bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Meal Absorption Model for Artificial Pancreas Systems
Authors: Diamond Travis , Cameron Faye , Bequette B. Wayne
Published: March 2021

Background:

Artificial pancreas (AP) systems reduce the treatment burden of Type 1 Diabetes by automatically regulating blood glucose (BG) levels. While many disturbances stand in the way of fully closed-loop (automated) control, unannounced meals remain the greatest challenge. Furthermore, different types of meals can have significantly different glucose responses, further increasing the uncertainty surrounding the meal.

Methods:

Effective attenuation of a meal requires quick and accurate insulin delivery because of slow insulin action relative to meal effects on BG. The proposed Variable Hump (VH) model adapts to meals of varying compositions by inferring both meal size and shape. To appropriately address the uncertainty of meal size, the model divides meal absorption into two disjoint regions: a region with coarse meal size predictions followed by a fine-grain region where predictions are fine-tuned by adapting to the meal shape.

Results:

Using gold-standard triple tracer meal data, the proposed VH model is compared to three simpler second-order response models. The proposed VH model increased model fit capacity by 22% and prediction accuracy by 12% relative to the next best models. A 47% increase in the accuracy of uncertainty predictions was also found. In a simple control scenario, the controller governed by the proposed VH model provided insulin just as fast or faster than the controller governed by the other models in four out of the six meals. While the controllers governed by the other models all delivered at least a 25% excess of insulin at their worst, the VH model controller only delivered 9% excess at its worst.

Conclusions:

The VH Model performed best in accuracy metrics and succeeded over the other models in providing insulin quickly and accurately in a simple implementation. Use in an AP system may improve prediction accuracy and lead to better control around mealtimes.
Anthropocene islands: There are only islands after the end of the world
Authors: Chandler David , Pugh Jonathan
Published: March 2021

Many Anthropocene scholars provide us with the key take home message that they are writing ‘after the end of the world’. Not because they are writing about apocalypse, but because they are engaging the Anthropocene after the profound crisis of faith in Western modernity which has swept across academia in recent decades. Here the dominant problematic of contemporary Anthropocene thinking has rapidly turned away from modernity’s human/nature divide to that of ‘relational entanglements’. Thus, Anthropocene scholarship is taking a particular interest in geographical forms and cultures which are held to bring this problematic to the fore for more intensive interrogation. In this article, we examine how the figure of the island as a liminal and transgressive space has facilitated Anthropocene thinking, working with and upon island forms and imaginations to develop alternatives to hegemonic, modern, ‘mainland’, or ‘one world’ thinking. Thus, whilst islands, under modern frameworks of reasoning, were reductively understood as isolated, backward, dependent, vulnerable, and in need of saving by others, the island is being productively re-thought in and for more recent Anthropocene thinking. We explain how islands have shifted from the margins in a number of international debates, becoming key sites for understanding relational entanglements, enabling alternative forms of thought and practice in the Anthropocene.
Corporate Social Responsibility Measures: A Brief Review
Authors: Shukla Akanksha , Geetika  , Shukla Nimesh
Published: March 2021

Studies are being conducted to measure the impact of corporate social responsibility (CSR) on different dimensions of performance of the firm. Therefore, it becomes imperative to measure CSR activities undertaken by the firms. The measures used to assess CSR range from quantitative to perceptual; hence, the study proposes to present an analytical profile of various methods used to measure CSR. The article reviews studies that span over the time period from the 1980s to 2016 to determine the relationship between CSR and performance of the firm. Various measures of CSR used in studies are broadly categorized as rating-based measures, financial measures, perceptual measures, and disclosure-based measures.

The study revealed that perceptual and rating-based measures are the most commonly used measures. Also, it has been found that the operationalization of CSR using these two measures has been used in the studies that are conducted mainly in developed countries. However, disclosure of CSR and expenditure made on social responsibility can be more comprehensive measures as they are more objective in nature and are not influenced by the biases. Also, expenditure on CSR can be a useful measure while conducting a cost-benefit analysis of CSR activities performed by the organizations.
A comparative study of children’s Chinese character textbooks in Korea and China, with a focus on Yu Hap
Authors: Yeon Sil Jeong , Eun Young Jang , Heung Soo Park
Published: March 2021

This study examines why and how Chinese characters spread into Korea. It subsequently conducts a comparative analysis of Korean and Chinese children’s textbooks with a focus on Yu Hap from the perspective of the acceptance and acculturation of Chinese characters. It also explores how commonly used the characters in Yu Hap are, and the text’s learning value as one of Korea’s children’s textbooks. Yu Hap is very significant as the first written language textbook published in Korea. A comparative analysis of the characters used in four children’s books published in Korea found that the characters in Yu Hap are very common, and the text has a high learning value. Approximately 50% of the characters in San Bai Qian and Yu Hap are the same, showing that both China and Korea had similar perceptions of the characters in common use. A very significant proportion of characters overlap in Basic Chinese Character for Educational Use, List of Common Words in Modern Chinese, and Yu Hap; this supports the idea that the same characters have continued to be used from ancient times to the present day.
Precision medicine in acute respiratory distress syndrome: workshop report and recommendations for future research
Authors: Bos Lieuwe D.J. , Artigas Antonio , Constantin Jean-Michel , Hagens Laura A. , Heijnen Nanon , Laffey John G. , Meyer Nuala , Papazian Laurent , Pisani Lara , Schultz Marcus J. , Shankar-Hari Manu , Smit Marry R. , Summers Charlotte , Ware Lorraine B. , Scala Raffaele , Calfee Carolyn S.
Published: March 2021

Acute respiratory distress syndrome (ARDS) is a devastating critical illness that can be triggered by a wide range of insults and remains associated with a high mortality of around 40%. The search for targeted treatment for ARDS has been disappointing, possibly due to the enormous heterogeneity within the syndrome. In this perspective from the European Respiratory Society research seminar on “Precision medicine in ARDS”, we will summarise the current evidence for heterogeneity, explore the evidence in favour of precision medicine and provide a roadmap for further research in ARDS. There is evident variation in the presentation of ARDS on three distinct levels: 1) aetiological; 2) physiological and 3) biological, which leads us to the conclusion that there is no typical ARDS. The lack of a common presentation implies that intervention studies in patients with ARDS need to be phenotype aware and apply a precision medicine approach in order to avoid the lack of success in therapeutic trials that we faced in recent decades. Deeper phenotyping and integrative analysis of the sources of variation might result in identification of additional treatable traits that represent specific pathobiological mechanisms, or so-called endotypes.
Percutaneous spinal endoscopy with unilateral interlaminar approach to perform bilateral decompression for central lumbar spinal stenosis: radiographic and clinical assessment
Authors: Xue Jingbo , Chen Haoxiang , Zhu Bin , Li Xuelin , Ouyang Zhihua , Li Shan , Xu Zhun , Xie Yong , Yan Yiguo
Published: March 2021

Background

Recently, a percutaneous spinal endoscopy unilateral posterior interlaminar approach to perform bilateral decompression has been proposed for use in treatment of lumbar spinal stenosis, As a development and supplement to traditional surgery, its advantages regarding therapeutic effects and prognosis, such as minor soft tissue damage, little intraoperative blood loss, and a quick return to daily life. However, there are few analyses of this surgery with a follow-up of more than 1 year,we conducted this study in order to quantitatively investigate radiographic and clinical efficacies of this surgery for central lumbar spinal stenosis.

Materials and methods

Forty-six patients with central lumbar spinal stenosis were enrolled from January 2017 to July 2018. The visual analog scale (VAS) for back pain and leg pain, Oswestry disability index (ODI), modified MacNab criteria were used to evaluate clinical efficiency at preoperative and postoperative time points. The intervertebral height index (IHI), cross-sectional area of the spinal canal (CSAC), calibrated disc signal (CDS) and spinal stability were examined to assess radiographic decompression efficiency via magnetic resonance imaging and X-ray at preoperative and postoperative time points.

Results

The VAS score for lower back pain and leg pain improved from 7.50 ± 0.78 to 1.70 ± 0.66 and from 7.30 ± 0.79 to 1.74 ± 0.68, respectively, and the ODI improved from 72.35 ± 8.15 to 16.15 ± 4.51. In terms of modified MacNab criteria, 91.3% of the patients achieved good or excellent outcomes. Furthermore, significant changes after surgery were observed for the percentage of CSAC, increasing from 125.3 ± 53.9 to 201.4 ± 78 mm2; however, no significant differences were observed for the remaining measurement indicators.

Conclusions

The clinical and radiographic efficacies of this surgery for central lumbar spinal stenosis were good in short-term follow-up, and this surgery did not cause meaningful changes in IHI, CDS, and spine stability in short-term follow-up. The effect of long-term follow-up needs further investigation.
Mining of two novel aldehyde dehydrogenases (DHY-SC-VUT5 and DHY-G-VUT7) from metagenome of hydrocarbon contaminated soils
Authors: Baburam Cindy , Feto Naser Aliye
Published: March 2021

Background

Aldehyde dehydrogenases are vital for aerobic hydrocarbon degradation and is involved in the last step of catalysing the oxidation of aldehydes to carboxylic acids. With the global increase in hydrocarbon pollution of different environments, these enzymes have the potential to be used in enzymatic bioremediation applications.

Results

Fifteen fosmid clones with hydrocarbon degrading potential were functionally screened to identify dehydrogenase enzymes. Accordingly, the fosmid insert of the positive clones were sequenced using PacBio next generation sequencing platform and de novo assembled using CLC Genomic Work Bench. The 1233 bp long open reading frame (ORF) for DHY-SC-VUT5 was found to share a protein sequence similarity of 97.7% to short-chain dehydrogenase from E. coli. The 1470 bp long ORF for DHY-G-VUT7 was found to share a protein sequence similarity of 23.9% to glycine dehydrogenase (decarboxylating) (EC 1.4.4.2) from Caulobacter vibrioides (strain NA1000 / CB15N) (Caulobacter crescentus). The in silico analyses and blast against UNIPROT protein database with the stated similarity show that the two dehydrogenases are novel. Biochemical characterization revealed, that the highest relative activity was observed at substrate concentrations of 150 mM and 50 mM for DHY-SC-VUT5 and DHY-G-VUT7, respectively. The Km values were found to be 13.77 mM with a Vmax of 0.009135 μmol.min− 1 and 2.832 mM with a Vmax of 0.005886 μmol.min− 1 for DHY-SC-VUT5 and DHY-G-VUT7, respectively. Thus, a potent and efficient enzyme for alkyl aldehyde conversion to carboxylic acid.

Conclusion

The microorganisms overexpressing the novel aldehyde dehydrogenases could be used to make up microbial cocktails for biodegradation of alkanes. Moreover, since the discovered enzymes are novel it would be interesting to solve their structures by crystallography and explore the downstream applications.
Factors associated with delay in seeking treatment among women with pelvic organ prolapse at selected general and referral hospitals of Southern Ethiopia, 2020
Authors: Borsamo Asfaw , Oumer Mohammed , Asmare Yared , Worku Ayanaw
Published: March 2021

Background

Pelvic organ prolapse (POP) is the descent of the vaginal wall, cervix, uterus, bladder, and rectum downward into the vaginal canal. Its prevalence is higher among women in developing countries because women are more prone to risk factors. In Ethiopia, women with prolapse seek treatments at advanced stages of prolapse; hence, surgical management has been widely practicing. Therefore, it was found to be very important to conduct research that assesses factors hindering early treatments in Southern Ethiopia. This study aimed to find out factors associated with the delay in seeking treatment of pelvic organ prolapse among patients at selected general and referral hospitals of Southern Ethiopia.

Methods

Cross-sectional study design was employed in 123 participants of seven randomly selected General and Referral Hospitals of Southern Ethiopia from February 01 to April 30, 2020, by using a structured questionnaire. Pre-trained two midwives in each center were deployed to collect data. Physicians performed diagnosis and physical examination. Data were entered and coded using EPI INFO version 7 and exported into SPSS version 25 for analysis. Bivariate and multivariable logistic regression analyses were performed. The goodness of fit was assessed by using the Hosmer and Lemeshow goodness test.

Results

In this study, out of 123 clinically diagnosed POP cases, nearly half of them were stage III, and over one-third were stage IV. Therefore, 84.6% (104 participants) of the respondents were delayed for the treatment of POP. The mean length of delay for POP treatments was 36.41 ± 3.95 months. After adjusting for covariates, lack of supports [AOR (Adjusted Odds Ratio) = 5.2 (95% CI 1.4–19.5)], low-income [AOR = 5.8 (95% CI 1.1–19.66)], and fear of social stigma [AOR = 4.7 (95% CI 1.2–18.59)] were significant factors for delayed treatments.

Conclusions

Most of the POP patients were delayed for POP treatments. Factors like lack of support, low-income, and fear of losing social value/stigma were associated with treatment delay. Screening for the POP cases, educating (making awareness) the community about this devastating disease to facilitate early treatment and to avoid social stigma, and raising access to treatment by making the nearby hospitals equipped with facilities to treat POP are recommended.
Willingness to volunteer and readiness to practice of undergraduate medical students during the COVID-19 pandemic: a cross-sectional survey in Indonesia
Authors: Lazarus Gilbert , Findyartini Ardi , Putera Azis Muhammad , Gamalliel Nico , Nugraha David , Adli Imam , Phowira Jason , Azzahra Lyanna , Ariffandi Bagas , Widyahening Indah Suci
Published: March 2021

Background

The question to involve or restrict medical students’ involvement in the coronavirus disease 2019 (COVID-19) pandemic response remains contentious. As their state of preparation and perceptions in volunteering during this pandemic have yet to be investigated, this study aims to evaluate Indonesian medical students’ willingness to volunteer and readiness to practice during the COVID-19 pandemic.

Methods

A web-based survey was conducted among undergraduate medical students throughout Indonesia. Socio-demographic and social interaction information, in addition to willingness to volunteer and readiness to practice, were obtained using a self-reported questionnaire. The significance level was set at 5%.

Results

Among 4870 participants, 2374 (48.7%) expressed their willingness to volunteer, while only 906 (18.6%) had adequate readiness to practice. Male students, students with prior volunteering experience in health or non-health sectors, and students from public universities or living in Central Indonesia (vs Java) had higher scores of willingness and readiness to volunteer. Students from Sumatra also had better preparedness (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.15–2.12, p = 0.004), while the opposite occurred for students from Eastern Indonesia (OR 0.63, 95% CI: 0.44–0.89, p = 0.002)–when compared to students from Java. In addition, compared to students with high family income, students from lower-middle income families were less willing to volunteer (OR 0.76, 95% CI: 0.59–0.98, p = 0.034), though those with low family income had better readiness (OR 1.51, 95% CI: 1.10–2.08, p = 0.011). Shortage of medical personnel, sense of duty, and solicitation by stakeholders were the main reasons increasing the students’ willingness to volunteer; whereas contrarily fear for own’s health, absence of a cure, and fear of harming patients were the primary factors diminishing their willingness to volunteer.

Conclusion

Our findings indicated that many Indonesian medical students are willing to volunteer, yet only few of them were ready to practice, indicating that further preparations are required to maximize their potentials and minimize their exposure to hazards. We suggest that their potentials as a firm support system during the pandemic should not be overlooked, and that the integration of relevant courses to the medical curricula are imperative to prepare for future public health emergencies.
Disclosure of clinically actionable genetic variants to thoracic aortic dissection biobank participants
Authors: Beil Adelyn , Hornsby Whitney , Uhlmann Wendy R. , Aatre Rajani , Arscott Patricia , Wolford Brooke , Eagle Kim A. , Yang Bo , McNamara Jennifer , Willer Cristen , Roberts J. Scott
Published: March 2021

Background

Disclosure of pathogenic variants to thoracic aortic dissection biobank participants was implemented. The impact and costs, including confirmatory genetic testing in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, were evaluated.

Methods

We exome sequenced 240 cases with thoracic aortic dissection and 258 controls, then examined 11 aortopathy genes. Pathogenic variants in 6 aortopathy genes (COL3A1,FBN1,LOX,PRKG1,SMAD3, andTGFBR2)were identified in 26 participants, representing 10.8% of the cohort (26/240). A second research sample was used to validate the initial findings. Mailed letters to participants disclosed that a potentially disease causing DNA alteration had been identified (neither the gene nor variant was disclosed). Participants were offered clinical genetic counseling and confirmatory genetic testing in a CLIA laboratory.

Results

Excluding 6 participants who were deceased or lost to follow-up, 20 participants received the disclosure letter, 10 of whom proceeded with genetic counseling, confirmatory genetic testing, and enrolled in a survey study. Participants reported satisfaction with the letter (4.2 ± 0.7) and genetic counseling (4.4 ± 0.4; [out of 5, respectively]). The psychosocial impact was characterized by low decisional regret (11.5 ± 11.6) and distress (16.0 ± 4.2, [out of 100, respectively]). The average cost for 26 participants was $400, including validation and sending letters. The average cost for those who received genetic counseling and CLIA laboratory confirmation was $605.

Conclusions

Participants were satisfied with the return of clinically significant biobank genetic results and CLIA laboratory testing; however, the process required significant time and resources. These findings illustrate the trade-offs involved for researchers considering returning research genetic results.
Differential ketogenic diet-induced shift in CSF lipid/carbohydrate metabolome of pediatric epilepsy patients with optimal vs. no anticonvulsant response: a pilot study
Authors: Masino Susan A. , Ruskin David N. , Freedgood Natalie R. , Lindefeldt Marie , Dahlin Maria
Published: March 2021

Background

The low carbohydrate, high fat ketogenic diet can be an effective anticonvulsant treatment in some pediatric patients with pharmacoresistant epilepsy. Its mechanism(s) of action, however, remain uncertain. Direct sampling of cerebrospinal fluid before and during metabolic therapy may reveal key changes associated with differential clinical outcomes. We characterized the relationship between seizure responsiveness and changes in lipid and carbohydrate metabolites.

Methods

We performed metabolomic analysis of cerebrospinal fluid samples taken before and during ketogenic diet treatment in patients with optimal response (100% seizure remission) and patients with no response (no seizure improvement) to search for differential diet effects in hallmark metabolic compounds in these two groups. Optimal responders and non-responders were similar in age range and included males and females. Seizure types and the etiologies or syndromes of epilepsy varied but did not appear to differ systematically between responders and non-responders.

Results

Analysis showed a strong effect of ketogenic diet treatment on the cerebrospinal fluid metabolome. Longitudinal and between-subjects analyses revealed that many lipids and carbohydrates were changed significantly by ketogenic diet, with changes typically being of larger magnitude in responders. Notably, responders had more robust changes in glucose and the ketone bodies β-hydroxybutyrate and acetoacetate than non-responders; conversely, non-responders had significant increases in fructose and sorbose, which did not occur in responders.

Conclusions

The data suggest that a differential and stronger metabolic response to the ketogenic diet may predict a better anticonvulsant response, and such variability is likely due to inherent biological factors of individual patients. Strategies to boost the metabolic response may be beneficial.
Sialolithiasis: retrospective analysis of the effect of an escalating treatment algorithm on patient-perceived health-related quality of life
Authors: Lommen Julian , Schorn Lara , Roth Benjamin , Naujoks Christian , Handschel Jörg , Holtmann Henrik , Kübler Norbert R. , Sproll Christoph
Published: March 2021

Background

Gland preserving techniques in the treatment of sialolithiasis have continuously replaced radical surgery. The aim of this study was to evaluate a multimodal treatment algorithm in the therapy of sialolithiasis and assess improvement of HRQoL perceived by patients.

Methods

Patients with sialolithiasis were treated by a multimodal treatment algorithm based on multiplicity of stones, stone size, affected gland, and stone position. The therapeutic spectrum ranged from conservative measures, extracorporeal shockwave lithotripsy, interventional sialendoscopy, combined endoscopic-surgical procedures to surgical gland removal as ultima ratio. Outcomes were evaluated by surgeons by means of the electronic patient record and by patients themselves using a standardized questionnaire.

Results

87 patients treated for sialolithiasis were comprised in this study. The submandibular gland (SMG) was affected in 58.6% and the parotid gland (PG) in 41.4% of cases. Mean patient age was 41.67 years for SMG and 48.91 years for PG. In over 80% of cases sialolithiasis was associated with classic meal-related pain and swelling. Type and intensity of symptomatic sialolithiasis were not dependent on patient age or gender, nor could a relation between the affected gland and the occurrence of symptoms be demonstrated. Overall, 86.2% of cases were reported as cured using the multimodal step-by-step treatment algorithm. Resection of the affected gland could be dispensed in 98.9% of cases. According to patients pain could be reduced in 94.3% of cases.

Conclusions

The analyzed treatment algorithm of increasing invasiveness is a favorable and effective tool to successfully treat sialolithiasis in > 86% of cases. For the first time, the present study shows that patient-perceived improvement of HRQoL due to ease of symptoms has an even higher success rate of > 94%.
A comprehensive review of hydroxyurea for β-haemoglobinopathies: the role revisited during COVID-19 pandemic
Authors: Yasara Nirmani , Premawardhena Anuja , Mettananda Sachith
Published: March 2021

Background

Hydroxyurea is one of the earliest drugs that showed promise in the management of haemoglobinopathies that include β-thalassaemia and sickle cell disease. Despite this, many aspects of hydroxyurea are either unknown or understudied; specifically, its usefulness in β-thalassaemia major and haemoglobin E β-thalassaemia is unclear. However, during COVID-19 pandemic, it has become a valuable adjunct to transfusion therapy in patients with β-haemoglobinopathies. In this review, we aim to explore the available in vitro and in vivo mechanistic data and the clinical utility of hydroxyurea in β-haemoglobinopathies with a special emphasis on its usefulness during the COVID-19 pandemic.

Main body

Hydroxyurea is an S-phase-specific drug that reversibly inhibits ribonucleoside diphosphate reductase enzyme which catalyses an essential step in the DNA biosynthesis. In human erythroid cells, it induces the expression of γ-globin, a fetal globin gene that is suppressed after birth. Through several molecular pathways described in this review, hydroxyurea exerts many favourable effects on the haemoglobin content, red blood cell indices, ineffective erythropoiesis, and blood rheology in patients with β-haemoglobinopathies. Currently, it is recommended for sickle cell disease and non-transfusion dependent β-thalassaemia. A number of clinical trials are ongoing to evaluate its usefulness in transfusion dependent β-thalassaemia. During the COVID-19 pandemic, it was widely used as an adjunct to transfusion therapy due to limitations in the availability of blood and logistical disturbances. Thus, it has become clear that hydroxyurea could play a remarkable role in reducing transfusion requirements of patients with haemoglobinopathies, especially when donor blood is a limited resource.

Conclusion

Hydroxyurea is a well-tolerated oral drug which has been in use for many decades. Through its actions of reversible inhibition of ribonucleoside diphosphate reductase enzyme and fetal haemoglobin induction, it exerts many favourable effects on patients with β-haemoglobinopathies. It is currently approved for the treatment of sickle cell disease and non-transfusion dependent β-thalassaemia. Also, there are various observations to suggest that hydroxyurea is an important adjunct in the treatment of transfusion dependent β-thalassaemia which should be confirmed by randomised clinical trials.
Pre-positioning an evaluation of cash assistance programming in an acute emergency: strategies and lessons learned from a study in Raqqa Governorate, Syria
Authors: Falb Kathryn , Annan Jeannie
Published: March 2021

Background

Conducting ethical and rigorous research to measure the effectiveness of humanitarian programs is urgently needed given the global level of displacement and conflict, yet traditional approaches to evaluation research may be too slow and disruptive for acute humanitarian settings. The current case study utilizes an experience of implementing a mixed methods evaluation conducted between March–August 2018 in northern Raqqa Governorate, Syria. The key research objectives were to examine the influence of an unconditional, three-month cash transfer program on household basic needs and women’s wellbeing, including experiences of violence. This setting was selected for the research as it shared many aspects of an acute emergency within a protracted conflict given its recent opening of access to humanitarian aid programming following the withdrawal of ISIS as well as influxes of internally displaced persons fleeing airstrikes and fighting in Raqqa City in late 2017.

Discussion

The current case study was scientifically important as the use of cash assistance in emergencies has increased exponentially in recent years. Yet, little is still known about how cash assistance designed to help households meet their basic needs may also influence women’s overall wellbeing in the home. Challenges of conducting the research included selecting an emergency site appropriate for research, implementing an evaluation that would not delay or disrupt critical cash assistance programming, and measurement of sensitive violence against women outcomes. Four strategies were identified to meet the challenges of conducting an evaluation in such a setting, which included: (1) developing clear decision-making criteria for assessing feasibility; (2) frontloading processes to reduce time lag in launching research; (3) integrating the research approach within programming; and (4) closely collaborating with practitioners throughout the study, especially for research on sensitive topics like violence against women. Conclusions

Advance consideration of these factors through a pre-positioning process will allow for timely, ethical, and rigorous research to be implemented in the immediate aftermath of a crisis. Such studies should be prioritized to ensure the highest effectiveness and efficiency of humanitarian aid for populations grappling with acute emergencies.
Cancer-associated fibroblasts promote the survival of irradiated nasopharyngeal carcinoma cells via the NF-κB pathway
Authors: Huang Weiqiang , Zhang Longshan , Yang Mi , Wu Xixi , Wang Xiaoqing , Huang Wenqi , Yuan Lu , Pan Hua , Wang Yin , Wang Zici , Wu Yuting , Huang Jihong , Liang Huazhen , Li Shaoqun , Liao Liwei , Liu Laiyu , Guan Jian
Published: March 2021

Background

Irradiation has emerged as a valid tool for nasopharyngeal carcinoma (NPC) in situ treatment; however, NPC derived from tissues treated with irradiation is a main cause cancer-related death. The purpose of this study is to uncover the underlying mechanism regarding tumor growth after irradiation and provided potential therapeutic strategy.

Methods

Fibroblasts were extracted from fresh NPC tissue and normal nasopharyngeal mucosa. Immunohistochemistry was conducted to measure the expression of α-SMA and FAP. Cytokines were detected by protein array chip and identified by real-time PCR. CCK-8 assay was used to detect cell proliferation. Radiation-resistant (IRR) 5-8F cell line was established and colony assay was performed to evaluate tumor cell growth after irradiation. Signaling pathways were acquired via gene set enrichment analysis (GSEA). Comet assay and γ-H2AX foci assay were used to measure DNA damage level. Protein expression was detected by western blot assay. In vivo experiment was performed subcutaneously.

Results

We found that radiation-resistant NPC tissues were constantly infiltrated with a greater number of cancer-associated fibroblasts (CAFs) compared to radiosensitive NPC tissues. Further research revealed that CAFs induced the formation of radioresistance and promoted NPC cell survival following irradiation via the IL-8/NF-κB pathway to reduce irradiation-induced DNA damage. Treatment with Tranilast, a CAF inhibitor, restricted the survival of CAF-induced NPC cells and attenuated the of radioresistance properties.

Conclusions

Together, these data demonstrate that CAFs can promote the survival of irradiated NPC cells via the NF-κB pathway and induce radioresistance that can be interrupted by Tranilast, suggesting the potential value of Tranilast in sensitizing NPC cells to irradiation.
Effect of patient-controlled intravenous analgesia combined with flurbiprofen axetil and dezocine on postoperative analgesia for lobectomy (EPIC-FAD): a trial protocol
Authors: Zhou Jian , Pu Qiang , Lin Lin , Chong Weelic , Chen Boran , Hai Yang , Liu Fei , Liu Lunxu
Published: March 2021

Background

The optimal analgesic strategy for surgical pain after lobectomy remains undefined. To compare the combination of flurbiprofen axetil and dezocine with flurbiprofen axetil alone and dezocine alone, in post-lobectomy patients.

Methods

A single-center, parallel-design double-blind superiority trial, with 5 groups (1:1:1:1:1 ratio) with different combinations of flurbiprofen and dezocine. Patients scheduled for lobectomy will be recruited. The primary outcome is total sufentanil use in patient-controlled intravenous analgesia within the first 24 postoperative hours. Secondary outcomes include pain numeric rating scales at 6th, 12th, 24th, 48th, and 72th postoperative hours, and on the 1st, 3rd, and 6th postoperative months at rest and during coughing, adverse effects from experimental drug treatment, sufentanil use at other time points, analgesia cost, time to chest tube removal, length of hospital stay, time to pass first flatus, and serum level of cytokines. Doctors, patients, and nurses are blinded, and only the manager is unblinded. Analysis is intention-to-treat. Statistical analysis is pre-specified. Statistical comparison of the treatment groups includes one-way analysis of variance followed by Tukey’s post hoc test.

Discussion

Trial did not begin to recruit. Participant recruitment start date is planned to be June 1, 2020. Approximate recruitment end date is May 31, 2021. If successful, the trial may shed light on the use of certain analgesic combinations in post-lobectomy pain control.

Trial registration

Chinese Clinical Trial Registry ChiCTR1800018563. Registered on September 25, 2018.
Effect of early treatment with polyvalent immunoglobulin on acute respiratory distress syndrome associated with SARS-CoV-2 infections (ICAR trial): study protocol for a randomized controlled trial
Authors: Mazeraud Aurélien , Gonçalves Bruno , Aegerter Philippe , Mancusi Letizia , Rieu Christine , Bozza Fernando , Sylla Khaoussou , Siami Shidasp , Sharshar Tarek
Published: March 2021

Background

As of mid-June 2020, 7,500,000 people were infected with SARS-CoV-2 worldwide and 420,000 people died, mainly from coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). COVID-19-related ARDS is subject to a mortality rate of 50% and prolonged period of mechanical ventilation, with no specific pharmacological treatment currently available (Infection au nouveau Coronavirus (SARS-CoV-2), COVID-19, France et Monde. https://www.santepubliquefrance.fr/dossiers/coronavirus-covid-19). Because of its immunomodulatory action, we propose to evaluate the efficacy and safety of intravenous immunoglobulin (IVIG) administration in patients developing COVID-19-related ARDS.

Methods

The trial is a phase III double-blind, randomized, multicenter, parallel group, concurrent, controlled study in hospitalized participants with COVID-19 requiring mechanical ventilation using a sequential design. Participants in the treatment group will receive infusions of polyvalent immunoglobulin for 4 consecutive days, and the placebo group will receive an equivalent volume of sodium chloride 0.9% for the same duration. The primary outcome is the number of ventilator-free days up to the 28th day. Secondary objectives are to evaluate the effect of IVIG on (1) organ failure according to the Sequential Organ Failure Assessment (SOFA) score at 14 and 28 days, (2) lung injury score at 14 and 28 days, (3) the occurrence of grade 3 or 4 adverse events of IVIG, (4) length of intensive care unit (ICU) stay, (5) length of hospital stay, (6) functional outcomes at day 90 defined by the activities of daily living and instrumental activities of the daily living scales, and (7) 90-day survival. One hundred thirty-eight subjects will be randomized in a 1:1 ratio to IVIG or placebo groups (69 in each group), considering 90% power, alpha level 0.05 (two sides), and 0.67 effect size level.

Discussion

The ICAR trial investigates the effect of IVIG in COVID-19-related ARDS. We expect an increase in the survival rate and a reduction in the duration of mechanical ventilation, which is associated with significant morbidity.

Trial registration

EudraCT 2020-001570-30. ClinicalTrials.gov NCT04350580. Registered on 17 April 2020
UKCTOCS update: applying insights of delayed effects in cancer screening trials to the long-term follow-up mortality analysis
Authors: Burnell Matthew , Gentry-Maharaj Aleksandra , Skates Steven J. , Ryan Andy , Karpinskyj Chloe , Kalsi Jatinderpal , Apostolidou Sophia , Singh Naveena , Dawnay Anne , Woolas Robert , Fallowfield Lesley , Campbell Stuart , McGuire Alistair , Jacobs Ian J. , Parmar Mahesh , Menon Usha
Published: March 2021

Background

During trials that span decades, new evidence including progress in statistical methodology, may require revision of original assumptions. An example is the continued use of a constant-effect approach to analyse the mortality reduction which is often delayed in cancer-screening trials. The latter led us to re-examine our approach for the upcoming primary mortality analysis (2020) of long-term follow-up of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (LTFU UKCTOCS), having initially (2014) used the proportional hazards (PH) Cox model.

Methods

We wrote to 12 experts in statistics/epidemiology/screening trials, setting out current evidence, the importance of pre-specification, our previous mortality analysis (2014) and three possible choices for the follow-up analysis (2020) of the mortality outcome: (A) all data (2001–2020) using the Cox model (2014), (B) new data (2015–2020) only and (C) all data (2001–2020) using a test that allows for delayed effects.

Results

Of 11 respondents, eight supported changing the 2014 approach to allow for a potential delayed effect (option C), suggesting various tests while three favoured retaining the Cox model (option A). Consequently, we opted for the Versatile test introduced in 2016 which maintains good power for early, constant or delayed effects. We retained the Royston-Parmar model to estimate absolute differences in disease-specific mortality at 5, 10, 15 and 18 years.

Conclusions

The decision to alter the follow-up analysis for the primary outcome on the basis of new evidence and using new statistical methodology for long-term follow-up is novel and has implications beyond UKCTOCS. There is an urgent need for consensus building on how best to design, test, estimate and report mortality outcomes from long-term randomised cancer screening trials.

Trial registration

ISRCTN22488978. Registered on 6 April 2000.
Label information and consumer behaviour: evidence on drinking milk sector
Authors: Marchini Andrea , Riganelli Chiara , Diotallevi Francesco , Polenzani Bianca
Published: March 2021

The purpose of the research is to evaluate the impact of different kinds of information disclosures of milk labels, investigating the interest among consumers based on their consumption behaviours and characteristics. In this research, all the actions which lead to a healthiness, become expressions of a production process, among which consumers’ food choices, purchase, preparation, and also self-production. Therefore, in the “health creation” production process, information and knowledge about food become “investments”. In this context, label disclosures become a tangible expression of this kind of “investment”. The research question is: what impact do purchase preferences and consumers’ characteristics have on their interest towards the label information provided? Several information disclosures, both mandatory and voluntary, are investigated. Therefore, some choice attributes will be analysed as indicators of the consumer’s behaviour in relation to his investment in food information. The methodology used for the analysis is an Ordered Logit. The analysis of the consumer’s behaviour has been performed by transposing Ménard’s analysis of firm corporate governance (Ménard, Agribus. 34:142–160, 2018) to the consumer as producer of welfare equity. The reduction of information asymmetry is a cost for the producer, and this research may be able to measure how much it would be convenient to invest in this reduction, based on the analysis of the consumer’s behaviour toward his personal investment in food information acquisition.
Real-time data assimilation and control on mechanical systems under uncertainties
Authors: Rubio Paul-Baptiste , Chamoin Ludovic , Louf François
Published: March 2021

This research work deals with the implementation of so-called Dynamic Data-Driven Application Systems (DDDAS) in structural mechanics activities. It aims at designing a real-time numerical feedback loop between a physical system of interest and its numerical simulator, so that (i) the simulation model is dynamically updated from sequential and in situ observations on the system; (ii) the system is appropriately driven and controlled in service using predictions given by the simulator. In order to build such a feedback loop and take various uncertainties into account, a suitable stochastic framework is considered for both data assimilation and control, with the propagation of these uncertainties from model updating up to command synthesis by using a specific and attractive sampling technique. Furthermore, reduced order modeling based on the Proper Generalized Decomposition (PGD) technique is used all along the process in order to reach the real-time constraint. This permits fast multi-query evaluations and predictions, by means of the parametrized physics-based model, in the online phase of the feedback loop. The control of a fusion welding process under various scenarios is considered to illustrate the proposed methodology and to assess the performance of the associated numerical architecture.
Understanding why apprentices consider dropping out: longitudinal prediction of apprentices’ workplace interest and anxiety
Authors: Powers Tim E. , Watt Helen M. G.
Published: March 2021

Although apprenticeships ease the school-to-work transition for youth, many apprentices seriously consider dropping out. While associated with noncompletions, dropout considerations are important to study in their own right, because they reflect a negative quality of apprenticeship experience and can impact apprentices’ quality of learning and engagement. Few studies have addressed apprentices’ dropout considerations using comprehensive theoretical frameworks. To address this gap, this study examined how apprentices’ interest and anxiety growth trajectories predicted dropout considerations and associated with perceived resources and demands, grounded in expectancy-value theory (EVT) and the job demands-resources (JD-R) model. Australian apprentices (N = 2387) were surveyed at 6-month intervals utilising an accelerated longitudinal design, on their workplace interest and anxiety, job-related resources (role model, timing of choice, employer teaching, expertise, job security, and training wages) and demands (lack of information, career indecision, and excessive work). Latent growth models (LGM) within a structural equation modelling framework showed apprentices began with high interest which declined over time, and low anxiety which increased in the latter half of their first year until the end of their second year. Apprentices’ dropout considerations were predicted by initial interest and anxiety levels (at the beginning of their apprenticeship), and by interest losses during their apprenticeship (but, not by increases in anxiety). Almost half the variance in interest and anxiety trajectories was explained by apprentices’ perceived resources and demands: resources had a greater effect on promoting interest than reducing anxiety, whereas demands were more important in exacerbating anxiety.
Research under the GDPR – a level playing field for public and private sector research?
Authors: Quinn Paul
Published: March 2021

Scientific research is indispensable inter alia in order to treat harmful diseases, address societal challenges and foster economic innovation. Such research is not the domain of a single type of organization but can be conducted by a range of different entities in both the public and private sectors. Given that the use of personal data may be indispensable for many forms of research, the data protection framework will play an important role in determining not only what types of research may occur but also which types of actors may carry it out. This article looks at the role the EU’s General Data Regulation plays in determining which types of actors can conduct research with personal data. In doing so it focuses on the various legal bases that are available and attempts to discern whether the GDPR can be said to favour research in either the public or private domains. As this article explains, the picture is nuanced, with either type of research actor enjoying advantages and disadvantages in specific contexts.
Structural, functional, and evolutionary analysis of Cry toxins of Bacillus thuringiensis: an in silico study
Authors: Das Sujit Kumar , Pradhan Sukanta Kumar , Samal Kailash Chandra , Singh Nihar Ranjan
Published: March 2021

Background

Bacillus thuringiensis (Bt) is a gram-positive spore-forming soil bacterium that synthesizes crystalline (Cry) protein, which is toxic and causing pathogenicity against mainly three insect orders: Coleoptera, Diptera, and Lepidoptera. These crystalline protein inclusions, i.e., δ-endotoxins are successfully used as a bio-control agent against insect pests.

Main body

A total of 58 various Cry proteins belonging to these 3 insect orders were retrieved from SwissProt database and are categorized into different groups. Structural and functional analysis were performed to understand the functional domain arrangements at sequence level as well as at structural level involving both experimental and predicted 3-dimensional models. Besides, the analysis of evolutionary relationship involving all 58 observed Cry proteins at the sequence, domain, and structural levels were done using different bioinformatics tools. Evolutionary analysis revealed that some Cry proteins having toxicity for a specific insect order are found to be clustered for another different insect order, which concludes that they might have toxicity for more than one insect order. Three-dimensional (3D) structure analysis of both experimental and predicted models revealed that proteins might have toxicity for a specific insect order differ in their structural arrangements and was observed in Cry proteins belonging to 3 different insect orders.

Conclusions

It could be hypothesized that an inner-molecular domain shift or domain insertion/deletion might have taken place during the evolutionary process, which consequently causes structural and functional divergence of Bt. The study output may be helpful for understanding the diversity as well as specificity of the analyzed insecticidal proteins and their application as a biopesticide in the field of agriculture.
A language to analyze, describe, and explore collections of visual art
Authors: Pflüger Hermann
Published: March 2021

A vast quantity of art in existence today is inaccessible to individuals. If people want to know the different types of art that exist, how individual works are connected, and how works of art are interpreted and discussed in the context of other works, they must utilize means other than simply viewing the art. Therefore, this paper proposes a language to analyze, describe, and explore collections of visual art (LadeCA). LadeCA combines human interpretation and automatic analyses of images, allowing users to assess collections of visual art without viewing every image in them. This paper focuses on the lexical base of LadeCA. It also outlines how collections of visual art can be analyzed, described, and explored using a LadeCA vocabulary. Additionally, the relationship between LadeCA and indexing systems, such as ICONCLASS or AAT, is demonstrated, and ways in which LadeCA and indexing systems can complement each other are highlighted.