bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection of Construction Bidders Using the Analytical Hierarchy Process and Friedman Theory
Authors: Salman Alaa
Published: January 2022

Selecting a suitable bidder to execute a construction project is not an easy task, especially for the short bidder list. The consequences of the selection might affect the project performance in terms of cost, money, and quality. The current research in this work deals with the selection of a contractor, who bids on a specific project. The historical data of contractors are a key of the selection based on three approaches: the quick selection approach (QSA), generic selection approach (GSA), and comprehensive selection approach (CSA). The QSA relies on the scoring system according to delay factors. The QSA is the weighted average of the delay factors using the analytical hierarchy process (AHP), the CSA is based on the integrated QSA and the bidding strategy using Friedman’s theory. The current three approaches can be utilized by public and private owners, who intend to select a general contractor to execute new construction projects. A hypothetical case study is implemented to demonstrate the developed models. Several experts in the field of construction management have confirmed the findings. The third strategy (CSA) is found to be the most appropriate for selecting construction bidders.
Piloting an Intervention to Improve Outcomes in Young Adults Living With Type 1 Diabetes: The Experience of the D1 Now Support Worker
Authors: Lowry Michelle , Morrissey Eimear C. , Dinneen Sean F.
Published: January 2022

Introduction

D1 Now is a novel intervention which aims to support self-management and clinic engagement and improve outcomes in young adults (18-25 years) living with type 1 diabetes in Ireland. It has been developed using a systematic, theoretical, user-centred approach. The specific role of the Support Worker, one of three components of the D1 Now intervention, was developed to provide continuity and build relationships between young adults and their diabetes team.

Methods

A Support Worker - an Occupational Therapist, who had a background in youth mental health - was hired as part of the D1 Now pilot randomised controlled trial and was based in one intervention site to join the existing diabetes team.

Discussion

The Support Worker aimed to provide an accessible and consistent point of contact for young adults, facilitated conversations about distress, and encouraged graded goal setting and collaborative problem solving. The role afforded her with a unique window into the lived experiences of young adults with type 1 diabetes where she observed the ongoing negotiation of life and living alongside diabetes care and management. The prevalence of diabetes distress was high in the study cohort with particular challenges associated with ‘all or nothing’ thinking patterns as well as disordered eating behaviours. The Support Worker also played an advocacy role in supporting the diabetes team’s awareness of young adults’ needs and explored current barriers to care. Preliminary findings from the D1 Now pilot have identified that the role of the Support Worker was viewed positively from the perspective of young adults with type 1 diabetes.
Positive Correlation Between LTA Expression and Overall Immune Activity Suggests an Increased Probability of Survival in Uterine Corpus Endometrial Carcinoma
Authors: Shi Mingjie , Luo Fei , Shao Taotao , Zhang Hengli , Yang Taili , Wei Yue , Chen Riling , Guo Runmin
Published: January 2022

Mounting evidence indicates that immune status plays a crucial role in tumor progress and metastasis, while there are no effective and easily assayed biomarkers to reflect it in uterine corpus endometrial carcinoma (UCEC) patients. Here, we attempted to identify the potential biomarkers that were differentially expressed between normal and tumor tissues and involved in prognosis and immune microenvironment of UCEC patients. RNA-seq data with relevant clinical information were obtained from The Cancer Genome Atlas (TCGA). ssGSEA algorithm was applied to calculate the enrichment scores of every tumor infiltration lymphocyte (TIL) set in each sample, and patients were then divided into three clusters using multiple R packages. Cox analysis, ESTIMATE, and CIBERSORT were utilized to determine the differentially expressed immune-related genes (DEIGs) with overall survival, and to explore their roles in prognosis, immune microenvironment, and immunotherapeutic response. The TIMER and TISIDB databases were utilized to predict the effectiveness of immunotherapy in UCEC patients. LTA was finally identified to be significantly upregulated in tumor tissues and closely associated with prognosis and immunological status, which was then verified in GSE17025. In multivariate analysis, the hazard ratio of LTA was 0.42 with 95% CI (0.22–0.80) (p = 0.008). Patients with high LTA expression had better survival and apparently immune-activated phenotypes, such as more tumor mutation burden (TMB), stronger immune cell infiltrations, higher expression of immunosuppressive points, and higher immunophenoscore, meaning they had an immunotherapeutic advantage over those with low LTA expression. TIMER and TISIDB indicated that LTA was highly expressed in UCEC, and its expression was negatively correlated with stages and positively related to prognosis. Additionally, we found that LTA ectopic expression weakened the proliferation ability of RL95-2 cells. All these findings indicated that LTA could act as a novel and easily assayed biomarker to predict immunological status and clinical outcomes and even as an antioncogene to explore UCEC in depth.
Process Improvement of Adeno-Associated Virus Production
Authors: Guan Jia-Shiung , Chen Kai , Si Yingnan , Kim Taehyun , Zhou Zhuoxin , Kim Seulhee , Zhou Lufang , Liu Xiaoguang
Published: January 2022

Adeno-associated viruses (AAVs) have been well characterized and used to deliver therapeutic genes for diseases treatment in clinics and basic research. This study used the triple transient transfection of AAV-DJ/8 as a model expression system to develop and optimize the laboratory production of AAV for research and pre-clinical applications. Specifically, various production parameters, including host cell, transfection reagent, cell density, ratio of plasmid DNA and cells, gene size, and production mode, were tested to determine the optimal process. Our results showed that the adherent production using HEK 293AAV with calcium transfection generated the highest volumetric productivity of 7.86 × 109 gc/ml. The optimal suspensive production using HEK 293F had best AAV productivity of 5.78 × 109 gc/ml in serum-free medium under transfection conditions of transfection density of 0.4 × 106 cells/ml, plasmid DNA:cells ratio of 1.6 µg:106 cells and synthesized cationic liposomes as transfection reagent. The similar AAV productivity was confirmed at scales of 30–450 ml in shaker and/or spinner flasks. The in vitro transfection and in vivo infection efficiency of the harvested AAV-DJ/8 carrying luciferase reporter gene was confirmed using cell line and xenograft mouse model, respectively. The minimal or low purification recovery rate of AAV-DJ/8 in ion-exchange chromatography column and affinity column was observed in this study. In summary, we developed and optimized a scalable suspensive production of AAV to support the large-scale preclinical animal studies in research laboratories.
Review of Thin Film Nanocomposite Membranes and Their Applications in Desalination
Authors: Nambi Krishnan Jegatha , Venkatachalam Kaarthick Raaja , Ghosh Oindrila , Jhaveri Krutarth , Palakodeti Advait , Nair Nikhil
Published: January 2022

All over the world, almost one billion people live in regions where water is scarce. It is also estimated that by 2035, almost 3.5 billion people will be experiencing water scarcity. Hence, there is a need for water based technologies. In separation processes, membrane based technologies have been a popular choice due to its advantages over other techniques. In recent decades, sustained research in the field of membrane technology has seen a remarkable surge in the development of membrane technology, particularly because of reduction of energy footprints and cost. One such development is the inclusion of nanoparticles in thin film composite membranes, commonly referred to as Thin Film Nanocomposite Membranes (TFN). This review covers the development, characteristics, advantages, and applications of TFN technology since its introduction in 2007 by Hoek. After a brief overview on the existing membrane technology, this review discusses TFN membranes. This discussion includes TFN membrane synthesis, characterization, and enhanced properties due to the incorporation of nanoparticles. An attempt is made to summarize the various nanoparticles used for preparing TFNs and the effects they have on membrane performance towards desalination. The improvement in membrane performance is generally observed in properties such as permeability, selectivity, chlorine stability, and antifouling. Subsequently, the application of TFNs in Reverse Osmosis (RO) alongside other desalination alternatives like Multiple Effect Flash evaporator and Multi-Stage Flash distillation is covered.
The Role of Exosomes in the Pathophysiology of Chronic Rhinosinusitis
Authors: Mueller Sarina K.
Published: January 2022

Non-invasive biomarker analysis has made repetitive and painless sampling over time possible. Exosomes are being released from a parent cell and their cargo mirrors the cell micromilieu of the parent cell. Therefore, exosomes are promising surrogates for their parent cells. That is also why exosomes provide an improved signal-to-noise ratio. Current studies have identified valid non-invasive biomarkers that may be able to monitor disease severity. Exosomes are suggested to play an important role in interepithelial communication and are suggested to play a role in the initiation and maintenance of inflammation in CRS. They are, however, also involved simultaneously in several immunological processes including immune protection and immunosuppression. As the isolation of exosomes is time-consuming their value in everyday routine diagnostics has yet to be determined.
Age and Season Effect the Timing of Adult Worker Honeybee Infection by Nosema ceranae
Authors: Jabal-Uriel Clara , Albarracín Verónica N. , Calatayud Joaquín , Higes Mariano , Martín-Hernández Raquel
Published: January 2022

The microsporidia Nosema ceranae is an intracellular parasite of honeybees’ midgut, highly prevalent in Apis mellifera colonies for which important epidemiological information is still unknown. Our research aimed at understanding how age and season influence the onset of infection in honeybees and its development in the colony environment. Adult worker honeybees of less than 24h were marked and introduced into 6 different colonies in assays carried out in spring and autumn. Bees of known age were individually analyzed by PCR for Nosema spp. infection and those resulting positive were studied to determine the load by Real Time-qPCR. The age of onset and development of infection in each season was studied on a total of 2401 bees and the probability and the load of infection for both periods was established with two statistical models. First N. ceranae infected honeybees were detected at day 5 post emergence (p.e.; spring) and at day 4 p.e. (autumn) and in-hive prevalence increased from that point onwards, reaching the highest mean infection on day 18 p.e. (spring). The probability of infection increased significantly with age in both periods although the age variable better correlated in spring. The N. ceranae load tended to increase with age in both periods, although the age-load relationship was clearer in spring than in autumn. Therefore, age and season play an important role on the probability and the development of N. ceranae infection in honeybees, bringing important information to understand how it spreads within a colony.
Modified Taiwan Atrial Fibrillation Score for the Prediction of Incident Atrial Fibrillation
Authors: Liao Jo-Nan , Lim Su-Shen , Chen Tzeng-Ji , Tuan Ta-Chuan , Chen Shih-Ann , Chao Tze-Fan
Published: January 2022

Background

We have proposed the Taiwan AF score consisting of age, male sex, hypertension, heart failure, coronary artery disease, end-stage renal disease, and alcoholism to predict incident atrial fibrillation (AF) in Asian population. We hypothesized that the modified Taiwan AF score (mTaiwan AF score) excluding alcoholism remained useful for predicting new onset AF.

Methods

A total of 7,220,654 subjects aged ≥ 40 years without a past history of cardiac arrhythmia were identified from a national cohort, and 438,930 incident AF occurred during a 16-year follow-up with an incidence of 0.42 per 100 person-years. The mTaiwan AF score ranging between −2 and 14 and its predictive accuracy of incident AF was analyzed.

Results

The areas under the receiver operating characteristic curve (AUCs) of the mTaiwan AF scores in predicting AF are 0.861 for 1-year follow-up, 0.829 for 5-year follow-up, 0.795 for 10-year follow-up, and 0.751 for 16-year follow-up. The risk of incident AF increased from 0.05%/year for patients with a score of −2 to 6.98%/year for those having a score of 14. Patients were classified into three groups based on the tertile values of the mTaiwan AF scores—group 1 (score −2-3), group 2 (score 4-9) and group 3 (score 10-14). The annual risks of incident AF were 0.20, 1.33, and 3.36% for group 1, 2, and 3, respectively. Compared to patients in group 1, the hazard ratios of incident AF were 5.79 [95% confidence interval (CI) 3.75-7.75] for group 2 and 8.93 (95% CI 6.47-10.80) for group 3.

Conclusions

We demonstrated that the mTaiwan AF score based on age and clinical comorbidities could be used to predict incident AF in Asian population.
Blood Group O Protect End-Stage Renal Disease Patients With Dialysis From Coronary Artery Disease
Authors: Ye Zixiang , Wu Yaxin , Tu Yimin , Chen Mulei , Gao Yanxiang , Shi Linying , Li Peizhao , Xie Enmin , Guo Ziyu , Li Qing , Yu Xiaozhai , Li Yike , Niu Wenquan , Ren Jingyi , Zheng Jingang
Published: January 2022

Objective

Our study aims to investigate the role of the ABO blood group in the development and severity of coronary artery disease (CAD) in end-stage renal disease (ESRD) patients with dialysis.

Methods

A total of 408 ESRD patients with dialysis between January 2010 and December 2020 were enrolled including 204 patients diagnosed with CAD undergoing coronary angiography for the first time, and baseline characteristics as well as Gensini score (GS) were collected. Logistic regression analysis and linear regression analysis were performed to evaluate the relation of ABO blood types to the risk and severity of CAD, respectively.

Results

Blood group O frequency was significantly low in dialysis ESRD patients with CAD (25 vs. 38.24%) compared with the non-CAD patients and multivariable logistic regression showed blood group O was negatively associated with the risk of CAD [adjusted odds ratio (OR) = 0.33, 95% CI = 0.19–0.60, p < 0.001] as well as the GS tertiles (adjusted OR = 0.23, 95% CI = 0.11–0.49, p < 0.001) compared with A blood group. Blood group A, B, and AB were positively associated with the high Gensini tertile compared with O blood group (adjusted OR = 4.26, 95% CI = 2.03–8.93, p < 0.001; adjusted OR = 2.39, 95% CI = 1.11–5.13, p < 0.05; adjusted OR = 4.33, 95% CI = 1.40–13.35, P < 0.05). Similarly, multivariable linear regression results revealed O blood type was negatively associated with the GS (β = −26.129, 95% CI = −40.094 to −12.164, p < 0.001).

Conclusion

This case-control study demonstrated that blood group O was a potential independent protective factor for the risk and severity of CAD in ESRD patients with dialysis.
Outcomes of Different Ablation Approaches for Para-Hisian Accessory Pathway and Ablation Safety at Each Site
Authors: Yang Jian-du , Sun Qi , Guo Xiao-gang , Zhou Gong-bu , Liu Xu , Wei Hui-qiang , Xie Hai-yang , Ma Jian
Published: January 2022

Background

This study describes the electrophysiologic characteristics of the para-hisian accessory pathway (AP), the outcome of different ablation approaches, and ablation safety at different sites.

Method

A total of 120 patients diagnosed as para-hisian AP were included in this study. The electrophysiologic characteristics and outcomes at different ablation sites were analyzed.

Results

In total, 107 APs and 13 APs were diagnosed as right anteroseptal (RAS) and right midseptal (RMS), respectively. The significant ECG difference between RAS and RMS was lead III, which mainly manifested as positive and negative delta waves, respectively. Catheter trauma to AP was recorded in 21 of 120 (17.5%) patients. The recurrence rate of direct ablation at the “bumped” sites was higher than the conventional ablation method (37.5 vs. 14.1 %, p = 0.036). For RAS APs, there was no significant difference in the success rate between the inferior vena cava (IVC) and superior vena cava (SVC) approaches (76.6 vs. 73.3%, p = 0.63). The RAS was separated into three regions: (1) Site 1: superior part above the real “His” recorded site with far-field “His” potential; (2) Site 2 (true para-hisian): the site with near-field “His” potential; and (3) Site 3: inferior part below the biggest real “His” with far-field “His” potential. Mid-septal was defined as an area that is bounded anteriorly by His recording location and posteriorly by the roof of coronary sinus (CS) ostium. The incidence of atrioventricular (AV) conduction injury at different sites was as follows: 3 of 6 (50%) at Site 2, 4 of 13 (30.8%) at RMS, 7 of 34 (20.6%) at Site 3, and 3 of 46 (6.5%) at Site 1. Even if ablation was performed at the atrial side of the para-hisian region, the right bundle branch block (RBBB) was caused in 6 patients (5%).

Conclusion

Ablation via IVC or SVC was comparative for para-hisian APs, but not for the noncoronary cusp (NCC) approach. The AV conduction injury risk ranks as follows: Site 2 > RMS > Site 3 > Site 1. RBBB could be caused while ablating at the atrial side, which could further demonstrate the His bundle longitudinal dissociation theory.
Multimorbidity and Polypharmacy in Chinese Emergency Department Patients With Atrial Fibrillation and Impacts on Clinical Outcomes
Authors: Wang Juan , Yang Yan-min , Zhu Jun , Zhang Han , Shao Xing-hui
Published: January 2022

Background and Objects

Few studies focus on multimorbidity and polypharmacy in Chinese atrial fibrillation (AF) patients. We examined the impact of multimorbidity, polypharmacy, and treatment strategies on outcomes in Chinese emergency department (ED)AF patients. We also assessed factors associated with vitamin K antagonist (VKA) non-use in AF patients with multimorbidity or polypharmacy.

Methods

2015 AF patients who presented to emergency department (ED) were enrolled from Nov 2008 to Oct 2011, mean follow-up of 12-months. Cox regressions were performed to identify the impact of multimorbidity and polypharmacy on clinical outcomes.

Results

Six hundred and sixty-five patients in low morbidity group (≤1 comorbidity), 608 patients in moderate morbidity group (2 comorbidities), 742 patients in high morbidity group (≥3 comorbidities). Five hundred and seventy patients (28.3%) had polypharmacy (≥5 medications). High and moderate morbidity groups were significantly associated with a higher risk of all-cause death (HR 2.083, 95%CI 1.482–2.929; HR 1.713, 95%CI 1.198–2.449), CV death (HR 2.457, 95%CI 1.526–3.954; HR 1.974, 95%CI 1.206–3.232) and major bleeding (HR 4.126, 95%CI 1.022–16.664; HR 6.142, 95%CI 1.6789–22.369) compared with low morbidity group. In VKA subgroup, only high morbidity group was associated with a higher risk of all-cause death (HR 2.521, 95%CI 1.482–2.929), but not significantly in other events. For polypharmacy category, there were no significant statistics among these endpoints. Coronary artery disease (CAD), hypertension, chronic obstructive pulmonary disease, and antiplatelet therapy were independent predictors for VKA non-use in whole cohort, and patients with multimorbidity. CAD and antiplatelet therapy were independent predictors for VKA non-use in patients with polypharmacy.

Conclusion

Multimorbidity was associated with worse outcomes in Chinese ED AF patients. Polypharmacy showed no significant statistics among these outcomes. CAD and antiplatelet therapy were independent risk factors of VKA non-use in Chinese ED AF patients with multimorbidity or polypharmacy.
Association of Central Obesity With All Cause and Cause-Specific Mortality in US Adults: A Prospective Cohort Study
Authors: Huai Pengcheng , Liu Jian , Ye Xing , Li Wen-Qing
Published: January 2022

Background

Previous data on the association between central obesity and mortality are controversial. The aim of this study was to determine the associations between central obesity, as measured by the waist-to-height ratio (WtHR) and waist circumference (WC), with all cause and cause-specific mortality in U.S. adults.

Methods

The study subjects comprised a nationally representative sample of 33,569 adults >20 years of age who were recruited in the National Health and Nutrition Examination Survey between 1999 and 2014. Anthropometric data, including weight, height, and WC, were measured at each of the eight waves using consistent methodology. Death and underlying causes of death were ascertained through 31 December 2015. The association between central obesity and mortality were determined using weighted Cox proportional hazards regression models.

Results

A total of 4013 deaths occurred during a median follow-up of 7.33 years (263,029 person-years). Compared with the subjects in WtHR tertile 1, the subjects in tertiles 2 and 3 were at a higher risk of mortality from all-cause (tertile 2-hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.13–1.47; tertile 3-HR: 1.96; 95% CI: 1.64–2.34) and cardiovascular diseases [CVDs] (tertile 2-HR: 1.40; 95% CI: 1.09–1.79; tertile 3-HR: 2.00; 95% CI: 1.47–2.73). Similarly, compared with the subjects in WC tertile 1, the subjects in tertiles 2 and 3 were at a higher risk of mortality from all-cause (tertile 2-HR: 1.15; 95% CI: 1.00–1.31; tertile 3-HR: 1.39; 95% CI: 1.15–1.67) and CVD (tertile 2-HR: 1.48; 95% CI: 1.14–1.93; tertile 3-HR: 1.74; 95% CI: 1.26–2.42). Restricted cubic spline analyses revealed an S-shaped and linear dose-relationship between WtHR and WC with all-cause mortality. Moreover, a WtHR> 0.58 or a WC > 0.98m was shown to be a risk factor for all-cause mortality.

Conclusions

Central obesity was significantly associated with increased risk of all-cause and CVD-related mortality, especially heart diseases-related mortality, even among normal weight adults. In addition to weight control, guideline designer should provide recommendations for people to decrease abdominal fat accumulation, in their effort to reduce mortality risk in later life.
Relationship Between Dental Caries and Erosive Tooth Wear in Adolescents
Authors: Weber Megan L. , Søvik Jenny Bogstad , Mulic Aida , Deeley Kathleen , Modesto Adriana , Tveit Anne B. , Vieira Alexandre R.
Published: January 2022

Background

Our aim was to investigate the relationship between caries experience and erosive tooth wear in adolescents.

Methods

We compared the Decayed, Missing, and Filled Teeth (dmft/DMFT) data of 795 adolescents to their erosive tooth wear scores using diet as a covariate and determined whether dental caries and erosive tooth wear scores are associated with each other, using linear regression analysis. Diet data and oral hygiene habits were collected using self-reported surveys and erosive tooth wear scores were previously collected. We also compared patients' genotypes and phenotypes and looked for an association between erosive tooth wear experience and different single nucleotide polymorphisms (SNPs). A Bonferroni correction was implemented to correct multiple comparisons. Two-group comparisons were made depending on the phenotype definitions implemented, and both chi-square and linear regression analyses were used to the test association between genetic variants and caries definitions. All covariates were included in each model.

Results

For four SNPs (rs17159702, rs10246939, rs1800972, and rs1676303), there was an association between a spike in caries experience of DMFT 4 or more between two time points and increased frequency of fruit juice intake. A fifth SNP rs2860216 was shown to be a protective factor against a caries spike when associated with more frequent yogurt consumption. We did not find significant associations between our dental caries phenotypes or our demographic data and erosive tooth wear status in our linear regression.

Conclusions

Dental caries and erosive tooth wear are two diseases that differ in mechanism and heritability.
Cognitive and Linguistic Effects of Working Memory Training in Children With Corresponding Deficits
Authors: Pauls Laura J. , Archibald Lisa M. D.
Published: January 2022

Working memory training has been found to result in improvements on tasks similar to those involved in the training (near transfer) but show limited impact on everyday skills such as language or academic abilities (far transfer). Previous research has largely focused on those with a broad range of skills, and examined group level responses. This study uses a single subject design to examine the effect of working memory training on both working memory and related domains in children with working memory impairment. Seven children (8–11 years old) with a working memory impairment completed 20 sessions of computerized working memory intervention. Data revealed near transfer for all participants. Evidence of far transfer to improvements in language, reading, or math was observed for approximately half of the participants on individual measures. Three participants showed convincing but modest training effects across multiple measures. A combination of factors appeared to influence far transfer including age, training intensity, and baseline measures.
The Effects of Flipped Learning on Learning and Motivation of Upper Secondary School Physical Education Students
Authors: Ferriz-Valero Alberto , Østerlie Ove , Penichet-Tomas Alfonso , Baena-Morales Salvador
Published: January 2022

New technologies are increasingly linked to the educational world. It is necessary to develop pedagogical approaches such as flipped learning so that education and technology improve the quality of teaching to contribute to quality and sustainable education. Over the years this pedagogical approach has developed quite a bit; however, the scientific literature in physical education is still limited. The objective of the present study was to quantitatively evaluate the effects of the application of flipped learning in the acquisition of the conceptual contents of sport, in the case of the present study through volleyball. A total of 265 upper secondary school students participated in the study (126 boys: 47.9% and 137 girls: 52.1%). The total sample set was divided into two treatment groups. The first experimental treatment group received lessons with the support of flipped learning, through the Edpuzzle platform. The second treatment group or control group received the same content as the first group through traditional methodology. The findings showed that upper secondary students benefited from flipped learning in their cognitive learning about volleyball in physical education, compared to the control group. Further, the findings showed the same results on motivation, although certain differences appeared according to sex, where boys seemed to develop autonomous motivation more than girls.
G Protein-Coupled Receptors in Osteoarthritis
Authors: Wang Fanhua , Liu Mingyao , Wang Ning , Luo Jian
Published: January 2022

Osteoarthritis (OA) is the most common chronic joint disease characterized, for which there are no available therapies being able to modify the progression of OA and prevent long-term disability. Critical roles of G-protein coupled receptors (GPCRs) have been established in OA cartilage degeneration, subchondral bone sclerosis and chronic pain. In this review, we describe the pathophysiological processes targeted by GPCRs in OA, along with related preclinical model and/or clinical trial data. We review examples of GPCRs which may offer attractive therapeutic strategies for OA, including receptors for cannabinoids, hormones, prostaglandins, fatty acids, adenosines, chemokines, and discuss the main challenges for developing these therapies.
Implementation of Islanding Recognizing Technique for Wind Distributed Generations Considering Insignificant NDZ
Authors: Raza Safdar , Munir Hafiz Mudassir , Shafique Nouman , Amjad Wajiha , Bajaj Mohit , Alghaythi Mamdouh L.
Published: January 2022

The incorporation of distributed energy resources (DERs) into the electricity grid yields environmental, technical, and economic benefits. However, in addition to the benefits, the widespread use of DERs causes technical issues. Islanding is a big concern in terms of equipment protection and personnel safety, and it should be detected as soon as possible. The proposed approach employs a passive islanding detection technique based on reactive power (Q). The Q was chosen following a comparison of five other indices. Comparative analysis reveals that Q has the highest sensitivity and accuracy for islanding recognition when compared to all other observed parameters. Different case studies have been performed considering the worst-case scenario to check the working efficiency of the proposed scheme that simply distinguishes the islanding conditions from non-islanding conditions, which include load, motor, and capacitor switching, various types of fault switching, DG tripping cases, and weak grid contribution. The proposed strategy is straightforward, with quick execution and simple implementation in the MATLAB/SIMULINK environment on the IEEE 1547-2018 generic test system. With a small non-detection zone, islanding is detected in 0.038 s.
Various Green Nanomaterials Used for Wastewater and Soil Treatment: A Mini-Review
Authors: Nakum Jayraj , Bhattacharya Debleena
Published: January 2022

The industrial intervention had a profound impact on our environment and the amount of damage it has bestowed is in the form of polluted water and solid waste accumulation. With upgradation of technologies in the industrial upfront there is also an increase in the robust nature of industrial waste. Keeping in view of the various environmental aspects, advanced techniques were developed by the inculcation of nanotechnology. Among the diverse technologies that have gained prominence is the use of nanoparticles as a medium to monitor and treatment process. One of them is the use of organic techniques, i.e., the use of nano-chitosan. The review article focuses on the new data pertaining to the study and improvement of various nano-scale treatment technologies implemented for wastewater treatment with an environment friendly biodegradation. The eradication of harmful toxicants is an exhaustive process, but this is required to invigorate the sustainable development. Various strategies were promulgated but the inculcation of nanomaterial provided a low-cost, efficient and simple method for removal of contaminants by adsorption. These nanomaterials provide the best adsorbent due to its simple structural properties that provide a better surface area with high absorption capacity. This comprehensive review gives a glimpse of the various green and other nanotechnologies used for wastewater and contaminated soil treatments.
A Glycosylphosphatidylinositol-Anchored α-Amylase Encoded by amyD Contributes to a Decrease in the Molecular Mass of Cell Wall α-1,3-Glucan in Aspergillus nidulans
Authors: Miyazawa Ken , Yamashita Takaaki , Takeuchi Ayumu , Kamachi Yuka , Yoshimi Akira , Tashiro Yuto , Koizumi Ami , Ogata Makoto , Yano Shigekazu , Kasahara Shin , Sano Motoaki , Yamagata Youhei , Nakajima Tasuku , Abe Keietsu
Published: January 2022

α-1,3-Glucan is one of the main polysaccharides in the cell wall of Aspergillus nidulans. We previously revealed that it plays a role in hyphal aggregation in liquid culture, and that its molecular mass (MM) in an agsA-overexpressing (agsAOE) strain was larger than that in an agsB-overexpressing (agsBOE) strain. The mechanism that regulates its MM is poorly understood. Although the gene amyD, which encodes glycosylphosphatidylinositol (GPI)-anchored α-amylase (AmyD), is involved in the biosynthesis of α-1,3-glucan in A. nidulans, how it regulates this biosynthesis remains unclear. Here we constructed strains with disrupted amyD (ΔamyD) or overexpressed amyD (amyDOE) in the genetic background of the ABPU1 (wild-type), agsAOE, or agsBOE strain, and characterized the chemical structure of α-1,3-glucans in the cell wall of each strain, focusing on their MM. The MM of α-1,3-glucan from the agsBOEamyDOE strain was smaller than that in the parental agsBOE strain. In addition, the MM of α-1,3-glucan from the agsAOE ΔamyD strain was greater than that in the agsAOE strain. These results suggest that AmyD is involved in decreasing the MM of α-1,3-glucan. We also found that the C-terminal GPI-anchoring region is important for these functions.
Utilization of CRISPR-Mediated Tools for Studying Functional Genomics in Hematological Malignancies: An Overview on the Current Perspectives, Challenges, and Clinical Implications
Authors: Solayappan Maheswaran , Azlan Adam , Khor Kang Zi , Yik Mot Yee , Khan Matiullah , Yusoff Narazah Mohd , Moses Emmanuel Jairaj
Published: January 2022

Hematological malignancies (HM) are a group of neoplastic diseases that are usually heterogenous in nature due to the complex underlying genetic aberrations in which collaborating mutations enable cells to evade checkpoints that normally safeguard it against DNA damage and other disruptions of healthy cell growth. Research regarding chromosomal structural rearrangements and alterations, gene mutations, and functionality are currently being carried out to understand the genomics of these abnormalities. It is also becoming more evident that cross talk between the functional changes in transcription and proteins gives the characteristics of the disease although specific mutations may induce unique phenotypes. Functional genomics is vital in this aspect as it measures the complete genetic change in cancerous cells and seeks to integrate the dynamic changes in these networks to elucidate various cancer phenotypes. The advent of CRISPR technology has indeed provided a superfluity of benefits to mankind, as this versatile technology enables DNA editing in the genome. The CRISPR-Cas9 system is a precise genome editing tool, and it has revolutionized methodologies in the field of hematology. Currently, there are various CRISPR systems that are used to perform robust site-specific gene editing to study HM. Furthermore, experimental approaches that are based on CRISPR technology have created promising tools for developing effective hematological therapeutics. Therefore, this review will focus on diverse applications of CRISPR-based gene-editing tools in HM and its potential future trajectory. Collectively, this review will demonstrate the key roles of different CRISPR systems that are being used in HM, and the literature will be a representation of a critical step toward further understanding the biology of HM and the development of potential therapeutic approaches.
Characterization of Chromosomal Instability in Glioblastoma
Authors: Balzano Elisa , Di Tommaso Elena , Antoccia Antonio , Pelliccia Franca , Giunta Simona
Published: January 2022

Glioblastoma multiforme (GBM) is a malignant tumor of the central nervous system (CNS). The poor prognosis of GBM due to resistance to therapy has been associated with high chromosomal instability (CIN). Replication stress is a major cause of CIN that manifests as chromosome rearrangements, fragility, and breaks, including those cytologically expressed within specific chromosome regions named common fragile sites (CFSs). In this work, we characterized the expression of human CFSs in the glioblastoma U-251 MG cell line upon treatment with the inhibitor of DNA polymerase alpha aphidicolin (APH). We observed 52 gaps/breaks located within previously characterized CFSs. We found 17 to be CFSs in GBM cells upon treatment with APH, showing a frequency equal to at least 1% of the total gaps/breaks. We report that two CFSs localized to regions FRA2E (2p13/p12) and FRA2F (2q22) were only found in U-251 MG cells, but not lymphocytes or fibroblasts, after APH treatment. Notably, these glioblastoma-specific CFSs had a relatively high expression compared to the other CFSs with breakage frequency between ∼7 and 9%. Presence of long genes, incomplete replication, and delayed DNA synthesis during mitosis (MiDAS) after APH treatment suggest that an impaired replication process may contribute to this loci-specific fragility in U-251 MG cells. Altogether, our work offers a characterization of common fragile site expression in glioblastoma U-251 MG cells that may be further exploited for cytogenetic and clinical studies to advance our understanding of this incurable cancer.
Identification of Alternative Polyadenylation in Cyanidioschyzon merolae Through Long-Read Sequencing of mRNA
Authors: Schärfen Leonard , Zigackova Dagmar , Reimer Kirsten A. , Stark Martha R. , Slat Viktor A. , Francoeur Nancy J. , Wells Melissa L. , Zhou Lecong , Blackshear Perry J. , Neugebauer Karla M. , Rader Stephen D.
Published: January 2022

Alternative polyadenylation (APA) is widespread among metazoans and has been shown to have important impacts on mRNA stability and protein expression. Beyond a handful of well-studied organisms, however, its existence and consequences have not been well investigated. We therefore turned to the deep-branching red alga, Cyanidioschyzon merolae, to study the biology of polyadenylation in an organism highly diverged from humans and yeast. C. merolae is an acidothermophilic alga that lives in volcanic hot springs. It has a highly reduced genome (16.5 Mbp) and has lost all but 27 of its introns and much of its splicing machinery, suggesting that it has been under substantial pressure to simplify its RNA processing pathways. We used long-read sequencing to assess the key features of C. merolae mRNAs, including splicing status and polyadenylation cleavage site (PAS) usage. Splicing appears to be less efficient in C. merolae compared with yeast, flies, and mammalian cells. A high proportion of transcripts (63%) have at least two distinct PAS’s, and 34% appear to utilize three or more sites. The apparent polyadenylation signal UAAA is used in more than 90% of cases, in cells grown in both rich media or limiting nitrogen. Our documentation of APA for the first time in this non-model organism highlights its conservation and likely biological importance of this regulatory step in gene expression.
The Identification of Two RNA Modification Patterns and Tumor Microenvironment Infiltration Characterization of Lung Adenocarcinoma
Authors: He Wan , Lin Gengpeng , Pan Chaohu , Li Wenwen , Shen Jing , Liu Yangli , Li Hui , Wu Dongfang , Lin Xuejia
Published: January 2022

Background: RNA modification plays an important role in many diseases. A comprehensive study of tumor microenvironment (TME) characteristics mediated by RNA modification regulators will improve the understanding of TME immune regulation.

Methods: We selected 26 RNA modification “writers” of lung adenocarcinoma (LUAD) samples and performed unsupervised clustering analysis to explore RNA modification patterns in LUAD. Differentially expressed genes (DEGs) with RNA modification patterns were screened to develop a “writers” of RNA modification score (WM score) system. The infiltration ratio of TME cell subsets was analyzed by CIBERSORT.

Results: We identified two RNA modification modes showing different characteristics of overall survival (OS) and TME cell infiltration. According to WM score, LUAD patients were divided into a high-WM score group and a low-WM score group. High-scored patients had a poor prognosis and higher tumor mutation burden (TMB), they were more sensitive to four LUAD therapies (erlotinib, XA V939, gefitinib, and KU-55933) and more clinically responsive to PD-L1 treatment. Those with a low WM score showed higher stromal scores, ESTIMATE scores, and survival chance.

Conclusion: Our work revealed the potential role of RNA modification patterns in TME, genetic variation, targeted inhibitor therapy, and immunotherapy. Identifying RNA modification pattern of LUAD patients help understand the characteristics of TME and may promote the development of immunotherapy strategies.
Case Report: Primary Pleural Angiosarcoma in a Patient With Klippel-Trenaunay Syndrome
Authors: Xu Jing , Liu Mengyao , Yuan Hongtu , Liu Zengjun , Zhu Dongyuan
Published: January 2022

Klippel-Trenaunay syndrome (KTS) was demonstrated as a mosaic activating PIK3CA mutations related overgrowth syndrome. We present the first case of primary pleural angiosarcoma in a 17-year-old woman with a history of KTS. The combined targeted DNA and RNA sequencing revealed an activating mutation in PIK3CA in the tumor tissue. Our case suggested an association and perhaps a causal link between the two different PIK3CA-related genetic diseases.
Whole-Exome Sequencing Implicates Neuronal Calcium Channel with Familial Atrial Fibrillation
Authors: Vad Oliver Bundgaard , Yan Yannan , Denti Federico , Ahlberg Gustav , Refsgaard Lena , Bomholtz Sofia Hammami , Santos Joana Larupa , Rasmussen Simon , Haunsø Stig , Svendsen Jesper Hastrup , Christophersen Ingrid Elizabeth , Schmitt Nicole , Olesen Morten Salling , Bentzen Bo Hjorth
Published: January 2022

Background: Atrial Fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, responsible for considerable morbidity and mortality. The heterogenic and complex pathogenesis of AF remains poorly understood, which contributes to the current limitation in effective treatments. We aimed to identify rare genetic variants associated with AF in patients with familial AF.

Methods and results: We performed whole exome sequencing in a large family with familial AF and identified a rare variant in the gene CACNA1A c.5053G > A which co-segregated with AF. The gene encodes for the protein variants CaV2.1-V1686M, and is important in neuronal function. Functional characterization of the CACNA1A, using patch-clamp recordings on transiently transfected mammalian cells, revealed a modest loss-of-function of CaV2.1-V1686M.

Conclusion: We identified a rare loss-of-function variant associated with AF in a gene previously linked with neuronal function. The results allude to a novel link between dysfunction of an ion channel previously associated with neuronal functions and increased risk of developing AF.
How Much Do Side Effects Contribute to Discontinuation? A Longitudinal Study of IUD and Implant Users in Senegal
Authors: Chin-Quee Dawn , Diadhiou Mohamed , Eichleay Margaret , Youssef Ahmed , Chen Mario , Bernholc Alissa , Stanback John
Published: January 2022

Introduction

In Senegal, discontinuation due to sides effects of long-acting, reversible contraceptives (LARCs) is relatively low; 5% of new implant acceptors and 11% of new IUD acceptors stop using in their first year because of health or side effect concerns. This study investigated factors associated with LARC discontinuation in the first 12 months of use in Senegal and explored how LARC users cope with side effects.

Methods

This mixed-method study involved quantitative interviews at five time points with LARC acceptors recruited from three service channels between February 2018 and March 2019. Qualitative interviews were conducted in August 2018 with a subset of those who experienced side effects. Logistic regression models identified factors associated with discontinuation due to side effects and discontinuation for any reason. Twelve-month discontinuation rates due to side effects were also estimated using a cumulative incidence function (CIF) approach to account for time to discontinuation.

Results

In logistic models, method choice (IUD or implant) [OR = 3.15 (95% CI: 1.91–5.22)] and parity [OR = 0.81 (95% CI: 0.7–0.94)] were associated with discontinuation due to side effects; IUD users and women with fewer children were more likely to discontinue. Results for all-cause discontinuation were similar: method choice [OR = 2.39 (95% CI: 1.6–3.58)] and parity [OR = 0.86 (95% CI: 0.77–0.96)] were significant predictors. The 12-month side effect CIF discontinuation rate was 11.2% (95% CI: 7.9–15.0%) for IUDs and 4.9% (95% CI: 3.5–6.6%) for implants. Side effect experiences varied, but most women considered menstrual changes the least acceptable. No statistically significant differences across services channels were observed.

Conclusions

In this study in Senegal, the choice between implants and IUDs had a significant impact on continuation, and women with more children continued LARC methods longer, despite side effects.
Cytokine Release Syndrome in Cancer Patients Receiving Immune Checkpoint Inhibitors: A Case Series of 25 Patients and Review of the Literature
Authors: Tay Sen Hee , Toh Michelle Min Xuan , Thian Yee Liang , Vellayappan Balamurugan A. , Fairhurst Anna-Marie , Chan Yiong Huak , Aminkeng Folefac , Bharwani Lavina D. , Huang Yiqing , Mak Anselm , Wong Alvin Seng Cheong
Published: January 2022

Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of immunotherapy. Unlike other immune-related adverse events, CRS triggered by immune checkpoint inhibitors (ICIs) is not well described. The clinical characteristics and course of 25 patients with ICI-induced CRS from 2 tertiary hospitals were abstracted retrospectively from the medical records and analyzed. CRS events were confirmed by 2 independent reviewers and graded using the Lee et al. scale. The median duration of CRS was 15.0 days (Q1; Q3 6.3; 29.8) and 10 (40.0%) had multiple episodes of CRS flares. Comparing the clinical factors and biomarkers in Grades 1-2 and 3-5 CRS, we found that patients with Grades 3-5 CRS had following: (i) had longer time to fever onset [25.0 days (Q1; Q3 13.0; 136.5) vs. 3.0 days (Q1; Q3 0.0; 18.0), p=0.027]; (ii) more cardiovascular (p=0.002), neurologic (p=0.001), pulmonary (p=0.044) and rheumatic (p=0.037) involvement; (iii) lower platelet count (p=0.041) and higher urea (p=0.041) at presentation compared to patients with Grades 1-2 CRS. 7 patients (28.0%) with Grades 1-2 CRS were rechallenged using ICIs without event. 9 patients (36.0%) were treated with pulse methylprednisolone and 6 patients (24.0%) were treated with tocilizumab. Despite this, 3 patients (50%) who received tocilizumab had fatal (Grade 5) outcomes from ICI-induced CRS. Longer time to fever onset, lower platelet count and higher urea at presentation were associated with Grade 3-5 CRS. These parameters may be used to predict which patients are likely to develop severe CRS.
Inhibiting KDM6A Demethylase Represses Long Non-Coding RNA Hotairm1 Transcription in MDSC During Sepsis
Authors: Bah Isatou , Youssef Dima , Yao Zhi Q. , McCall Charles E. , El Gazzar Mohamed
Published: January 2022

Myeloid-derived suppressor cells (MDSCs) prolong sepsis by promoting immunosuppression. We reported that sepsis MDSC development requires long non-coding RNA Hotairm1 interactions with S100A9. Using a mouse model that simulates the immunobiology of sepsis, we find that histone demethylase KDM6A promotes Hotairm1 transcription by demethylating transcription repression H3K27me3 histone mark. We show that chemical targeting of KDM6A by GSK-J4 represses Hotairm1 transcription, which coincides with decreases in transcription activation H3K4me3 histone mark and transcription factor PU.1 binding to the Hotairm1 promoter. We further show that immunosuppressive IL-10 cytokine promotes KDM6A binding at the Hotairm1 promoter. IL-10 knockdown repletes H3K27me3 and reduces Hotairm1 transcription. GSK-J4 treatment also relocalizes nuclear S100A9 protein to the cytosol. To support translation to human sepsis, we demonstrate that inhibiting H3K27me3 demethylation by KDM6A ex vivo in MDSCs from patients with protracted sepsis decreases Hotairm1 transcription. These findings suggest that epigenetic targeting of MDSCs in human sepsis might resolve post-sepsis immunosuppression and improve sepsis survival.