals V1016G/F1534C/S989P. We found the simultaneous occurrence of kdr mutations V1016G and F1534C at all collection sites, but not within individual mosquitoes. Homozygous mutants at locus 1016 were homozygous wild-type at locus 1534 and vice versa, and heterozygous V1016G were also heterozygous for F1534C. The most common tri-locus genotype co-occurrences were homozygous mutant 1016GG and homozygous wild-type FF1534, combined with homozygous mutant 989PP (GG/FF/PP) at a frequency of 38.28%.

Conclusions

Given the relatively small differences in frequency of resistance alleles across the city area, locality variations in resistance should have minor implications for the success of Wolbachia mosquito trials being undertaken in the Yogyakarta area.
CAPICE: a computational method for Consequence-Agnostic Pathogenicity Interpretation of Clinical Exome variations
Authors: Li Shuang , van der Velde K. Joeri , de Ridder Dick , van Dijk Aalt D. J. , Soudis Dimitrios , Zwerwer Leslie R. , Deelen Patrick , Hendriksen Dennis , Charbon Bart , van Gijn Marielle E. , Abbott Kristin , Sikkema-Raddatz Birgit , van Diemen Cleo C. , Kerstjens-Frederikse Wilhelmina S. , Sinke Richard J. , Swertz Morris A.
Published: August 2020

Exome sequencing is now mainstream in clinical practice. However, identification of pathogenic Mendelian variants remains time-consuming, in part, because the limited accuracy of current computational prediction methods requires manual classification by experts. Here we introduce CAPICE, a new machine-learning-based method for prioritizing pathogenic variants, including SNVs and short InDels. CAPICE outperforms the best general (CADD, GAVIN) and consequence-type-specific (REVEL, ClinPred) computational prediction methods, for both rare and ultra-rare variants. CAPICE is easily added to diagnostic pipelines as pre-computed score file or command-line software, or using online MOLGENIS web service with API. Download CAPICE for free and open-source (LGPLv3) athttps://github.com/molgenis/capice.
Epigenome-wide DNA methylation profiling of preeclamptic placenta according to severe features
Authors: Lim Ji Hyae , Kang Yu-Jung , Bak Hye Jin , Kim Mi Sun , Lee Hyun Jung , Kwak Dong Wook , Han You Jung , Kim Moon Young , Boo Hyeyeon , Kim Shin Young , Ryu Hyun Mee
Published: August 2020

Background

Preeclampsia (PE) is an obstetric disorder with significant morbidities for both the mother and fetus possibly caused by a failure of the placental trophoblast invasion. However, its pathophysiology largely remains unclear. Here, we performed DNA methylation profiling to determine whether differential patterns of DNA methylation correlate with PE and severe features of PE.

Materials and methods

We extracted DNA from placental tissues of 13 normal, five PE, and eight PE pregnant women with severe features. Genome-wide DNA methylation analysis was performed using the Illumina HumanMethylation 850K BeadChip. New functional annotations of differentially methylated CpGs (DMCs) in PE were predicted using bioinformatics tools.

Results

Significant differences were evident for 398 DMCs, including 243 DMCs in PE and 155 DMCs in PE with severe features, compared with normal placental tissues. Of these, 12 hypermethylated DMCs and three hypomethylated DMCs were observed in both PE groups, thus were independent from severe features. Three hundred seventy-nine DMCs were identified by the presence or absence of severe features. Two hundred genes containing these DMCs were associated with developmental processes and cell morphogenesis. These genes were significantly associated with various PE complications such as disease susceptibility, viral infections, immune system diseases, endocrine disturbance, seizures, hematologic diseases, and thyroid diseases.

Conclusions

This is the first study to investigate the genome-scale DNA methylation profiles of PE placentas according to severe features. The epigenetic variation in the placentas probably resulted in altered developmental processes and immune dysregulation, contributing to PE. This study provides basic information to refine the clinical and pathological mechanisms of the severe features in placenta-mediated PE.
Adrenal insufficiency in coronavirus disease 2019: a case report
Authors: Heidarpour Maryam , Vakhshoori Mehrbod , Abbasi Saeed , Shafie Davood , Rezaei Nima
Published: August 2020

Background

Novel coronavirus disease 2019 presents with fever, dry cough, fatigue, and shortness of breath in most cases; however, some rare manifestations in other organs have also been reported so far.

Case presentation

Here, the case of a 69-year-old Iranian man with coronavirus disease 2019 is presented who suffered from frequent episodes of vasopressor-resistant hypotension during intensive care unit admission, which was finally attributed to the occurrence of acute adrenal insufficiency.

Conclusions

As this is a rare complication, adrenal insufficiency might be easily overlooked. However, early detection of this disease among critically ill patients infected with coronavirus disease 2019 could be lifesaving, especially among those unresponsive to vasopressor agents.
Effects of neurohormonal antagonists on blood pressure in patients with heart failure with reduced ejection fraction (HFrEF): a systematic review protocol
Authors: Guggilla Rama Krishna , Sowa Pawel Mateusz , Jamiolkowski Jacek , Sinnadurai Siamala , Amin Adnan , Kaminski Karol Adam
Published: August 2020

Background

Several cardiovascular pathologies cause heart failure. Heart failure with reduced ejection fraction (HFrEF) is deteriorated by neurohormonal activation, so neurohormonal antagonists are recommended in HFrEF patients. They improve morbidity, mortality, and quality of life and reduce hospital admissions. Heart failure treatment guidelines recommend achieving target doses of those drugs. However, many clinicians prescribe suboptimal doses for the fear of inducing hypotension. The aim of this systematic review and meta-analysis is to understand whether it is still beneficial to uptitrate the doses of those drugs even if the patient is at the risk of developing hypotension.

Methods

The primary outcome is symptomatic or asymptomatic hypotension in patients on neurohormonal antagonist drugs for HFrEF. Secondary outcomes are blood pressure reduction, New Yok Heart Association functional class deterioration, non-fatal cardiovascular events, cardiovascular mortality, all-cause mortality, heart failure hospitalizations, and adverse events. Randomized controlled trials involving adults with HFrEF will be included. Comprehensive literature search will be done in MEDLINE, Scopus, Web of Science, WHO Global Index Medicus, and the Cochrane Central Register of Controlled Trials. MEDLINE will be searched first using controlled vocabulary and free text terms and then adapted to other databases. Linear and nonlinear dose-response meta-analyses will be conducted. Publication bias and statistical heterogeneity will be tested by Egger’s regression and Cochran’s Q tests, respectively. Sensitivity, subgroup, and meta-regression analyses will be performed. Grading of Recommendations Assessment, Development and Evaluation approach will be used to judge the quality of evidence.

Discussion

This systematic review and meta-analysis will provide information about the risk of hypotension in patients on neurohormonal antagonist drugs for HFrEF. The results will be published in a peer-reviewed journal. The implications for further research will be discussed.

Systematic review registration

PROSPERO CRD42019140307
Developing an evidence-informed framework for safe and accessible urban mobility infrastructures for older adults in low- and middle-income countries: a protocol for realist synthesis
Authors: Patil Divya Sussana , Yadav Uday Narayan , George Sobin , Helbich Marco , Ettema Dick , Bailey Ajay
Published: August 2020

Background

Mobility, one of the basic daily activities, helps in carrying out routine work, which contributes to people’s well-being. A lack of friendly and accessible infrastructure may act as a barrier, which limits older adults’ contributions and participation in society. Hence, it is important to have an enabling environment for older adults to carry out their activities independently at ease. There is ample research evidence about effective interventions on urban mobility infrastructures, but there is a lack of evidence regarding what works, for whom, and in what circumstances. Hence, there is a need to identify the contextual factors for different regions to design region-specific interventions. The aim of this realist synthesis is to develop an evidence-informed framework for safe and accessible urban mobility infrastructures for older adults in low- and middle-income countries.

Methods

A realist review will be undertaken using the following process: (1) development of a program theory, (2) search strategy and information sources, (3) study selection and appraisal, (4) data extraction, and (5) data synthesis. In addition to searching grey literature and contacting authors, we will search (since inception) multiple electronic databases such as PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library. Studies will be included based on their ability to provide data that evaluates some aspect of the program theory. Two independent reviewers will screen and extract data from all relevant sources. A realist logic of analysis will be used to identify all context-mechanism-outcome that explains how safe and accessible urban mobility infrastructures for older adults implemented in low- and middle-income countries translate to better health outcomes. The findings will be reported according to Realist and MEta-narrative Evidence Syntheses: Evolving Standards guidelines.

Discussion

This realist review will help to develop a framework for safe and accessible urban mobility infrastructures for older adults in low- and middle-income countries. The results of this study will support evidence-based decision-making on urban mobility systems and will be of interest to various stakeholders. Dissemination will be done through conference presentations, policy briefs, media, and peer-reviewed journals. Implications for future research will be discussed.

Systematic review registration

PROSPERO CRD42020168020
Some new edge detecting techniques based on fractional derivatives with non-local and non-singular kernels
Authors: Ghanbari Behzad , Atangana Abdon
Published: August 2020

Computers and electronics play an enormous role in today’s society, impacting everything from communication and medicine to science. The development of computer-related technologies has led to the emergence of many new important interdisciplinary fields, including the field of image processing. Image processing tries to find new ways to access and extract information from digital images or videos. Due to this great importance, many researchers have tried to utilize new and powerful tools introduced in pure and applied mathematics to develop new concepts in imaging science. One of these valuable research areas is the contents of fractional differential calculus. In recent years, extensive applications to the new fractional operators have been employed in real-world problems. This article attempts to address a practical aspect of this era of research in the edge detecting of an image. For this purpose, two general structures are first proposed for making new fractional masks. Then the components in these two structures are evaluated using the fractional integral Atangana–Baleanu operator. The performance and effectiveness of these proposed designs are illustrated by several numerical simulations. A comparison of the results with the results of several well-known masks in the literature indicates that the results presented in this article are much more accurate and efficient. This is the main achievement of this article. These fractional masks are all novel and have been introduced for the first time in this contribution. Moreover, in terms of computational cost, the proposed fractional masks require almost the same amount of computations as the existing conventional ones. By observing the numerical simulations presented in the paper, it is easily understood that with proper adjustment for the fractional-order parameter, the accuracy of the obtained results can be significantly improved. Each of the new suggested structures in this article can be regarded as a valid and effective alternative for the well-known existing kernels in identifying the edges of an image.
An agribusiness perspective of demonetization in central region of the state of Gujarat in India
Authors: Singh Ritambhara , Prajapati Mahesh R.
Published: August 2020

This paper aims at understanding the effect of demonetization announced in November 2016 on agribusiness subsystems, its effect on consumer purchasing criteria, and the problems that surfaced in rural areas to move towards digitalization. This research was exploratory in nature and so adopted an open-ended approach through interviews of 200 farmers selected from 20 villages of two districts; one economically progressive and the other economically backward, in central region of the state of Gujarat in India. Besides, 50 landless farm laborers, 12 input dealers, 20 wholesalers, 20 retailers, 4 each of processors, exporters, and logistic service providers operating in study area were also interviewed. The focus group discussions were also conducted. Secondary data were gathered from various government sources. Exploratory factor analysis was conducted to examine the consumer purchasing criteria. Garrett’s ranking technique was used to find the problems of moving to digital transaction. The production activity slowed down due to immediate cash crunch. Agriculture also suffered a setback. Socio-economic factors contributed strongly to the consumer purchasing criteria post-demonetization. The rural economy worked on local credit basis during the demonetization period. Delayed sowing was observed due to non-availability of inputs during initial days of announcement of demonetization. Farm labor suffered losses. Prices of perishables crashed. More bank accounts opened in rural area as dairy payments were made mandatory through electronic mode only. Infrastructural bottlenecks, complex e-banking language and lack of technical knowhow, etc., posed problems before the rural economy to go digital. Strong policy interventions were suggested to make digitalization more popular in rural areas. Removal of infrastructural bottlenecks was suggested to absorb the shock effects of announcements like demonetization.
Useful parameters for the motion analysis of facial skin care in Japanese women
Authors: Sakai Shingo , Takatori Ruako , Nomura Mika , Uehara Kuniaki
Published: August 2020

Background

Facial skin care (FSC) is an important routine for Japanese women. Hand motions during FSC physically affect psychological state. However, it is very difficult to evaluate hand motions during personal and complex FSC. The objective of this study was to find out objective and quantitative parameters for hand motions during facial skin care (FSC). Women who enjoy and soothe during FSC (Enjoyment group (E group), n = 20) or not (non-enjoyment group (NE group), n = 19) were recruited by an advance questionnaire. The same lotion, emulsion, and cream were provided to all subjects, and they used sequentially in the same way as the women’s daily FSC. The motion of the marker on the back side of the right middle finger during FSC was tracked by a motion capture system. The heart rate variability (HRV) was also measured before and after FSC for evaluating psychological effect.

Results

The averaged acceleration (Avg. ACC), approximate entropy (ApEn), and power law scaling exponent (Rest γ) of the cumulative duration of slow motion from the sequential data of acceleration were evaluated. Compared to the NE group, the E group showed a lower Avg. ACC when using emulsion (p = 0.005) and cream (p = 0.007), a lower ApEn when using emulsion (p = 0.003), and a lower Rest γ (p = 0.024) when using all items, suggesting that compared to the NE group, the E group had more tender and regular motion, and sustainable slow motions, especially in the use of emulsion. In the E group, the low/high-frequency component of HRV decreased significantly after FSC, suggesting suppression of sympathetic activity (p = 0.045). NE group did not. For all subjects, ApEn and Rest γ showed significantly positive correlation with the increase in the low/high-frequency component of HRV after FSC (p < 0.01). ApEn showed significantly negative correlation with the increase in the high-frequency component of HRV after FSC (p < 0.05). Avg. ACC did not show significant correlation with them. These results suggested that the behavior of FSC influences the autonomic nerve system.

Conclusions

ApEn and Rest γ are useful parameters for evaluating quality of hand motions during FSC.
Exploring the impact of the COVID-19 pandemic and UK lockdown on individuals with experience of eating disorders
Authors: Branley-Bell Dawn , Talbot Catherine V.
Published: August 2020

Background

The coronavirus disease 2019 (COVID-19) pandemic may raise unique challenges for individuals with experience of eating disorders. Many factors have potential for detrimental impacts on psychological wellbeing and eating disorder recovery, including: Disruption to living situations, ‘social distancing’ restrictions, difficult access to healthcare, and societal changes to food behaviours and technology usage. To date, little is known on the impact of the pandemic on this population, particularly within the UK.

Method

A mixed-methods online survey was developed for the purpose of this study. Data was collected from 129 individuals currently experiencing, or in recovery from, an eating disorder during the early stages of the UK pandemic lockdown. Participants were aged between 16 and 65 years, with 121 participants identifying as female, 7 male and 1 participant preferring not to disclose their gender.

Results

Findings suggest that the pandemic is having a profound, negative impact upon individuals with experience of eating disorders. Eight key themes were generated: Disruption to living situation, increased social isolation and reduced access to usual support networks, changes to physical activity rates, reduced access to healthcare services, disruption to routine and perceived control, changes to relationship with food, increased exposure to triggering messages, and positive outcomes. The results suggest detrimental impacts on psychological wellbeing including decreased feelings of control, increased feelings of social isolation, increased rumination about disordered eating, and low feelings of social support.

Conclusions

Individuals with eating disorders are at significant risk of negative impacts of the pandemic. There is a vital need for interventions to support this population. Inequalities in healthcare provision were identified, emphasising a need for a more cohesive approach to remote treatment across UK healthcare services. Positive aspects of technology use were identified but the results suggest a need to address and/or limit the potential for negative impacts of public messages around food and exercise behaviours, and to co-design technologies with end-users to facilitate effective treatment.
Just data? Solidarity and justice in data-driven medicine
Authors: Hummel Patrik , Braun Matthias
Published: August 2020

This paper argues that data-driven medicine gives rise to a particular normative challenge. Against the backdrop of a distinction between the good and the right, harnessing personal health data towards the development and refinement of data-driven medicine is to be welcomed from the perspective of the good. Enacting solidarity drives progress in research and clinical practice. At the same time, such acts of sharing could—especially considering current developments in big data and artificial intelligence—compromise the right by leading to injustices and affecting concrete modes of individual self-determination. In order to address this potential tension, two key elements for ethical reflection on data-driven medicine are proposed: the controllability of information flows, including technical infrastructures that are conducive towards controllability, and a paradigm shift towards output-orientation in governance and policy.
Percutaneous transesophageal gastro-tubing for the management of anastomotic leakage after upper GI surgery: a report of two clinical cases
Authors: Tamamori Yutaka , Sakurai Katsunobu , Kubo Naoshi , Yonemitsu Ken , Fukui Yasuhiro , Nishimura Junya , Maeda Kiyoshi , Nishiguchi Yukio
Published: August 2020

Background

Anastomotic leakage is a serious, sometimes critical complication of upper gastrointestinal (GI) surgery. The cavity and target drainage tubes are difficult to reach; therefore, a nasogastric tube (NGT) and fasting are required for an extended period. We successfully treated and managed two patients with anastomotic leakage using percutaneous transesophageal gastro-tubing (PTEG).

Case presentation

In case 1, a 79-year-old man with gastric cancer underwent total gastrectomy; 1 week later, he underwent emergent open laparotomy due to panperitonitis attributed to anastomotic leakage-related jejunojejunostomy. We resected the portion between esophagojejunostomy and jejunojejunostomy and reconstructed it using the Roux-en-Y technique. On postoperative day (POD) 9, anastomotic leakage was diagnosed at the esophagojejunostomy site and jejunotomy staple line. After using a circular stapler for jejunojejunostomy, a stapled jejunal closure was added. We inserted an NGT and performed aspiration for bowel decompression. As he did not improve within 2 weeks, we decided to perform PTEG to free him of the NGT. We kept performing intermittent aspiration; leakage stopped shortly after, due to effective inner drainage. The PTEG catheter was removed after oral intake was restarted. In case 2, an 81-year-old man with esophagogastric junction cancer underwent resection of the distal esophagus and proximal stomach. After shaping the remnant stomach, esophagogastrostomy was performed under the right thoracotomy. On POD 11, anastomotic leakage was identified, along with a mediastinal abscess. We inserted an NGT into the abscess cavity through the anastomotic leakage site. On POD 25, we performed PTEG and inserted a drainage tube, instead of an NGT. Although the abscess cavity disappeared, anastomotic leakage persisted as a fistula. We exchanged the PTEG with a double elementary diet (W-ED) tube with jejunal extension, with the side hole located near the anastomosis. The anastomotic fistula disappeared after treatment. Dysphagia persisted due to disuse atrophy of swallowing musculature; PTEG was useful for enteral feeding, even after the leakage occurred.

Conclusion

Patients are sometimes forced to endure pain for a long time for transnasal inner drainage. Using PTEG, patients will be free of sinus pain and discomfort; PTEG should be helpful for patients withstanding NGT.
S1-induced vasospastic angina—diagnostic utility of Holter ECG: a report of a case
Authors: Kanda Tatsuo , Wakai Atsuhiro , Chida Tadasu , Nakamura Yuichi
Published: August 2020

Background

Vasospastic angina is a rare but potentially life-threatening adverse event (AE) of S1, an oral fluoropyrimidine anticancer agent. However, this AE is not well known owing to its low incidence. We report herein a case of a patient who suffered from vasospastic angina associated with S1 chemotherapy for unresectable gastric adenocarcinoma, along with a review of the literature.

Case presentation

A 68-year-old woman was endoscopically diagnosed with gastric adenocarcinoma of the diffuse type. Abdominal pelvic contrast-enhanced computed tomography (CT) revealed small nodules in the omentum and ascites in the pouch of Douglas. The patient was clinically diagnosed with unresectable gastric adenocarcinoma with peritoneal metastasis, and primary chemotherapy with S1 plus cisplatin was selected. Around midnight of day 1, the patient complained of sudden oppressive chest pain. The pain disappeared spontaneously after 3–5 min, but similar events happened every midnight thereafter. No significant change was found on bedside electrocardiograms (ECGs) recorded immediately after the pain attacks. The patient was suspected to have unstable angina and underwent Holter ECG on day 4 of treatment. Holter ECG revealed ST segment elevations and short-run ventricular tachycardia during a pain attack. S1 chemotherapy was discontinued, and no attack was observed thereafter. Coronary CT angiography showed no significant stenosis of coronary arteries.

Conclusions

Clinicians should be aware of vasospastic angina as a serious AE in the chemotherapy with S1. Holter ECG is useful for the early diagnosis of this rare and clinically important AE.
Parent-child communication about sex and romantic feelings: does having older siblings make a difference?
Authors: Pasqualini Marta , De Rose Alessandra
Published: August 2020

Parental involvement in sex education and the quality of parent-child communication about romantic feelings appear to have a protective effect on adolescent sexual behaviours. However, little research has been conducted on the role played by birth order in the level of parental involvement in sex education. This is the first study seeking to address if the quality of parent-child communication about sex and romantic sentiments differs according to whether respondents have—or do not have—older siblings in Italy. Hypotheses concerning the role of sib-ship gender composition have been tested in order to explain potential intervening mechanisms. Data were drawn from the Sexual and Emotional Life of Youths survey (SELFY), a cross-sectional survey conducted in 2000 and in 2017 on Italian university students (N = 12,265). Our findings identify later-born children as the least likely to confide in parents. Although boys are generally less likely to talk to parents than girls, respondent gender does not moderate the effect of birth order. Instead, sib-ship gender composition plays a role: having grown up with at least one same-gender sibling is associated with a lower communication with parents about intimate matters. This study suggests that growing up with siblings, namely with same-gender siblings, make a difference in parent-child communication and this should be considered while evaluating the role of parental involvement in adolescent sexual education.
What is an estimand & how does it relate to quantifying the effect of treatment on patient-reported quality of life outcomes in clinical trials?
Authors: Lawrance Rachael , Degtyarev Evgeny , Griffiths Philip , Trask Peter , Lau Helen , D’Alessio Denise , Griebsch Ingolf , Wallenstein Gudrun , Cocks Kim , Rufibach Kaspar
Published: August 2020

Background

Published in 2019, a new addendum to the ICH E9 guideline presents the estimand framework as a systematic approach to ensure alignment among clinical trial objectives, trial execution/conduct, statistical analyses, and interpretation of results. The use of the estimand framework for describing clinical trial objectives has yet to be extensively considered in the context of patient-reported outcomes (PROs). We discuss the application of the estimand framework to PRO objectives when designing clinical trials in the future, with a focus on PRO outcomes in oncology trial settings as our example.

Main

We describe the components of an estimand and take a naïve PRO trial objective to illustrate how to apply attributes described in the estimand framework to inform construction of a detailed clinical trial objective and its related estimand. We discuss identifying potential post-randomization events that alter the interpretation of the endpoint or render its observation impossible (also defined as intercurrent events) in the context of PRO endpoints, and the implications of how to handle intercurrent events in the construction of the PRO objective. Using a simple objective statement,“What is the effect of treatment X on patient’s quality of life?”,we build up an example estimand statement and also use a previously published phase III oncology clinical trial to illustrate how an estimand for a PRO objective could have been written to align to the estimate framework.

Conclusion

The use of the estimand framework, as described in the new ICH E9 (R1) addendum guideline will become a key common framework for developing clinical trial objectives for evaluating effects of treatment. In the context of considering PROs, the framework provides an opportunity to more precisely specify and build the rationale for patient-focused objectives. This will help to ensure that clinical trials used for registration are designed and analysed appropriately, enabling all stakeholders to accurately interpret conclusions about the treatment effects for patient-focused outcomes.
Active human herpesvirus infections in adults with systemic lupus erythematosus and correlation with the SLEDAI score
Authors: Reis Alex Domingos , Mudinutti Cristiane , de Freitas Peigo Murilo , Leon Lucas Lopes , Costallat Lilian Tereza Lavras , Rossi Claudio Lucio , Costa Sandra Cecília Botelho , Bonon Sandra Helena Alves
Published: August 2020

Background

Human herpesviruses (HHVs) are responsible for a significant number of clinical manifestations in systemic lupus erythematous (SLE) patients. The aim of this study was to determine the frequency of active HHV infections in SLE patients and correlating them with disease activity.

Methods

Serum samples were collected from 71 SLE patients and their DNAs were extracted and analyzed to detect HHV-DNA viruses using the nucleic acid amplification technique.

Results

Fifteen out of the 71 (21.1%) patients tested positive for the HHV-DNA virus. Of them, 11/15 HHV-DNA-positive patients (73.3%) had SLE activity index (SLEDAI – Systemic Lupus Erythematosus Disease Activity Index) ≥8 (p = 0.0001). Active HCMV infection was the mostly frequently observed infection, occurring in 6/15 patients (40%). The frequencies of other active viral infections were 22% for HSV-1, 16.7% for HHV-7, and 5.5% for HSV-2. Viral coinfection (two or more viruses detected in the same sample) occurred in three patients (16.7%). Active HHV infections in SLE patients are more frequent in those with active SLE (≥8), who is at high risk of HHV reactivation and HCMV disease.

Conclusion

Viral surveillance is important to identify active HHV infections that can cause clinical symptoms and other complication in SLE patients.
Viral hepatitis and interstitial lung diseases: can HRCT assess their relation and characterize its pattern?
Authors: Samir Ahmed , El-Beheiry Ahmed Adel , Gharraf Heba Said , Khalifa Mohamed Hossameldin
Published: August 2020

Background

Clinical and pathological studies suggested the presence of a relation between active viral hepatitis and interstitial lung diseases (ILD) ranging from mild to moderate relation. Most studies attribute this relation to viral geno-physiological characteristics. The purpose of the study is first to assess the role of high-resolution computed tomography (HRCT) in evaluating the relation between viral hepatitis and ILDs, then to characterize the predominant pattern of ILD that affects patient management and prognosis.

Results

This prospective study was conducted on 300 patients with viral hepatitis. They were divided into three groups of patients according to blood viremia assessed by polymerase chain reaction (PCR) as well as the diffusing capacity of carbon monoxide (DlCO) in examined pulmonary function tests (PFT).Group [A]included 100 patients with low or moderate viremia and showing normal or low to moderate DlCOdecline (> 50%).Group [B]included 100 patients with high viremia and showing normal or low to moderate DlCOdecline (> 50%).Group [C]included 100 patients with high viremia and showing a restrictive DlCOdecline pattern (< 50%). The study included 182 males and 118 females with a ratio of 3:2, while the age ranged between 40 and 70 years (mean age of 55 years).No ILDwas found among the group [A] patient. Meanwhile, 27% of patients in the group [B] showeda non-fibrotic pattern of ILDand 50% of patients in the group [C] showeda fibrotic pattern of ILD. Among patients in group [B] and group [C] together, 77 patients showed ILD accounting for 38.5%.

Conclusion

In concordance with the results of the previous clinicopathological and geno-physiological studies, our HRCT results further established a mild to moderate relation between active hepatitis and ILD regardless of the pulmonary functions. The fibrotic pattern of ILD with poor response to therapy and poor prognosis was found in those patients with concomitant restrictive PFT and rapidly progressive symptoms.
Antioxidant activities of some edaphic algae in Egypt
Authors: El-Tablawy Neamat H. , Mansour Hoda A. , Shaaban Abd El-Salam M.
Published: August 2020

Background

Algae in general characterized by their rich content of biological compounds. However, few studies were conducted on the soil-inhabiting algae and their antioxidant characteristics.

Results

The present study was designed to evaluate the antioxidant activity of four edaphic algae including one on-soil alga (Vaucheria geminata) and three axenic isolated in-soil algae (Pleurochloris pyrenoidosa,Botrydiopsis eriensis, andScenedesmus obliquus). Total antioxidant activity by Phosphomolybdenum assay ranged from 6.66 to 36.33 mg of Asc/g dwt; meanwhile, the percentage inhibition of DPPH radical was up to 97.37%. Antioxidant activity of each alga was assessed also by measuring their contents of total phenols, flavonoids, and pigments (chlorophyllaand carotenoids).B. eriensisandS. obliquusrecorded the highest levels of phenols, flavonoids, and chlorophyllafollowed byP. pyrenoidosaandV. geminata, whileB. eriensisshowed the highest carotenoids content. Moreover, about seven types of each phenol and flavonoid compound were identified by HPLC chromatography in the four algae under investigation. The most common detected phenols were gallic, chlorogenic, caffeic, and ferulic, while rutin, quercetin, apigenin, and quercitrin were the most abundant flavonoids among all algae under investigation.

Conclusion

All the tested algae were characterized with high antioxidant activities besides the rich contents of compounds with antioxidant properties which recommend their further potential using in nutritional, pharmaceutical, and medicinal implications.
Prevalence and characteristics of neuropsychiatric involvement in an Egyptian cohort of systemic lupus erythematosus patients: a single-center retrospective cohort
Authors: M Medhat Basma , Moghazy Abdelkawy , Eissa Mervat
Published: August 2020

Background

The aim of this study was to retrospectively investigate the prevalence and characteristics of neuropsychiatric (NP) involvement in a cohort of systemic lupus erythematosus (SLE) patients from a single tertiary center.

Results

Of 301 included patients’ medical records, the prevalence of NPSLE, that was defined according to the American College of Rheumatology Nomenclature of 1999, was 33.5% (101/301), of whom 10 (9.9%) were males. The mean age at the last visit of patients with NP involvement was 29.1 ± 8.2 years, whereas the mean age at onset was 21.9 ± 7.3 years, and the mean disease duration was 89.8 ± 59.4 months. The most common NP manifestations were psychosis [34/101 (33.7%)], followed by seizures [22/101 (21.8%)]. Compared to those without NPSLE, patients with NP involvement were characterized by having a younger age of onset (p < 0.001) had a longer disease duration (p = 0.02). Of the cumulative characteristics recorded, NPSLE patients showed a higher prevalence of cutaneous vasculitis (p = 0.002), discoid rash (p = 0.03), pleurisy and pleural effusion (p = 0.004, p = 0.03, respectively), pericarditis (p = 0.007), thrombocytopenia (p = 0.04), and secondary antiphospholipid (APS) (p = 0.04); however, there was no difference in any of the included serologic features between the two groups. Patients with NPSLE had a higher median disease activity score [Systemic Lupus Erythematosus Disease Activity Index-2 K (SLEDAI-2 K)] at the disease onset (p = 0.008), yet it was comparable to those without NP involvement at the last visit (p = 0.3). NPSLE patients demonstrated a higher median damage score (p < 0.001) that was assessed according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score. NPSLE patients with secondary APS showed a higher prevalence of cerebrovascular accidents (CVA) (p < 0.001), while those without APS developed psychosis more frequently (p = 0.03).

Conclusion

Neuropsychiatric SLE patients (33.5%) demonstrated a younger age of onset, higher prevalence of secondary APS and distinct clinical characteristics, and had higher disease damage. APS-positive NPSLE patients had a higher prevalence of CVA, while APS-negative patients showed a higher prevalence of psychosis.
Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): Results of a randomized phase II trial
Authors: O'Shaughnessy J. , Osborne C. , Pippen J. , Yoffe M. , Patt D. , Monaghan G. , Rocha C. , Ossovskaya V. , Sherman B. , Bradley C.
Published: August 2020

3

The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology.

[Table: see text]
Risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors
Authors: Aubert R. E. , Stanek E. J. , Yao J. , Teagarden J. R. , Subar M. , Epstein R. S. , Skaar T. C. , Desta Z. , Flockhart D. A.
Published: August 2020

CRA508

The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology.

[Table: see text]
Concomitant CYP2D6 inhibitor use and tamoxifen adherence in early-stage breast cancer: A pharmacoepidemiological study
Authors: Dezentje V. , Van Blijderveen N. J. , Gelderblom H. , Putter H. , Van Herk-Sukel M. P. , Casparie M. K. , Egberts A. C. , Nortier J. W. , Guchelaar H. J.
Published: August 2020

CRA509

The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology.

No significant financial relationships to disclose.
Long-term follow-up and factors of survival of HER-2 positive breast cancer patients treated either by neoadjuvant trastuzumab docetaxel (TAXHER-S01 study) or by neoadjuvant trastuzumab docetaxel carboplatin (GETN[A]1 study)
Authors: Favier L. , Liegard M. , Guiu S. , van Praagh I. , Largillier R. , Weber B. , Coeffic D. , Vasseur B. , Coudert B.
Published: August 2020

e11507

Background: Almost 20% of breast cancers over express Her2, which is associated with a more aggressive phenotype and with a decreased survival. Nevertheless, trastuzumab (T) has been a revolutionary step in the adjuvant and in the metastatic treatments of Her2 positive breast cancers. Here, we focus on neoadjuvant T and try to determine the factors correlating with disease free survival and with overall survival in Her2 positive breast cancer treated with T based neoadjuvant chemotherapy. Methods: Data from two published T based neoadjuvant phases II were used: the TAX-HER trial which studied the use of 6 courses of 3 weekly docetaxel with weekly neoadjuvant T (scheme TH) (Coudert et. al. Annals of Oncology 2006) and the GET(N)A-1 trial which studied the use of 6 courses of 3 weekly docetaxel and carboplatin along with weekly neoadjuvant T (scheme TCH) followed by 3 weekly adjuvant T (Coudert et. al. JCO 2007). Moreover, additional patients from our institution and treated by neoadjuvant TH and adjuvant T were included. Survival curves were estimated using Kaplan-Meier methods and compared by log-rank test. Results: Data was available for 128 patients. 62 patients (48.4%) received neoadjuvant TH from whom 39 did not receive adjuvant T. 66 (51.6%) received neoadjuvant TCH and adjuvant T. Tumors characteristics were as followed: 65 (50.7%) SBR 1–2, 54 (42.19%) SBR 3, 49 (38.28%) hormonal receptors (RH) negative and 72 (56.25%) RH positive. The rate of pathological complete response (pCR) (Chevalier 1/2) was 39.6%. Overall survival (OS) for the entire cohort was 74,8 months. Relapse was defined as local, regional, metastatic relapse or death. Survival without relapse (SR) was 74.8 months. No difference was noted in OS and in SR according to the type of chemotherapy, TH or TCH. pCR did significantly influence SR (p = 0. 03) and survival without local recurrence (SLR) (p = 0.04) but neither OS nor survival without metastatic relapse (SMR). Multivariate analysis demonstrated that OS was correlated with node response (as defined by sataloff grade NA or NB) (p=0.0275) and the use of hormonal therapy in RH positive tumors (p=0.0724).

[Table: see text]
Predictors of invasive breast cancer or DCIS recurrence in estrogen receptor positive (ER+) and estrogen receptor negative (ER-) ductal carcinoma in situ (DCIS) patients with and without associated invasive carcinoma (IC)
Authors: Picarsic J. , Brufsky A. , Onisko A. , Chivukula M.
Published: August 2020

e11523

Background: DCIS is a heterogeneous pre-invasive carcinoma with a spectrum of clinical behavior. Patients with ER+ IC have better outcomes compared to ER- patients. FOXA1 and GATA 3 family of transcription factors have been shown to be associated with hormone receptors (ER and PR) and other variables of good prognosis with better overall and relapse-free survival rate. The specific aim of this study is to analyze the expression of these novel biological markers: FOXA1, GATA-3, with recognized markers: MIB-1(Ki-67) and HER2 /neu in DCIS patients with/without associated IC. Methods: Sixty-nine (69) cases of DCIS [(fifty two (52) cases in ER+; seventeen (17) in ER-] were retrieved from our Pathology database. The expressions of the biological markers are analyzed by using a panel of immunohistochemical stains. FOXA1, GATA 3, ER, PR are nuclear stains, a cumulative “H score” is derived based on proportionality (PS) and intensity scores (IS). A proliferation index (PI) is calculated for MIB-1 (Ki67) nuclear stain (low <10%, moderate 11–25%, high 26–50%, very high>50%). Her2/neu is scored as per guidelines for HercepTest (0, or 1+ =negative, 2+ =weakly positive, 3+ =strongly positive). Results: DCIS is categorized into low grade (LG) (nuclear grade 1 and 2), high grade (HG) (grade 3). In the HGDCIS (n=48), four (4) cases had IC after a mean of 7.75 years; three cases of recurrent DCIS after a mean 6 years. No recurrent IC or DCIS is seen in the LGDCIS (n=21) group. The results are shown in the Table . Conclusions: (1) Decreased expression of GATA 3 is observed in HGDCIS ER- group may be a contributor to higher recurrence observed in this group (14%) versus (0%) in ER+ group. (2) A strong expression of FOXA, GATA3, low Ki-67 index, absent Her 2 expression are characteristically seen in our ER+ DCIS group, as previously described in IC. 3. Comparing the response to therapy and outcome in the ER+ and ER- groups is on going.

[Table: see text]

No significant financial relationships to disclose.
The role of preoperative neoadjuvant cytoreductive dose-dense bevacizumab plus docetaxel followed by bevacizumab-doxorubicin-cyclophosphamide regimen in locally advanced operable breast cancer
Authors: Waintraub S. E. , Tuchman V.
Published: August 2020

e11524

Background: Neoadjuvant Rx has been shown to downstage locally advanced breast cancer (LABC) to try to achieve a pathological complete response(PCR) and to convert mastectomy to lumpectomy. Bevacizumab (B) was recently approved to treat metastatic breast cancer in combination with paclitaxel (P). NSABP B-27 used preoperative doxorubicin(A) with cyclophosphamide (C) +- docetaxel (Doc) every 3 wks in primary operable breast cancer, yielding a 12.9% PCR with no residual invasive cancer from AC and 26.1% with the addition of Doc. Based on the success of E2100 with P+B over P, and the more recent AVADO trial showing the superiority of B and Doc over Doc, we have treated such Her2neu-neg pts using Doc/B followed by AC/B with a dose dense every (q) 2 week regimen to see if we could achieve a higher PCR rate and to assess the tolerability of this regimen. Methods: Pts with Her2neu-negative locally advanced operable M0 breast cancer were treated initially with B 10mg/kg iv q 2w with Doc 100mg/m2 q 2w four times with pegfilgrastim given 24 hours after chemotherapy, followed by A 60mg/m2 and C 600mg/m2 q 2 weeks four 4 times with pegfilgrastim given 24 hours after chemotherapy with B 10mg/kg iv for the first AC course as the B was discontinued at least 6 weeks prior to definitive breast surgery. All pts were to get radiation therapy after surgery and appropriate anti-estrogen Rx if estrogen receptor was positive. Results: 15 Her-2 neg women aged 35–61 were treated from 9/06-present for locally advanced primary operable breast cancer. All pts had clinically significant tumor reduction. Of the first 12 post-operative evaluable pts that have completed all the pre- operative therapy, the results showed 5 PCR, including one pt with residual sub-cm DCIS, 7 pathological incomplete responses, yielding a 42% PCR. 3 of the 5 PCR pts had lumpectomies. The major toxicity was excessive eye tearing, nail bed changes and lethargy. Conclusions: This novel dose dense q 2 week regimen is safe, tolerable and effective in LABC with acceptable toxicity. The addition of B to dose dense traditional neoadjuvant chemotherapy seems to increase the PCR. Larger prospective trials using B with dose dense therapy are warranted.

No significant financial relationships to disclose.