bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental performance and emissions of additively manufactured high-temperature combustion chambers for micro-gas turbines
Authors: Adamou Adamos , Costall Aaron , Turner James W.G. , Jones Andy , Copeland Colin
Published: March 2022

To date, 59 countries, representing 54% of global greenhouse gas emissions have made pledges for net-zero emissions targets within this century. This will require cleaner and more efficient sources of energy which is driving research into small-scale engines and auxiliary power units for hybrid vehicles and stationary power generation. A suitable candidate for such applications is the micro gas turbine due to its high-power density, reliability and low emissions. Further development of such engines is required though due to their increasing parasitic energy losses relative to net power output as size decreases. Additive manufacturing offers the design freedom to not only increase efficiencies but to also reduce emissions when applied to the various components of micro gas turbines. This article reports the effects of several additive manufacturing (AM) enabled design features for micro gas turbine combustion chambers via experimental testing of full-scale parts. The main objective of the additively manufactured features is the reduction of exhaust emissions by improving the air-fuel mixture distribution and consequently ignition and combustion. Using additive manufacturing a novel conical radial swirl-stabilized tubular combustor with internal vane fuel injection was created as a baseline for the laboratory testing. Several other features, including augmented backside liner cooling surfaces, in-vane lattice structures for fuel mixing and upstream liner fuel injection rings were also generated to further the investigations into additively manufactured features and their effects on fuel mixing. Using multiple combinations of all these features, 10 geometries were generated and tested at a variety of operating conditions. Three inlet temperatures were tested (500°C, 600°C and 700°C) with varying fuel flow rates to investigate their operating limits at a constant inlet pressure of 4 bar absolute. Test results for the full range of equivalence ratios and operating conditions showed that the upstream liner fuel injection designs generated NOx, CO and THC emissions on par with the baseline but showed a reduction in the maximum and minimum operating ranges. This design, however, demonstrated the distinct advantage of being able to ignite at full air mass flow; this is not possible with the baseline designs and is also an added benefit to its main use which is the reduction of liner temperature. Overall, the test results underscore that designing combustion chambers for additive manufacturing can provide a myriad of benefits not only for micro gas turbines but also for other applications requiring high efficiency combustion chambers.
The effects of e-stories on preschoolers’ narrative comprehension, retelling and reading attitudes among poor and good comprehenders
Authors: Altun Dilek
Published: March 2022

Previous studies have presented discrepant findings of e-stories’ contribution to children’s narrative comprehension, which can be attributed to not only the variation of multimedia features among studies but also to learner and text features. The main goal of the present study was to expand understanding of the effect of e-stories on children’s narrative skills and reading attitudes for poor and good story comprehenders. A quasi-experimental factorial design was employed to explore the effect of book type and group level on children’s narrative skills and reading attitudes. The participating children were pre-readers. The printed version of The Red Winged Owl was read aloud to small groups of 4–5 children. Participants included 41 good and 40 poor comprehenders (age range 59–68 months) who were identified based on narrative comprehension scores. The experimental group was exposed to four e-stories on an iPad, while the control group listened to readings of the printed versions of the same storybooks. Data were collected by administering pre- and post-tests and the preschool reading attitudes scale and by asking narrative comprehension questions. Children’s retellings were audio-recorded. The findings revealed that (a) the poor and good comprehender groups had higher narrative comprehension in the short text e-story condition, (b) there was a significant interaction effect for the narrative comprehension of poor and good comprehenders in longer texts and (c) children’s post-reading attitude scores did not differ by group level.
The “Esperanto” of business... or how to be successful in life: A decolonial reading, using semiotics, of English language courses’ advertisements in Brazil
Authors: Hemais Marcus W. , Pessôa Luís Alexandre , Barros Denise F.
Published: March 2022

The present paper seeks to analyze, based on the decolonial perspective, how the epistemic and ontological elements of the coloniality of power that operates through the linguistic imperialism of English are made present in the hierarchies of knowledge in marketing. For this, we use the generative trajectory, a semiotic theoretical model of meaning, to analyze advertisements of a transnational online English language company operating in Brazil, which reinforces in its communications the importance of learning English as the only way to succeed in the business world and to overcome the backwardness of local culture and language. The semiotic analysis helped to analyze the manipulation path and strategies and the concretization of the narratives present in the communication made through the ads, unveiling epistemic and ontological elements that make up the coloniality of power and its association to English, which was, in turn, related to the hierarchies of knowledge in marketing.
Dementia and dignity of identity: A qualitative evidence synthesis
Authors: Cruise Cera E , Lashewicz Bonnie M
Published: March 2022

In the late stages of dementia, individuals rely on others for their wellbeing and this creates an ethical imperative for responsive dementia care. Through a qualitative evidence synthesis of literature on what constitutes responsive dementia care, we identified dignity of identity as a central theme. Dignity of identity is the status each of us holds in relation to others and reflects our past experiences and our aspirations for the future. We did a qualitative evidence synthesis of 10 qualitative studies conducted with a total of 149 research participants, 95 of whom had dementia, and 54 of whom were paid and family member caregivers to people with dementia. Using “new materialism disability studies” as our theoretical framework, we illustrate how environments, both material and discursive, shape the abilities of people with dementia in residential care settings (RSCs) to live well and we use our findings to point to ways forward in dignity of identity-enhancing dementia care practice. Echoing the literature, we observe that people with dementia have the virtual capacity to live with dignity of identity and illustrate how material conditions and discourse influence the transition of dignity of identity in people with dementia from a virtual capacity to an actual capacity and how demonstrated capacity in turn influences material conditions and discourse surrounding care for people with dementia in RSCs. We call for a greater acknowledgement within literature on dignity and dementia of structural barriers to dignity of identity-enhancing care. The COVID-19 pandemic has shown us the fatal consequences of insufficient material conditions in RCSs and we hope that on a societal level there is improvement to both the material conditions in RCSs as well as an improvement in discourse about those who live and work in RCSs.
How do factors of sociodemographic, health literacy and dementia experience influence carers’ knowledge of dementia?
Authors: Crawley Sophie , Moore Kirsten , Vickerstaff Victoria , Fisher Emily , Cooper Claudia , Sampson Elizabeth L
Published: March 2022

Background

Dementia is a life limiting disease following a progressive trajectory. As carers often become key decision makers, their knowledge of dementia will have health implications for the person living with dementia as well as carer’s psychological wellbeing.

Aim

To explore how sociodemographic factors, health literacy and dementia experience influence family carers knowledge about dementia.

Method

In this cross-sectional, mixed methods study, we interviewed 150 family carers and assessed their dementia knowledge using the Dementia Knowledge Assessment Scale (DKAS). Linear regression analyses were used to examine whether health literacy, previous experiences of dementia, support group attendance and sociodemographic characteristics predicted knowledge. Sixteen carers also completed qualitative interviews which explored unmet information needs. Transcripts and field notes were thematically analysed.

Results

Most participants were partners (47%) or adult children (48%) and cared for someone with severe (32%) or moderate (43%) dementia. Mean DKAS scores were 34.8/50 (SD = 7.0, range = 17–48) reflecting 8/25 incorrect answers. Backwards elimination regression found greater dementia knowledge was associated with greater health literacy for appraising information (coef 3.48, 95% CI (1.38, 5.58); p = 0.001) and more years of education (coef 0.39, 95% CI (0.12, 0.65); p = 0.004). Although not significant, knowledge was slightly lower in those who attended a support group, and a trend was found between ability to understand health information and knowledge. Only 39% accurately identified dementia as life shortening, indicating notable gaps in knowledge. Four qualitative themes were identified; arm yourself with information, ability to steer through information, other experience of dementia can be helpful and the importance of relationships with health care professionals.

Conclusions

In an information age, vast amounts of information are available, but this can bring difficulties. Carers with more years of education and higher health literacy knew more about dementia. Professionals should consider how carers with lower health literacy can be supported through provision of timely, relevant information.
Machine learning and complex compositional principles in architecture: Application of convolutional neural networks for generation of context-dependent spatial compositions
Authors: Dzieduszyński Tomasz
Published: March 2022

A substantial part of architectural and urban design involves processing of compositional interdependencies and contexts. This article attempts to isolate the problem of spatial composition from the broader category of synthetic image processing. The capacity of deep convolutional neural networks for recognition and utilization of complex compositional principles has been demonstrated and evaluated under three scenarios varying in scope and approach. The proposed method reaches 95.1%–98.5% efficiency in the generation of context-fitting spatial composition. The technique can be applied for the extraction of compositional principles from the architectural, urban, or artistic contexts and may facilitate the design-related decision making by complementing the required expert analysis.
Using Systematic Social Observations to Measure Crime Prevention through Environmental Design and Disorder: In-situ Observations, Photographs, and Google Street View Imagery
Authors: Sas Marlies , Snaphaan Thom , Pauwels Lieven J.R. , Ponnet Koen , Hardyns Wim
Published: March 2022

This study focuses on the use of systematic social observations (SSO) to measure crime prevention through environmental design (CPTED) and disorder. To improve knowledge about measurement issues in small area research, SSO is conducted by means of three different methods: in-situ, photographs, and Google Street View (GSV) imagery. By evaluating the methodological quality of the observation methods, the results of our study suggest that virtual SSO approaches have considerable promise for the reliable assessment of physical properties of small areas. We discuss challenges and provide avenues for future research to encourage the evolution of a more reliable approach to measure the physical environment.
Development and Validation of a Concise Prediction Scoring System for Asian Lung Cancer Patients with EGFR Mutation Before Treatment
Authors: An Wenting , Fan Wei , Zhong Feiyang , Wang Binchen , Wang Shan , Gan Tian , Tian Sufang , Liao Meiyan
Published: March 2022

Purpose We aimed to determine the epidermal growth factor receptor ( EGFR) genetic profile of lung cancer in Asians, and develop and validate a non-invasive prediction scoring system for EGFR mutation before treatment. Methods This was a single-center retrospective cohort study using data of patients with lung cancer who underwent EGFR detection (n = 1450) from December 2014 to October 2020. Independent predictors were filtered using univariate and multivariate logistic regression analyses. According to the weight of each factor, a prediction scoring system for EGFR mutation was constructed. The model was internally validated using bootstrapping techniques and temporally validated using prospectively collected data (n = 210) between November 2020 and June 2021.Results In 1450 patients with lung cancer, 723 single mutations and 51 compound mutations were observed in EGFR. Thirty-nine cases had two or more synchronous gene mutations. We developed a scoring system according to the independent clinical predictors and stratified patients into risk groups according to their scores: low-risk (score <4), moderate-risk (score 4-8), and high-risk (score >8) groups. The C-statistics of the scoring system model was 0.754 (95% CI 0.729-0.778). The factors in the validation group were introduced into the prediction model to test the predictive power of the model. The results showed that the C-statistics was 0.710 (95% CI 0.638-0.782). The Hosmer–Lemeshow goodness-of-fit showed that χ2 = 6.733, P = 0.566. Conclusions The scoring system constructed in our study may be a non-invasive tool to initially predict the EGFR mutation status for those who are not available for gene detection in clinical practice.
An intrusion detection mechanism for IPv6-based wireless sensor networks
Authors: Wei Min , Rong Chunmeng , Liang Erxiong , Zhuang Yuan
Published: March 2022

With the advancement of IPv6 technology, many nodes in wireless sensor networks realize seamless connections with the Internet via IPv6 addresses. Security issues are a significant obstacle to the widespread adoption of IPv6 technology. Resource-constrained IPv6 nodes face dual attacks: local and Internet-based. Moreover, constructing an active cyber defense system for IPv6-based wireless sensor networks is difficult. In this article, we propose a K-nearest neighbor-based intrusion detection mechanism and design a secure network framework. This mechanism trains an intrusion detection algorithm using a feature data set to create a normal profile. The intrusion detection algorithm uses the normal profile to perform real-time detection of network traffic data to achieve rapid detections connecting many devices in a wireless sensor network. In addition, we develop a test platform to verify this mechanism. Experimental results show that this mechanism is appropriate for IPv6-based wireless sensor networks and achieves a low false-positive rate and good intrusion detection accuracy at an acceptable resource cost.
Exploring the vulnerability in the inference phase of advanced persistent threats
Authors: Wu Qi , Li Qiang , Guo Dong , Meng Xiangyu
Published: March 2022

In recent years, the Internet of Things has been widely used in modern life. Advanced persistent threats are long-term network attacks on specific targets with attackers using advanced attack methods. The Internet of Things targets have also been threatened by advanced persistent threats with the widespread application of Internet of Things. The Internet of Things device such as sensors is weaker than host in security. In the field of advanced persistent threat detection, most works used machine learning methods whether host-based detection or network-based detection. However, models using machine learning methods lack robustness because it can be attacked easily by adversarial examples. In this article, we summarize the characteristics of advanced persistent threats traffic and propose the algorithm to make adversarial examples for the advanced persistent threat detection model. We first train advanced persistent threat detection models using different machine learning methods, among which the highest F1-score is 0.9791. Then, we use the algorithm proposed to grey-box attack one of models and the detection success rate of the model drop from 98.52% to 1.47%. We prove that advanced persistent threats adversarial examples are transitive and we successfully black-box attack other models according to this. The detection success rate of the attacked model with the best attacked effect dropped from 98.66% to 0.13%.
The quantitative detection of botanical trashes contained in seed cotton with near infrared spectroscopy method
Authors: Zhou Wanhuai , Li Hao , Liang Houjun
Published: March 2022

This study is performed to investigate the potential of near infrared (NIR) spectroscopy for the detection of botanical trashes content of seed cotton harvested by cotton-picker (SCHCP). Large quantity of trashes become comingled with cotton fiber in the harvesting process, especially when the cotton is harvested with cotton-picker. In China, trashes content of seed cotton (SC) has to be detected when farmers sell the SC to ginneries because trashes reduce the prices of SC and it should be deducted from the whole weight. The conventional instrumental method used to detect the trashes content of SC, ginning and trashes analysis, is complex and time consuming. In this study, 353 SC samples were collected from three ginneries, the NIR spectra bands from 12,000 to 4000 cm−1 were collected with the FT-NIR spectrometer Nexus. Models between NIR spectra and the trashes contents of these SC samples have been developed with the method of partial least square regression (PLSR), bands of 12,000–4000 cm−1, multiplicative signal correction (MSC) was used to eliminate the negative effects caused by sample shapes, second derivative spectra were used to eliminate the translation and the rotation in the spectral baseline. And the parameters of optimized model: R2 is up to 0.985 (calibration set) and 0.973 (prediction set), RMSEC is as low as 0.072 g and RMSEP is 0.158 g. Results of ANOVA also certified the trashes contents calculated with the models are consistent with the actual trashes contents.
Dosing of Health and Wellness Coaching for Obesity and Type 2 Diabetes: Research Synthesis to Derive Recommendations
Authors: Sforzo Gary A. , Kaye Miranda P. , Faber Aubrey , Moore Margaret
Published: March 2022

Health and wellness coaching (HWC) is an effective intervention for lifestyle disease such as obesity and type 2 diabetes. The evolving HWC profession needs recommendations to guide clinical practice, particularly the appropriate dose of coaching. The purpose of this paper was to systematically review and synthesize HWC literature to derive HWC programming recommendations. Of 102 papers retrieved, 88 were retained with data extracted determining HWC session number, frequency, duration, program length, and total coaching load. Differential analysis yielded no statistical difference in programming variables for randomized control trials and other designs, nor for studies with significant findings v. those not finding statistical significance, allowing these data to be pooled. The HWC intervention for obesity was slightly more intense (15 sessions over 7-8 mo) than the diabetes programming (12 sessions over 9-10 mo). On average, HWC programming applied in the peer-reviewed literature was 12-15 sessions of 35-40 min duration over 7-9 months. These recommendations for HWC programming variables are put forth as initial practice guidelines and should be examined with comparative effectiveness study for optimization. HWC best practice guidelines for other patient groups (e.g., heart disease, cancer, and chronic pain) should also be studied once an adequate literature data base is available.
Mixed convection and thermally radiative hybrid nanofluid flow over a curved surface
Authors: Gohar  , Saeed Khan Tahir , Khan Imran , Gul Taza , Bilal Muhammad
Published: March 2022

This study explored the Darcy Forchheimer flow of Casson hybrid nanofluid (NF) via a persistently stretching curved surface. The Darcy-Forchheimer contribution articulates viscous fluid flow in permeable media. Hybrid nanofluids are made from carbon nanotubes (CNTs) having a cylindrical shape and iron ferrite nanoparticulate. The main equations are reorganized into non-dimensional ODEs via similarity replacement. To accomplish the analytic simulation of modeled equations, the “Homotopy analysis approach” is performed. The effects of flow factors on velocity and energy profiles have been tabulated and discussed. It has been noticed that the integration of iron ferrite and CNT nanoparticulate in the base fluid to control the coolant level in industrial apparatus is quite useful. The energy field ascension effect is helpful for industrial uses since the energy fields exhibit favorable behavior against rising values of both type of nanomaterials. The Casson constraint’s rising values decline the hybrid NF motion.
Rolling bearing performance degradation evaluation using grey entropy
Authors: Cheng Li , Ma Wensuo , Xia Xintao , Wang Liangwen
Published: March 2022

Entropy-based nonlinear dynamic techniques have been considered to be a powerful tool and widely and successfully utilized to analyze the vibration signals in rolling bearing. This paper presents a new entropy-based nonlinear dynamic method, called the Grey entropy (GreyEn) for vibration performance degradation evaluation of rolling bearing. Similar to the existing measures, GreyEn is the negative natural logarithm of the conditional probability that two vectors similar for m points remain similar for the next m+1 points. Importing the concept of grey system theory, vectors’ similarity is measured by the grey relational degree (GRD). Simulation signals are employed to evaluate the effectiveness of the proposed method. The results suggest that GreyEn, compared with sample entropy (SampEn) and fuzzy entropy (FuzzyEn), leads to more efficiently measure the complexity. The validity of GreyEn is also assessed through three experimental tests. The experimental results show that GreyEn, compared with SampEn and FuzzyEn, can effectively evaluate the vibration performance degradation of the rolling bearing.
Accounting for the rarity of the disease when designing clinical trials with a focus on pediatric cancers
Authors: Mauguen Audrey
Published: March 2022

Background

Clinical trials are challenging in rare diseases like pediatric cancers, where the accrual is limited. In these trials, inference assumptions are the same as in common diseases, that is the sample comes from a quasi-infinite population. This leads to overestimating the variance of the mean treatment effect. The finite-population correction factor correcting this bias is often used in surveys, but not in clinical trials. With few assumptions, the use of this correction factor can improve trials efficiency, showing that the power of those trials is sometimes higher than it appears.

Methods

First, a simulation study assesses the standard error of the mean treatment effect and coverage of the 95% confidence interval with and without the correction. Second, the analytical power of a z-test with and without the correction is given. Finally, the impact on the sample size calculation is investigated. The impact of assuming a finite population is assessed for varying treatment effect, sample size and population size.

Results

The simulation results confirm the overestimation of the standard error without the correction factor. When using the correction factor, the gain in power reaches up to 10.1%, 15.3% and 12.3% to detect a difference in treatment effect of 10%, 15% and 20%, respectively. The gain is negligible for n = 30, in scenarios with high power (>95%), and for large populations. This gain in power translates into a decrease in sample size: if the conventional calculation leads to a sample size 10% of the population size, then the sample size can be divided by 1.1; if the conventional calculation leads to a sample size 20% of the population size, then the sample size can be divided by 1.2, in order to reach the planned type I error and power.

Conclusion

When dealing with rare diseases like pediatric cancers, the power of clinical trials might be higher than it appears if using conventional sample sizes. When correcting the variance of the mean using the population size, a gain in efficiency is observed with reasonable sample sizes and treatment differences for very small population sizes, showing that this approach can be useful for some pediatric cancer clinical trials.
Direct to angiography suite approaches for the triage of suspected acute stroke patients: a systematic review and meta-analysis
Authors: Brehm Alex , Tsogkas Ioannis , Ospel Johanna M. , Appenzeller-Herzog Christian , Aoki Junya , Kimura Kazumi , Pfaff Johannes A.R. , Möhlenbruch Markus A. , Requena Manuel , Ribo Marc J. , Sarraj Amrou , Spiotta Alejandro M. , Sporns Peter , Psychogios Marios-Nikos
Published: March 2022

Background:

Increasing evidence suggests improved time metrics leading to better clinical outcomes when stroke patients with suspected large vessel occlusion (LVO) are transferred directly to the angiography suite (DTAS) compared with cross-sectional imaging followed by transfer to the angiography suite. We performed a systematic review and meta-analysis on the efficacy and safety of DTAS approaches.

Methods:

We searched Embase, Medline, Scopus, and clinicaltrials.gov for studies comparing outcomes of DTAS and conventional triage. Eligible studies were assessed for risk of bias. We performed a random-effects meta-analysis on the differences of median door-to-groin and door-to-reperfusion times between intervention and control group. Secondary outcomes included good outcome at 90 days (modified Rankin Scale ⩽ 2) rate of symptomatic intracranial hemorrhage (sICH) and mortality within 90 days.

Results:

Eight studies (one randomized, one cluster-randomized trial and six observational studies) with 1938 patients were included. Door-to-groin and door-to-reperfusion times in the intervention group were on median 29.0 min [95% confidence interval (CI): 14.3–43.6; p < 0.001] and 32.1 min (95% CI: 15.1–49.1; p < 0.001) shorter compared with controls. Prespecified subgroup analyses for transfer ( n = 1753) and mothership patients ( n = 185) showed similar reductions of the door-to-groin and door-to-reperfusion times in response to the intervention. The odds of good outcome did not differ significantly between both groups but were numerically higher in the intervention group (odds ratio: 1.38, 95% CI: 0.97–1.95; p = 0.07). There was no significant difference for mortality and sICH between the groups.

Conclusion:

DTAS approaches for the triage of suspected LVO patients led to a significant reduction in door-to-groin and door-to-reperfusion times but an effect on functional outcome was not detected. The subgroup analysis showed similar results for transfer and mothership patients. Registration﻿: This study was registered in PROSPERO (CRD42020213621).
First-line immunotherapy or angiogenesis inhibitor plus chemotherapy for HER2-altered NSCLC: a retrospective real-world POLISH study
Authors: Yang Guangjian , Yang Yaning , Liu Runze , Li Weihua , Xu Haiyan , Hao Xuezhi , Li Junling , Xing Puyuan , Zhang Shuyang , Ai Xin , Xu Fei , Wang Yan
Published: March 2022

Background:

There have been no comprehensive large-scale studies that have evaluated the benefits of chemotherapy-based regimens in addressing HER2-altered advanced non-small-cell lung cancer (NSCLC) in a first-line setting. Data on HER2 alteration subtypes and concomitant alterations are also limited. Accordingly, our retrospective, real-world POLISH study assesses the efficacy of first-line chemotherapy alone (C) as well as combinations with immune checkpoint inhibitors (C + I) or angiogenesis inhibitors (C + A) for HER2-altered NSCLC; molecular features are also reported.

Methods:

HER2-altered NSCLC patients who received a first-line treatment between November 2015 and September 2021 were screened. Patients treated with C, C + I, or C + A were included in our final efficacy analysis. Progression-free survival (PFS) was compared between the subgroups. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to evaluate concomitant alterations.

Results:

A total of 293 patients were screened, with an identification of HER2 amplification and 37 distinct HER2 mutations, and 210 cases treated with C, C + I, or C + A were ultimately included. C + A achieved longer PFS than C (5.63 vs 4.03 months, hazard ratio: 0.64, 95% confidence interval [CI]: 0.46–0.88, p = 0.006). C + I did not improve median PFS compared to C + A or C (both p > 0.05), despite the programmed cell death ligand-1 (PD-L1) expression or tumor mutational burden. KEGG analysis revealed that concomitant upregulation of PI3 K/AKT pathway signaling was common in HER2-altered NSCLC.

Conclusion:

Chemotherapy plus angiogenesis inhibitors may yield a greater survival benefit than chemotherapy alone in a first-line setting for HER2-altered NSCLC, whereas an immune-based combination therapy may not be superior to a sole chemotherapy regimen. Activation of PI3 K/AKT signaling may mediate immunosuppression in HER2-altered NSCLC.
A Phenomenological Analysis of Rural Women’s Childbirth Preferences
Authors: Sultana Aneela , Zeeshan Mahwish , Anzak Sohima
Published: March 2022

Women’s agency and reproductive control directly bear their current pregnancy and future childbearing experiences. This study deals with knowledge construction in childbirth planning. The study is based on a phenomenological approach relying on in-depth interviews of sixty married women of childbearing age who have recently been through the birthing process. Cultural discourses provide an understanding of socio-familial context reinforcing traditional home birthing. Findings indicate that the desire for natural childbirth experience, apprehensions regarding obstetric interventions by medical doctors, emotional support, comfort and assistance provided by female relatives, traditional birth attendants, and their husbands’ preference add to their decision for home birthing. In addition, another determinant was the role of authoritative knowledge and shared experiences of older women that may deprive many young women of the chance to access maternal care in hospitals. The study suggests that rural women effectively utilize reproductive health care services in Pakistan.
Stevens-Johnson Syndrome and Stroke Related to Mycoplasma
Authors: Yadava Sanjay K. , Adhikari Soumya , ojha Niranjan , Zaidi Syed Hammad , Hanish Jain , Fazili Tasaduq
Published: March 2022

Mycoplasma pneumonia usually causes asymptomatic to mild respiratory tract infection. However, nonrespiratory manifestations are not rare with involvement of various organ including skin, cardiovascular, central nervous system. We are presenting a 43-year-old male who presented with diffuse rash, sever mucositis, confusion, and complicated by ischemic stroke; also, review of mycoplasma related stroke and Stevens-Johnson syndrome.
Giant Retinal Pigment Epithelium Tear Resulting in Neurosensory Retinal Detachment: An Atypical Case
Authors: Rana Harkaran S. , Cox Anthony R. , Biles Evan C. , Broderick Kevin
Published: March 2022

Purpose:

We report a rare case of neurosensory retinal detachment (RD) in the setting of a giant retinal pigment epithelium (RPE) tear.

Methods:

A 58-year-old man presented with a macula-involving RD in the left eye. Exam revealed a neurosensory detachment inferiorly and RPE abnormalities temporally. Optical coherence tomography showed a large RPE tear and detachment in the temporal macula contiguous with a neurosensory RD.

Results:

No clear etiology was identified and failure of conservative management led to vitrectomy with RD repair. Follow-up intravenous fluorescein angiography 3 months postoperatively showed a large RPE window defect.

Conclusions:

RPE tears are common; however, concomitant neurosensory RD is rare. A thorough workup to determine treatable causative factors is necessary; in the event of idiopathic diagnosis, close follow-up is necessary to determine the need for surgery. Pars plana vitrectomy, external drainage of subretinal fluid, endolaser, and 5000-centistoke silicone oil placement were successful in this patient.
Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19
Authors: Henderson Michael W. , Lima Franciele , Moraes Carla Roberta Peachazepi , Ilich Anton , Huber Stephany Cares , Barbosa Mayck Silva , Santos Irene , Palma Andre C. , Nunes Thyago Alves , Ulaf Raisa Gusso , Ribeiro Luciana Costa , Bernardes Ana Flavia , Bombassaro Bruna , Dertkigil Sergio San Juan , Moretti Maria Luiza , Strickland Sidney , Annichino-Bizzacchi Joyce M. , Orsi Fernanda Andrade , Mansour Eli , Velloso Licio A. , Key Nigel S. , De Paula Erich Vinicius
Published: March 2022

Coagulation activation is a prominent feature of severe acute respiratory syndrome coronavirus 2 (COVID-19) infection. Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. We therefore sought to assess activation of the contact system and intrinsic pathway in individuals with COVID-19 infection. Baseline plasma levels of protease:serpin complexes indicative of activation of the contact and intrinsic pathways were measured in samples from inpatients with COVID-19 and healthy individuals. Cleaved kininogen, a surrogate for bradykinin release, was measured by enzyme-linked immunosorbent assay, and extrinsic pathway activation was assessed by microvesicle tissue factor–mediated factor Xa (FXa; MVTF) generation. Samples were collected within 24 hours of COVID-19 diagnosis. Thirty patients with COVID-19 and 30 age- and sex-matched controls were enrolled. Contact system and intrinsic pathway activation in COVID-19 was demonstrated by increased plasma levels of FXIIa:C1 esterase inhibitor (C1), kallikrein:C1, FXIa:C1, FXIa:α1-antitrypsin, and FIXa:antithrombin (AT). MVTF levels were also increased in patients with COVID-19. Because FIXa:AT levels were associated with both contact/intrinsic pathway complexes and MVTF, activation of FIX likely occurs through both contact/intrinsic and extrinsic pathways. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically total length of hospitalization, length of intensive care unit stay, and extent of lung computed tomography changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes.
A double-blind randomised placebo-controlled trial investigating the effects of lesogaberan on the objective cough frequency and capsaicin-evoked coughs in patients with refractory chronic cough
Authors: Badri Huda , Gibbard Carmen , Denton Dimitra , Satia Imran , Al-Sheklly Bashar , Dockry Rachel J. , Holt Kimberley , McGuiness Kevin , Treadway Sam , Whorwell Peter , Houghton Lesley , Lee Augustine , Escott K. Jane , Lee Theresa , Wilkinson Greame , Holt Alison , Canning Brendan J. , Smith Jacky A.
Published: March 2022

Objective

Baclofen is a centrally acting γ-aminobutyric acid type B (GABAB) receptor agonist which reduces gastro-oesophageal reflux and suppresses the cough reflex; however, central nervous system side-effects limit its use. Lesogaberan is a novel peripherally acting GABABagonist, but its effects on refractory chronic cough are unknown.

Design

We performed a single-centre, placebo-controlled, double-blind randomised crossover study in patients with chronic cough, refractory to the treatment of underlying conditions. Patients were randomised to treatment with lesogaberan 120 mg modified release twice daily or matched placebo for 2 weeks and then crossed over to the alternative therapy after a 2-week washout. The primary end-point was 24-h cough frequency measured with an acoustic monitoring system. In addition, cough responses to capsaicin were measured, and gastro-oesophageal reflux assessed by 24-h pH/impedance at screening.

Results

22 patients were randomised to receive lesogaberan/placebo or placebo/lesogaberan (female (73%); mean±sdage 63.7±7.2 years; median (interquartile range) cough duration 10.5 (5.8–17.0) years; mean (95% CI) 45 (29–67) reflux events in 24 h; two patients had abnormal oesophageal acid exposure times). Although lesogaberan reduced cough counts by 26% over placebo, this did not reach statistical significance (p=0.12). However, lesogaberan did significantly improve cough responses to capsaicin (p=0.04) and the number of cough bouts (p=0.04) compared with placebo. Lesogaberan was well tolerated in this study.

Conclusions

Lesogaberan improved cough hypersensitivity and the number of bouts of coughing, but not coughs per hour. This implies a possible role for peripheral GABABreceptors in refractory chronic cough.
Potential anticancer properties and mechanisms of thymoquinone in osteosarcoma and bone metastasis
Authors: Homayoonfal Mina , Asemi Zatollah , Yousefi Bahman
Published: March 2022

Despite great advances, therapeutic approaches of osteosarcoma, the most prevalent class of preliminary pediatric bone tumors, as well as bone-related malignancies, continue to demonstrate insufficient adequacy. In recent years, a growing trend toward applying natural bioactive compounds, particularly phytochemicals, as novel agents for cancer treatment has been observed. Bioactive phytochemicals exert their anticancer features through two main ways: they induce cytotoxic effects against cancerous cells without having any detrimental impact on normal cell macromolecules such as DNA and enzymes, while at the same time combating the oncogenic signaling axis activated in tumor cells. Thymoquinone (TQ), the most abundant bioactive compound of Nigella sativa, has received considerable attention in cancer treatment owing to its distinctive properties, including apoptosis induction, cell cycle arrest, angiogenesis and metastasis inhibition, and reactive oxygen species (ROS) generation, along with inducing immune system responses and reducing side effects of traditional chemotherapeutic drugs. The present review is focused on the characteristics and mechanisms by which TQ exerts its cytotoxic effects on bone malignancies.
miR-152-3p impedes the malignant phenotypes of hepatocellular carcinoma by repressing roundabout guidance receptor 1
Authors: Yin Tao , Zhao Haonan
Published: March 2022

Background

miR-152-3p functions as a tumour suppressor in the progression of hepatic tumorigenesis. Herein, we further discussed the prognostic significance and immune infiltration of miR-152-3p and its potential gene target in hepatocellular carcinoma (HCC).

Methods

The Cancer Genome Atlas (TCGA), Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB), Human Protein Atlas (HPA) and Kaplan–Meier Plotter databases were used to evaluate miR-152-3p and roundabout guidance receptor 1 (ROBO1) expression, prognosis and immune infiltration. In vitro cell experiments, including cell proliferation and apoptosis, were evaluated using Cell Counting Kit 8 (CCK8) and terminal-deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) assays.

Results

Up-regulation of ROBO1 functioned as an oncogene associated with poor prognosis, immune cell enrichment and cell proliferation in HCC. ROBO1 was significantly positively correlated with the enrichment of multiple immune cells and their biomarkers. Enrichment of type-2 T-helper (Th2) cells is an unfavourable biomarker of HCC prognosis. GSEA revealed that ROBO1 correlated with apoptosis, mitosis and carcinogenic signalling pathways. Suppression of cell proliferation and the enhancement of cell apoptosis by miR-152-3p mimics were counteracted by overexpression of ROBO1 in HCC cells.

Conclusion

ROBO1 expression is positively correlated with multiple immune checkpoint molecules, suggesting that ROBO1 may be a potential drug target to enhance the potency of immunotherapy. The miR-152-3p/ROBO1 signalling axis contributes to malignant progression and provides a prospective immunotherapeutic target for HCC.
CASowary: CRISPR-Cas13 guide RNA predictor for transcript depletion
Authors: Krohannon Alexander , Srivastava Mansi , Rauch Simone , Srivastava Rajneesh , Dickinson Bryan C. , Janga Sarath Chandra
Published: March 2022

Background

Recent discovery of the gene editing system - CRISPR (Clustered Regularly Interspersed Short Palindromic Repeats) associated proteins (Cas), has resulted in its widespread use for improved understanding of a variety of biological systems. Cas13, a lesser studied Cas protein, has been repurposed to allow for efficient and precise editing of RNA molecules. The Cas13 system utilizes base complementarity between a crRNA/sgRNA (crispr RNA or single guide RNA) and a target RNA transcript, to preferentially bind to only the target transcript. Unlike targeting the upstream regulatory regions of protein coding genes on the genome, the transcriptome is significantly more redundant, leading to many transcripts having wide stretches of identical nucleotide sequences. Transcripts also exhibit complex three-dimensional structures and interact with an array of RBPs (RNA Binding Proteins), both of which may impact the effectiveness of transcript depletion of target sequences. However, our understanding of the features and corresponding methods which can predict whether a specific sgRNA will effectively knockdown a transcript is very limited.

Results

Here we present a novel machine learning and computational tool, CASowary, to predict the efficacy of a sgRNA. We used publicly available RNA knockdown data from Cas13 characterization experiments for 555 sgRNAs targeting the transcriptome in HEK293 cells, in conjunction with transcriptome-wide protein occupancy information. Our model utilizes a Decision Tree architecture with a set of 112 sequence and target availability features, to classify sgRNA efficacy into one of four classes, based upon expected level of target transcript knockdown. After accounting for noise in the training data set, the noise-normalized accuracy exceeds 70%. Additionally, highly effective sgRNA predictions have been experimentally validated using an independent RNA targeting Cas system – CIRTS, confirming the robustness and reproducibility of our model’s sgRNA predictions. Utilizing transcriptome wide protein occupancy map generated using POP-seq in HeLa cells against publicly available protein-RNA interaction map in Hek293 cells, we show that CASowary can predict high quality guides for numerous transcripts in a cell line specific manner.

Conclusions

Application of CASowary to whole transcriptomes should enable rapid deployment of CRISPR/Cas13 systems, facilitating the development of therapeutic interventions linked with aberrations in RNA regulatory processes.
Characterization of UDP-glycosyltransferase family members reveals how major flavonoid glycoside accumulates in the roots of Scutellaria baicalensis
Authors: Pei Tianlin , Yan Mengxiao , Li Tian , Li Xiaoqiang , Yin Yijia , Cui Mengying , Fang Yumin , Liu Jie , Kong Yu , Xu Ping , Zhao Qing
Published: March 2022

Background

Flavonoid glycosides extracted from roots of Scutellaria baicalensis exhibit strong pharmaceutical antitumor, antioxidative, anti-inflammatory, and antiviral activities. UDP glycosyltransferase (UGT) family members are responsible for the transfer of a glycosyl moiety from UDP sugars to a wide range of acceptor flavonoids. Baicalin is the major flavonoid glycoside found in S. baicalensis roots, and its aglycone baicalein is synthesized from a specially evolved pathway that has been elucidated. However, it is necessary to carry out a genome-wide study of genes involved in 7-O-glucuronidation, the final biosynthesis step of baicalin, which might elucidate the relationship between the enzymes and the metabolic accumulation patterns in this medicinal plant.

Results

We reported the phylogenetic analysis, tissue-specific expression, biochemical characterization and evolutionary analysis of glucosyltransferases (SbUGTs) and glucuronosyltransferases (SbUGATs) genes based on the recently released genome of S. baicalensis. A total of 124 UGTs were identified, and over one third of them were highly expressed in roots. In vitro enzyme assays showed that 6 SbUGTs could use UDP-glucose as a sugar donor and convert baicalein to oroxin A (baicalein 7-O-glucoside), while 4 SbUGATs used only UDP-glucuronic acid as the sugar donor and catalyzed baicalein to baicalin. SbUGAT4 and SbUGT2 are the most highly expressed SbUGAT and SbUGT genes in root tissues, respectively. Kinetic measurements revealed that SbUGAT4 had a lower Km value and higher Vmax/Km ratio to baicalein than those of SbUGT2. Furthermore, tandem duplication events were detected in SbUGTs and SbUGATs.

Conclusions

This study demonstrated that glucosylation and glucuronidation are two major glycosylated decorations in the roots of S. baicalensis. Higher expression level and affinity to substrate of SbUGAT4, and expansion of this gene family contribute high accumulation of baicalin in the root of S. baicalensis.
Genome-wide analysis of JAZ family genes expression patterns during fig (Ficus carica L.) fruit development and in response to hormone treatment
Authors: Song Miaoyu , Wang Haomiao , Ma Huiqin , Zheng Chuanlin
Published: March 2022

Background

Jasmonate-ZIM domain (JAZ) repressors negatively regulate signal transduction of jasmonates, which regulate plant development and immunity. However, no comprehensive analysis of the JAZ gene family members has been done in the common fig (Ficus carica L.) during fruit development and hormonal treatment.

Results

In this study, 10 non-redundant fig JAZ family genes (FcJAZs) distributed on 7 chromosomes were identified in the fig genome. Phylogenetic and structural analysis showed that FcJAZ genes can be grouped into 5 classes. All the classes contained relatively complete TIFY and Jas domains. Yeast two hybrid (Y2H) results showed that all FcJAZs proteins may interact with the identified transcription factor, FcMYC2. Tissue-specific expression analysis showed that FcJAZs were highly expressed in the female flowers and roots. Expression patterns of FcJAZs during the fruit development were analyzed by RNA-Seq and qRT-PCR. The findings showed that, most FcJAZs were significantly downregulated from stage 3 to 5 in the female flower, whereas downregulation of these genes was observed in the fruit peel from stage 4 to 5. Weighted-gene co-expression network analysis (WGCNA) showed the expression pattern of FcJAZs was correlated with hormone signal transduction and plant-pathogen interaction. Putative cis-elements analysis of FcJAZs and expression patterns of FcJAZs which respond to hormone treatments revealed that FcJAZs may regulate fig fruit development by modulating the effect of ethylene or gibberellin.

Conclusions

This study provides a comprehensive analysis of the FcJAZ family members and provides information on FcJAZs contributions and their role in regulating the common fig fruit development.