bluuebunny/crossref_metadata_2025 huggingface dataset:
Mobilizing Megaproject Narratives for External Stakeholders: A Study of Narrative Instruments and Processes
Authors: Ninan Johan , Sergeeva Natalya
Published: June 2022

Megaprojects combine multiple external stakeholders, and a common narrative is essential to drive the project among often conflicting objectives. Narratives help organize people toward an agenda and therefore have performative and strategic implications. In this research, we explore how narratives are mobilized through narrative instruments and processes using the case study of the High Speed Two (HS2) megaproject in the United Kingdom. We record the use of three instruments—stories, labels, and comparisons—that undergo four processes: repeating, endorsing, humorizing, and actioning. These instruments and processes enable megaprojects to mobilize a narrative that helps in managing external stakeholders.
What complete mitochondrial genomes tell us about the evolutionary history of the black soldier fly, Hermetia illucens
Authors: Guilliet J. , Baudouin G. , Pollet N. , Filée J.
Published: June 2022

Background

The Black Soldier Fly (BSF) Hermetia illucens is a cosmopolitan fly massively used by industrial companies to reduce biowaste and produce protein and fat for poultry and aquaculture feed. However, the natural history and the genetic diversity of the BSF are poorly known. Here, we present a comprehensive phylogeny and time tree based on a large dataset of complete mitochondrial genomes better to understand the evolution and timing of the BSF.

Results

In this study, we analyzed 677 CO1 sequences derived from samples found all over the five continents, leading us to discover 52 haplotypes, including ten major haplotypes. This worldwide cryptic genetic and genomic diversity is mirrored at a local scale in France, in which we found five major haplotypes sometimes in sympatry. Phylogenetic analyses of 60 complete mitochondrial genomes robustly resolved the phylogeny of the major BSF haplotypes. We estimate the separation events of the different haplotypes at more than 2 million years for the oldest branches characterizing the ancestral split between present North American lineages and the other highly diverse south-central American clades, possibly the following radiation beyond the isthmus of Panama northwards. Our data confirm that this North American lineage ultimately gave birth to almost all commercial BSF stocks that participated in the worldwide BSF dissemination through farm escapements.

Conclusions

Our data resolve the phylogenetic relationships between the major lineages and give insights into the BSF’s short and long-term evolution. Our results indicate that commercial BSF stock’s genetic and genomic diversity is very low. These results call for a better understanding of the genomic diversity of the BSF to unravel possible specific adaptations of the different lineages for industrial needs and to initiate the selection process.
Combined lifestyle factors on mortality among the elder population: evidence from a Chinese cohort study
Authors: Sun Changqing , Liu Huimin , Xu Fei , Qin Ying , Wang Panpan , Zhou Qianyu , Liu Dandan , Jia Shanqun , Zhang Qiang
Published: June 2022

Background

Numerous studies have suggested that lifestyle-related factors are associated with mortality, however limited evidence is available for the Chinese elder population.

Methods

The data of this study was obtained from the Chinese Longitudinal Health Survey (CLHLS) during 2008 − 2018, lifestyle-related factors including body mass index (BMI), smoking, drinking, consumption of vegetables and fruits, physical activity and sleep duration were included as dependent variables in the analysis. A lifestyle risk score was created using six unhealthy behaviors: smoking, drinking, unhealthy weight, physical inactivity, not eat vegetables or fruits and short or prolonged sleep. The Kaplan–Meier curves were used to illustrate the cumulative effect of lifestyle factors on mortality and cox regression models were conducted to estimate the combined effects of lifestyle-related factors on total mortality.

Results

The results illustrated that low BMI, smoking, no fruit eating, and no physical inactivity were risk factors for total mortality. KM curves showed significant cumulative effect of unhealthy lifestyle factors on mortality. Compared with participants without any unhealthy factors, the hazard ratio (HR) for participants with six unhealthy factors was 1.335 (1.015,1.757) for all-cause mortality.

Conclusions

This study demonstrated poor adherence to a healthy lifestyle may increase all-cause mortality and specific combinations of lifestyle related factors have different effects on mortality among Chinese elderly population.
Quality newborn care in East New Britain, Papua New Guinea: measuring early newborn care practices and identifying opportunities for improvement
Authors: Wilson Alyce N. , Melepia Pele , Suruka Rose , Hezeri Priscah , Kabiu Dukduk , Babona Delly , Wapi Pinip , Spotswood Naomi , Bohren Meghan A. , Vogel Joshua P. , Kelly-Hanku Angela , Morgan Alison , Beeson James G. , Morgan Christopher , Vallely Lisa M. , Waramin Edward J. , Scoullar Michelle J. L. , Homer Caroline S. E.
Published: June 2022

Background

Renewed attention and investment is needed to improve the quality of care during the early newborn period to address preventable newborn deaths and stillbirths in Papua New Guinea (PNG). We aimed to assess early newborn care practices and identify opportunities for improvement in one province (East New Britain) in PNG.

Methods

A mixed-methods study was undertaken in five rural health facilities in the province using a combination of facility audits, labour observations and qualitative interviews with women and maternity providers. Data collection took place between September 2019 and February 2020. Quantitative data were analysed descriptively, whilst qualitative data were analysed using content analysis. Data were triangulated by data source.

Results

Five facility audits, 30 labour observations (in four of the facilities), and interviews with 13 women and eight health providers were conducted to examine early newborn care practices. We found a perinatal mortality rate of 32.2 perinatal deaths per 1000 total births and several barriers to quality newborn care, including an insufficient workforce, critical infrastructure and utility constraints, and limited availability of essential newborn medicines and equipment. Most newborns received at least one essential newborn care practice in the first hour of life, such as immediate and thorough drying (97%).

Conclusions

We observed high rates of essential newborn care practices including immediate skin-to-skin and delayed cord clamping. We also identified multiple barriers to improving the quality of newborn care in East New Britain, PNG. These findings can inform the development of effective interventions to improve the quality of newborn care. Further, this study demonstrates that multi-faceted programs that include increased investment in the health workforce, education and training, and availability of essential equipment, medicines, and supplies are required to improve newborn outcomes.
Higher body mass index was associated with better prognosis in diabetic patients with stage II colorectal cancer
Authors: Liu Xiao-Yu , Kang Bing , Cheng Yu-Xi , Yuan Chao , Tao Wei , Zhang Bin , Wei Zheng-Qiang , Peng Dong
Published: June 2022

Purpose

The purpose of this study is to analyze the effect of body mass index (BMI) on patients with concurrent colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM).

Methods

Patients who underwent primary radical CRC surgery from Jan 2011 to Jan 2020 were retrospectively collected. The perioperative information, overall survival (OS) and disease-free survival (DFS) were compared between the higher BMI group and the lower BMI group.

Results

A total of 574 patients with concurrent CRC and T2DM were included in this study. The higher BMI group had higher portion of hypertension (p < 0.01) and coronary heart disease (CHD) (p < 0.01). Furthermore, the higher BMI group had better OS (p = 0.016) and DFS (p = 0.040) than the lower BMI group in stage II CRC. In multivariate analysis, age (OS: p = 0.002, HR = 2.016, 95% CI = 1.307–3.109/ DFS: p = 0.003, HR = 1.847, 95% CI = 1.230–2.772), TNM stage (OS: p < 0.01, HR = 1.667, 95% CI = 1.281–2.169/ DFS: p = 0.001, HR = 1.545, 95% CI = 1.207–1.977), overall complications (OS: p = 0.004, HR = 1.837, 95% CI = 1.218–2.880/ DFS: p = 0.006, HR = 1.783, 95% CI = 1.184–2.686) and major complications (OS: p = 0.005, HR = 2.819, 95% CI = 1.376–5.774/ DFS: p = 0.014, HR = 2.414, 95% CI = 1.196–4.870) were independent factors of OS and DFS. Moreover, BMI (p = 0.019, HR = 0.413, 95% CI = 0.197–0.864) was an independent factor of OS in stage II CRC.

Conclusion

Higher BMI was associated with better OS in diabetic patients with stage II CRC.
Ecologic study of influenza vaccination uptake and COVID-19 death rate in New York City
Authors: Moreland Ashley , Gillezeau Christina , Eugene Adriana , Alpert Naomi , Taioli Emanuela
Published: June 2022

Background

The aim of this ecological study was to assess the area-level relationship between cumulative death rate for COVID-19 and historic influenza vaccination uptake in the New York City population.

Methods

Predictors of COVID-19 death included self-reported influenza vaccination in 2017, as well as four CDC-defined risk factors of severe COVID-19 infection available at the ecological level, which were diabetes, asthma, BMI 30–100 (2 kg/m2) and hypertension, in addition to race and age (65 + years).

Results

After adjusting for potential confounders, for every one-unit increase in influenza vaccination uptake for each zip code area, the rate of COVID-19 deaths decreased by 5.17 per 100,000 residents (p < 0.0001).

Conclusions

Zip codes with a higher prevalence of influenza vaccination had lower rates of COVID-19 mortality, inciting the need to further explore the relationship between influenza vaccination uptake and COVID-19 mortality at the individual level.
eHealth usage among Chinese college students: qualitative findings
Authors: LIU Hua-xuan , CHOW Bik-chu , HU Chun , HASSEL Holger , HUANG Wendy Yajun
Published: June 2022

Background

The information technology has developed rapidly with the evolution of internet environment transformed from requiring computer skills for information searching to self-managing health data and applying information. Therefore, a more diverse range of eHealth skills is required and these skills are referred as eHealth literacy. However, most eHealth literacy studies focused mainly on information searching skills. Little is known about eHealth usage behaviors of college students in this day and age.

Objectives

This study aimed to investigate how Chinese college students engage with eHealth tools and to determine the elements of their eHealth literacy.

Methods

A purposive sample of 18 Chinese college students was recruited for in-depth interviews. Interviewees included three males and three females of each city (Beijing, Wuhan and Putian) from sports, medical, and non-health-related majors. Conventional content analysis was applied for data analysis.

Results

The eHealth usage of different-major-students were compared and profiled by three themes of Expectance, Usage pattern and Perception. In Expectances, non-health major students applied eHealth only for urgent health need, sport major students used it to monitor health while medical major students, as frequent users for searching health database. In Usage pattern, purposes of eHealth for personal, practical and theoretical were identified for non-health major, sport major and medical major groups, respectively. In Perceptions, sport students felt more curious about eHealth than the other groups who perceived either fear (non-health students) or skeptical (medical students). By compiling those themes, the whole picture of eHealth usage was emerged. Based on that, the current study identified the related skills using the trilogy of Web 1.0 to 3.0, and derived a conceptual framework for eHealth literacy in the present day.

Conclusions

The current study obtained a comprehensive understanding of eHealth usage and a framework of eHealth literacy required for Chinese college students. And it gives a clearer look at web 3.0 related eHealth behaviors.
Ultrashort time-to-echo T2* and T2* relaxometry for evaluation of lumbar disc degeneration: a comparative study
Authors: Wu Li-Lan , Liu Li-Heng , Rao Sheng-Xiang , Wu Pu-Yeh , Zhou Jian-Jun
Published: June 2022

Background

To compare potential of ultrashort time-to-echo (UTE) T2* mapping and T2* values from T2*-weighted imaging for assessing lumbar intervertebral disc degeneration (IVDD),with Pfirrmann grading as a reference standard.

Methods

UTE-T2* and T2* values of 366 lumbar discs (L1/2-L5/S1) in 76 subjects were measured in 3 segmented regions: anterior annulus fibrosus, nucleus pulposus (NP), and posterior annulus fibrosus. Lumbar intervertebral discs were divided into 3 categories based on 5-level Pfirrmann grading: normal (Pfirrmann grade I),early disc degeneration (Pfirrmann grades II-III), and advanced disc degeneration (Pfirrmann grades IV-V). Regional differences between UTE-T2* and T2* relaxometry and correlation with degeneration were statistically analyzed.

Results

UTE-T2* and T2*value correlated negatively with Pfirrmann grades (P < 0.001). In NP, correlations with Pfirrmann grade were high with UTE-T2* values (r =  − 0.733; P < 0.001) and moderate with T2* values (r = -0.654; P < 0.001). Diagnostic accuracy of detecting early IVDD was better with UTE-T2* mapping than T2* mapping (P < 0.05),with receiver operating characteristic analysis area under the curve of 0.715–0.876.

Conclusions

UTE-T2* relaxometry provides another promising magnetic resonance imaging sequence for quantitatively evaluate lumbar IVDD and was more accurate than T2*mapping in the earlier stage degenerative process.
Comparison of the prognostic value of AJCC cancer staging system 7th and 8th editions for differentiated thyroid cancer
Authors: Morosán Allo Y. J. , Bosio L. , Morejón A. , Parisi C. , Faingold M. C. , Ilera V. , Gauna A. , Brenta G.
Published: June 2022

Background

In the last American Joint Committee on Cancer/Tumor, Node, Metastasis (AJCC/TNM) 8th edition (TNM8), several changes were introduced to this risk stratification system to improve the prognosis of differentiated thyroid cancer (DTC).

Aim

To validate the impact of TNM8 vs. TNM 7th edition (TNM7) in DTC in terms of predictive value in two hospitals from Buenos Aires, Argentina.

Methods

Retrospective study of DTC patients from two institutions. Reclassification from TNM7 to TNM8, disease-specific survival (DSS), and final clinical outcomes at the end of follow-up (recurrent/persistent structural disease) (median 5 years) were analyzed. The proportion of variation explained (PVE) was used to compare the predictive capability of DSS of both classification systems.

Results

Reclassification of 245 patients, aged (mean ± SD) 55 ± 15.36 years, 91% women, to TNM8 from TNM7 showed: 82% vs 57% stage I (SI), 10% vs 8.5% SII, 5% vs 22% SIII, 3% vs 12% SIV (p < 0.01). Forty percent of the population was downstaged with TNM8. Ten-year DSS rates for SI, SII, SIII and SIV in TNM7 were 100, 100, 100 and 74%, respectively and in TNM8: 97.6, 100, 100 and 37.5%, respectively. Out of 4 disease-specific deaths in SIV TNM7, one was subclassified to SI TNM8, corresponding to a 53-year-old patient with structural persistence. PVE for TNM8 (29%) was more than twice that of TNM7 (13%).

Conclusion

In this Argentinian DTC patients sample, it was confirmed that the new TNM8 classification is more accurate in predicting survival attributable to cancer than its previous version.
The effect of gum Arabic supplementation on cathelicidin expression in monocyte derived macrophages in mice
Authors: Siednamohammeddeen Nagat , Badi Rehab , Mohammeddeen Tahane , Enan Khalid , AmalSaeed
Published: June 2022

Background

Antimicrobial peptides (AMPs) are important effectors of the innate defense system. Cathelicidins, (CRAMP in mouse/rat, LL-37 in human) is one of the two major classes of AMPs in humans. The upregulation of LL-37 synthesis is a novel non-antibiotic approach to prevent or treat infectious diseases. Butyrate was found to induce Cathelicidin expression. Gum Arabic (GA), an exudate from Acacia senegaltree, is known for its prebiotic effects. Fermentation of GA by colonic bacteria increases serum butyrate concentrations. This study was conducted to investigate if GA supplementation can increase Cathelicidin expression in macrophages.

Methods

The study was an in-vivo experiment in mice. Thirty mice were randomly divided into three groups, ten mice per group. The two intervention groups received GA dissolved in drinking water in two different concentrations (15% w/v and 30% w/v) for 28 days. The third group served as a control. Blood was collected on Day 29 to isolate peripheral blood mononuclear cells (PBMC) which were cultured to obtain monocyte derived macrophages (MDMs). The transcription level of CRAMP was determined in MDMsby qPCR.

Results

We detected a significant increase (p = 0.023) in CRAMP expression in MDMs following 28 days of 15% GA supplementation, compared to the control group, but there was no significant change in the group on 30% GA supplementation (p = 0.055).

Conclusion

GAsupplementation can induce Cathelicidin expression in MDMs and the effect is dose dependent.
Home medication management problems and associated factors among psychiatric patients using home care pharmacy services at government hospitals in western Malaysia
Authors: Lau Christine Li Ling , Hor Cheah Yen , Ong Siew Ting , Roslan Muhammad Fadhlullah , Beh Xin Yi , Permal Dashnilatha , Rama Shamini
Published: June 2022

Background

Proper home medication management plays a role in improving medication adherence, preserving drug efficacy and ensuring safe medication practices, which is crucial to establish positive treatment outcomes. However, no published studies are available on home medication management among psychiatric patients. The study aimed to identify home medication management problems among psychiatric patients in Malaysia and to examine the associations of inappropriate medication storage and lack of a medication administration schedule with sociodemographic factors, disease insight, number of medications and type of home care pharmacy services (HCPS).

Methods

This multicentre cross-sectional study was conducted among psychiatric patients using HCPS in six government hospitals in western Malaysia. Data were extracted from the HCPS form used for each visit as per the protocol published by the Pharmaceutical Services Division, Ministry of Health Malaysia. A minimum sample size of 169 was needed. Proportional random sampling was applied. The associations of inappropriate medication storage and lack of medication administration schedule with study parameters were analysed using multiple logistic regressions.

Results

A total of 205 home visits were conducted with 229 home medication management problems identified; inappropriate medication storage and lack of medication administration schedule topped the list. Inappropriate medication storage was significantly associated with low income [AOR = 4.34 (95% CI 1.17:15.98),p = 0.027], alcohol consumption [AOR = 14.26 (95% CI 1.82:111.38),p = 0.011], poor insight [AOR = 2.34 (95% CI 1.08:5.06),p = 0.030] and part-time HCPS [AOR = 2.60 (95% CI 1.20:5.67),p = 0.016]. Lack of administration schedule was significantly associated with low income [AOR = 6.90 (95% CI 1.46:32.48),p = 0.014], smoking [AOR = 2.43 (95% CI 1.20:4.92),p = 0.013], poor insight [AOR = 5.32 (95% CI 2.45:11.56),p < 0.05] and part-time HCPS [AOR = 2.96 (95% CI 1.42:6.15),p = 0.004].

Conclusions

Inappropriate medication storage and a lack of a medication administration schedule are common among psychiatric patients. The study also highlighted the potential of HCPS to improve disease insight and home medication management among psychiatric patients if the service is utilized fully.
Phospholipid scramblase 1: a protein with multiple functions via multiple molecular interactors
Authors: Dal Col Jessica , Lamberti Marìa Julia , Nigro Annunziata , Casolaro Vincenzo , Fratta Elisabetta , Steffan Agostino , Montico Barbara
Published: June 2022

Phospholipid scramblase 1 (PLSCR1) is the most studied protein of the scramblase family. Originally, it was identified as a membrane protein involved in maintaining plasma membrane asymmetry. However, studies conducted over the past few years have shown the involvement of PLSCR1 in several other cellular pathways. Indeed, PLSCR1 is not only embedded in the plasma membrane but is also expressed in several intracellular compartments where it interacts with a diverse repertoire of effectors, mediators, and regulators contributing to distinct cellular processes. Although most PLSCR1 interactors are thought to be cell-type specific, PLSCR1 often exerts its regulatory functions through shared mechanisms, including the trafficking of different molecules within intracellular vesicles such as endosomes, liposomes, and phagosomes. Intriguingly, besides endogenous proteins, PLSCR1 was also reported to interact with exogenous viral proteins, thereby regulating viral uptake and spread. This review aims to summarize the current knowledge about the multiple roles of PLSCR1 in distinct cellular pathways.
Application of blood brain barrier models in pre-clinical assessment of glioblastoma-targeting CAR-T based immunotherapies
Authors: Huang Jez , Li Ying Betty , Charlebois Claudie , Nguyen Tina , Liu Ziying , Bloemberg Darin , Zafer Ahmed , Baumann Ewa , Sodja Caroline , Leclerc Sonia , Fewell Gwen , Liu Qing , Prabhakarpandian Balabhaskar , McComb Scott , Stanimirovic Danica B. , Jezierski Anna
Published: June 2022

Human blood brain barrier (BBB) models derived from induced pluripotent stem cells (iPSCs) have become an important tool for the discovery and preclinical evaluation of central nervous system (CNS) targeting cell and gene-based therapies. Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary form of gene-modified cell-based immunotherapy with potential for targeting solid tumors, such as glioblastomas. Crossing the BBB is an important step in the systemic application of CAR-T therapy for the treatment of glioblastomas and other CNS malignancies. In addition, even CAR-T therapies targeting non-CNS antigens, such as the well-known CD19-CAR-T therapies, are known to trigger CNS side-effects including brain swelling due to BBB disruption. In this study, we used iPSC-derived brain endothelial-like cell (iBEC) transwell co-culture model to assess BBB extravasation of CAR-T based immunotherapies targeting U87MG human glioblastoma (GBM) cells overexpressing the tumor-specific mutated protein EGFRvIII (U87vIII). Two types of anti-EGFRvIII targeting CAR-T cells, with varying tonic signaling profiles (CAR-F263 and CAR-F269), and control Mock T cells were applied on the luminal side of BBB model in vitro. CAR-F263 and CAR-F269 T cells triggered a decrease in transendothelial electrical resistance (TEER) and an increase in BBB permeability. CAR-T cell extravasation and U87vIII cytotoxicity were assessed from the abluminal compartment using flow cytometry and Incucyte real-time viability imaging, respectively. A significant decrease in U87vIII cell viability was observed over 48 h, with the most robust cytotoxicity response observed for the constitutively activated CAR-F263. CAR-F269 T cells showed a similar cytotoxic profile but were approximately four fold less efficient at killing the U87vIII cells compared to CAR-F263, despite similar transmigration rates. Visualization of CAR-T cell extravasation across the BBB was further confirmed using BBTB-on-CHIP models. The described BBB assay was able to discriminate the cytotoxic efficacies of different EGFRvIII-CARs and provide a measure of potential alterations to BBB integrity. Collectively, we illustrate how BBB models in vitro can be a valuable tool in deciphering the mechanisms of CAR-T–induced BBB disruption, accompanying toxicity and effector function on post-barrier target cells.
Racial disparities in triple negative breast cancer: toward a causal architecture approach
Authors: Siegel Scott D. , Brooks Madeline M. , Lynch Shannon M. , Sims-Mourtada Jennifer , Schug Zachary T. , Curriero Frank C.
Published: June 2022

Background

Triple negative breast cancer (TNBC) is an aggressive subtype of invasive breast cancer that disproportionately affects Black women and contributes to racial disparities in breast cancer mortality. Prior research has suggested that neighborhood effects may contribute to this disparity beyond individual risk factors.

Methods

The sample included a cohort of 3316 breast cancer cases diagnosed between 2012 and 2020 in New Castle County, Delaware, a geographic region of the US with elevated rates of TNBC. Multilevel methods and geospatial mapping evaluated whether the race, income, and race/income versions of the neighborhood Index of Concentration at the Extremes (ICE) metric could efficiently identify census tracts (CT) with higher odds of TNBC relative to other forms of invasive breast cancer. Odds ratios (OR) and 95% confidence intervals (CI) were reported;p-values < 0.05 were significant. Additional analyses examined area-level differences in exposure to metabolic risk factors, including unhealthy alcohol use and obesity.

Results

The ICE-Race, -Income-, and Race/Income metrics were each associated with greater census tract odds of TNBC on a bivariate basis. However, only ICE-Race was significantly associated with higher odds of TNBC after adjustment for patient-level age and race (most disadvantaged CT: OR = 2.09; 95% CI 1.40–3.13), providing support for neighborhood effects. Higher counts of alcohol and fast-food retailers, and correspondingly higher rates of unhealthy alcohol use and obesity, were observed in CTs that were classified into the most disadvantaged ICE-Race quintile and had the highest odds of TNBC.

Conclusion

The use of ICE can facilitate the monitoring of cancer inequities and advance the study of racial disparities in breast cancer.
Efficacy and safety of Gyejibokryeong-hwan (GBH) in major depressive disorder: study protocol for multicentre randomised controlled trial
Authors: Choi Yujin , Jung In Chul , Kim Ju Yeon , Cho Seung-Hun , Kim Yunna , Chung Sun-Yong , Kwak Hui-Yong , Lee Doo Suk , Lee Wonwoo , Nam In-Jeong , Yang Changsop , Lee Mi Young
Published: June 2022

Background

Gyejibokryeong-hwan (GBH) is an herbal medicine composed of five herbs. It has been widely used to treat gynaecological diseases in traditional East Asian medicine. Recent animal studies suggest antidepressant effects of GBH. In this trial, we explore the efficacy and safety of GBH in patients with major depressive disorder and to identify the optimal dose for the next phase III trial.

Methods

This trial will enrol 126 patients diagnosed with major depressive disorder and not treated with antidepressants. Participants will be randomised to receive a high or a low dose of GBH or placebo granules. The study drugs will be administered three times a day, for 8 weeks. The 17-item Hamilton Depression Rating Scale (HDRS) will be used to measure the severity of depressive symptoms at weeks 2, 4, 6, 8, and 12. The primary efficacy endpoint is the change from baseline in HDRS-17 total score post-treatment at week 8. Analysis of covariance will be based on the baseline HDRS-17 total score and site as the covariates. Safety assessment will be based on the frequency of adverse events. The severity and causality of the study drug will be assessed.

Discussion

This study is designed to evaluate the efficacy and safety of GBH granules compared with placebo in patients with major depressive disorder.

Trial registration

Clinical Research Information Service KCT0004417. Registered on November 1, 2019 (prospective registration)
Open chromatin analysis in Trypanosoma cruzi life forms highlights critical differences in genomic compartments and developmental regulation at tDNA loci
Authors: Lima Alex Ranieri Jerônimo , Silva Herbert Guimarães de Sousa , Poubel Saloe , Rosón Juliana Nunes , de Lima Loyze Paola Oliveira , Costa-Silva Héllida Marina , Gonçalves Camila Silva , Galante Pedro A. F. , Holetz Fabiola , Motta Maria Cristina Machado , Silber Ariel M. , Elias M. Carolina , da Cunha Julia Pinheiro Chagas
Published: June 2022

Background

Genomic organization and gene expression regulation in trypanosomes are remarkable because protein-coding genes are organized into codirectional gene clusters with unrelated functions. Moreover, there is no dedicated promoter for each gene, resulting in polycistronic gene transcription, with posttranscriptional control playing a major role. Nonetheless, these parasites harbor epigenetic modifications at critical regulatory genome features that dynamically change among parasite stages, which are not fully understood.

Results

Here, we investigated the impact of chromatin changes in a scenario commanded by posttranscriptional control exploring the parasite Trypanosoma cruzi and its differentiation program using FAIRE-seq approach supported by transmission electron microscopy. We identified differences in T. cruzi genome compartments, putative transcriptional start regions, and virulence factors. In addition, we also detected a developmental chromatin regulation at tRNA loci (tDNA), which could be linked to the intense chromatin remodeling and/or the translation regulatory mechanism required for parasite differentiation. We further integrated the open chromatin profile with public transcriptomic and MNase-seq datasets. Strikingly, a positive correlation was observed between active chromatin and steady-state transcription levels.

Conclusion

Taken together, our results indicate that chromatin changes reflect the unusual gene expression regulation of trypanosomes and the differences among parasite developmental stages, even in the context of a lack of canonical transcriptional control of protein-coding genes.
Zibotentan in systemic sclerosis-associated chronic kidney disease: a phase II randomised placebo-controlled trial
Authors: Stern Edward P. , Host Lauren V. , Wanjiku Ivy , Escott K. Jane , Gilmour Peter S. , Ochiel Rachel , Unwin Robert , Burns Aine , Ong Voon H. , Cadiou Helen , O’Keeffe Aidan G. , Denton Christopher P.
Published: June 2022

Background

We report results from a phase II randomised placebo-controlled trial assessing zibotentan, a highly selective endothelin receptor antagonist (ERA), in chronic kidney disease (CKD) secondary to systemic sclerosis (SSc).

Methods

This trial included three sub-studies: ZEBRA 1—a randomised placebo-controlled, double-blind trial of zibotentan in SSc patients with CKD2 or CKD3 (and glomerular filtration rate (GFR) >45 ml/min) over 26 weeks; ZEBRA 2A—a 26-week placebo-controlled, single-blind trial of zibotentan in scleroderma renal crisis patients not requiring dialysis; and ZEBRA 2B—an open label pharmacokinetic study of zibotentan in patients on haemodialysis.

Results

Sixteen patients were screened for ZEBRA 1. Of these, 6 patients were randomised to zibotentan and 7 to placebo. In ZEBRA 1, there were 47 non-serious adverse events (AE) during the trial. Twenty-seven occurred in the placebo group and 20 in the zibotentan group. One serious adverse event (SAE) occurred during ZEBRA1, in the placebo arm. Descriptive statistics did not suggest an effect of study drug on serum sVCAM1. Estimated GFR numerically declined in patients treated with placebo at 26 weeks and 52 weeks. In contrast, average eGFR increased in zibotentan-treated cases.

The 4 patients in ZEBRA 2A experienced 8 non-serious AEs, distributed equally between placebo and zibotentan. There was one SAE each in placebo and zibotentan groups, both unrelated to study medication.

ZEBRA 2B recruited 8 patients, 6 completed first dosing, and 2 completed a second dosing visit. Pharmacokinetic analysis confirmed zibotentan levels within the therapeutic range. Three patients experienced 3 non-serious AEs. One SAE occurred and was unrelated to study drug.

Conclusions

Zibotentan was generally well-tolerated. ZEBRA 1 did not show any effect of zibotentan on serum sVCAM-1 but was associated with numerical improvement in eGFR at 26 weeks that was more marked at 52 weeks. ZEBRA 2B suggested a feasible dose regimen for haemodialysis patients.

Trial registration

EudraCT no: 2013-003200-39 (first posted January 28, 2014)

ClinicalTrials.gov Identifier: NCT02047708

Sponsor protocol number: 13/0077
Clinical course of patients with rheumatoid arthritis who continue or discontinue biologic therapy after hospitalization for infection: a retrospective observational study
Authors: Kashiwado Yusuke , Kiyohara Chikako , Kimoto Yasutaka , Nagano Shuji , Sawabe Takuya , Oryoji Kensuke , Mizuki Shinichi , Nishizaka Hiroaki , Yoshizawa Seiji , Yoshizawa Shigeru , Tsuru Tomomi , Inoue Yasushi , Ueda Naoyasu , Ota Shun-ichiro , Suenaga Yasuo , Miyamura Tomoya , Tada Yoshifumi , Niiro Hiroaki , Akashi Koichi , Horiuchi Takahiko
Published: June 2022

Background

To analyse the subsequent clinical course of patients with rheumatoid arthritis (RA) who either continued or discontinued biologic agents after hospitalization for infections.

Methods

We retrospectively reviewed the clinical records of 230 RA patients with 307 hospitalizations for infections under biologic therapy between September 2008 and May 2014 in 15 institutions for up to 18 months after discharge. The risks of RA flares and subsequent hospitalizations for infections from 61 days to 18 months after discharge were evaluated.

Results

Survival analyses indicated that patients who continued biologic therapy had a significantly lower risk of RA flares (31.4% vs. 60.6%, P < 0.01) and a slightly lower risk of subsequent infections (28.7% vs. 34.5%, P = 0.37). Multivariate analysis showed that discontinuation of biologic therapy, diabetes, and a history of hospitalization for infection under biologic therapy were associated with RA flares. Oral steroid therapy equivalent to prednisolone 5 mg/day or more and chronic renal dysfunction were independent risk factors for subsequent hospitalizations for infections.

Conclusions

Discontinuation of biologic therapy after hospitalization for infections may result in RA flares. Continuation of biologic therapy is preferable, particularly in patients without immunodeficiency.
Well-differentiated cerebellum in an ovarian mature cystic teratoma: a case report and review of the literature
Authors: AlEssa Ahmed , AlAhmadi Hassan H. , Ahmed Ayesha , AlMousa Abdulatif , Hamadeh Nasreen G. , Farah Yasir A. Hassan
Published: June 2022

Background

Mature teratoma is the most common germ cell tumor as it represents 95% of germ cell tumors. Although common in children and young adults, ovarian teratoma can occur at any age. Mature teratomas are composed of mature tissues representing elements derived from more than one embryonic germ layer (ectoderm, mesoderm, and endoderm), with ectodermal derivatives being the usual predominant component; however, the finding of a well-differentiated cerebellum is extremely rare.

Case presentation

A 20-year-old Saudi female presented to the emergency department with severe abdominal pain of 1-day duration. Pelvic ultrasound showed a large ovoid- to bilobed-shaped cystic pelvic structure extending to the lower abdomen. The patient underwent left ovarian cystectomy. Microscopic examination showed a cyst wall with skin tissue, including adnexal structures (sebaceous glands), a well-differentiated cerebellum, and mature glial tissue. After extensive sampling, no immature component was identified. Thus, the final diagnosis of a mature cystic teratoma with well-differentiated cerebellum was established. The patient was well postoperatively and was discharged in a stable condition.

Conclusion

We report this case of well-differentiated cerebellum within ovarian teratoma to expand the pool of cases reported in literature of this extremely rare entity, as only 22 cases with such findings have been reported in literature to the best of our knowledge. This finding poses a diagnostic challenge to the pathologist due to its rarity and its similarity to immature teratoma. We thus emphasize that thorough sampling of ovarian teratoma is of paramount importance and to keep the aforementioned diagnosis in mind and not confuse it with immature elements, especially in intraoperative consultation and frozen sections.
Covid-19 and female migrants: policy challenges and multiple vulnerabilities
Authors: Nhengu Dudziro
Published: June 2022

To what extent has Covid-19 policy responses exacerbated the already existing multiple vulnerabilities of female migrants in Southern Africa? Using strategic conversations, the paper explores personal experiences of key conversants, to explore how gender blind policy responses to the pandemic have heightened female migrants’ socio-economic challenges. The paper recommends gender sensitive and context specific policy responses to mitigate the existing socio-economic challenges.
A new two-degree of freedom combined PID controller for automatic generation control of a wind integrated interconnected power system
Authors: Karanam Appala Naidu , Shaw Binod
Published: June 2022

Frequency control of an interconnected power system in the presence of wind integration is complex since wind speed/power variations also affect system frequency in addition to load perturbations. Therefore, improving existing control schemes is necessary to maintain a stable frequency in such complex power system scenarios. In this paper, a new 2-degree of freedom combined proportional-integral and derivative control scheme is applied to a wind integrated interconnected power system. In designing the controller, several inputs used for a secondary frequency control loop are considered along with the merits of the existing controllers. The combined controller provides better control action than existing controllers in the presence of wind as is evidenced by the wide variety of results presented. For tuning of the controller gains, a crow search optimization algorithm (CRSOA) is used. Results are obtained via the MATLAB/Simulink software.
Sphingolipids in plant immunity
Authors: Zeng Hong-Yun , Yao Nan
Published: June 2022

Sphingolipids (lipids with a sphingoid base backbone) are important components of eukaryotic membrane systems and key signaling molecules that are essential for controlling cellular homeostasis, acclimating to stress, and regulating plant immunity. Studies using sphingolipid treatments, measuring sphingolipids in infected plants, and functionally studying sphingolipid biosynthetic mutants demonstrated that sphingolipids participate in plant cell death and defense responses. In this review, we present an updated map of sphingolipid signaling and review recent progress in understanding the functions of sphingolipids in plant immunity as structural components of biological membranes, and as mediators of defense signaling. Moreover, several pressing questions, such as how sphingolipids in the plasma membrane, particularly microdomains, act to perceive pathogens and transduce signals during plant–pathogen interactions, remain to be further explored in future research.
Assessing aerodynamic loads on low-rise buildings considering Reynolds number and turbulence effects: a review
Authors: Khaled Md Faiaz , Aly Aly Mousaad
Published: June 2022

This paper presents an extensive review of existing techniques used in estimating design wind pressures considering Reynolds number and turbulence effects, as well as a case study of a reference building investigated experimentally. We shed light on the limitations of current aerodynamic testing techniques, provisions in design standards, and computational fluid dynamics (CFD) methods to predict wind-induced pressures. The paper highlights the reasons for obstructing the standardization of the wind tunnel method. Moreover, we introduce improved experimental and CFD techniques to tackle the identified challenges. CFD provides superior and efficient performance by employing wall-modeled large-eddy simulation (WMLES) and hybrid RANS-LES models. In addition, we tested a large-scale building model and compared the results with published small-scale data. The findings reinforce our hypothesis concerning the scaling issues and Reynolds number effects in aerodynamic testing.
Treatment of non-restrictive cor triatriatum sinister during concomitant cardiac surgery
Authors: Di Bacco Lorenzo , D’Alonzo Michele , Repossini Alberto , Zanin Francesca , Muneretto Claudio , Benussi Stefano
Published: June 2022

Background

Cor triatriatum is a rare congenital heart disease representing the 0.4% of all congenital cardiac anomalies. To date, no specific genetic alteration has been associated to cor triatriatum. The left-sided presentation (cor triatriatum sinister (CTS)) generally consists in a fibromuscular membrane that divides the left atrium into two chambers, therefore generating a varying grade of flow obstruction depending on the shape, location, and membrane fenestration size. Cor triatriatum sinister can be isolated or associated to other congenital heart defects such as ostium secundum atrial septal defect, patent foramen ovale or abnormal pulmonary veins drainage.

Case presentation

Our case is a 63-year-old woman who was diagnosed with a non-restrictive membrane during a hospitalization for acute heart failure. In the following 6 months, she started to become symptomatic. However, the onset of symptoms was more likely related to mitral valve regurgitation worsening and previously unknown coronary artery disease, rather than to CTS. She underwent bi-atrial surgical ablation (Cox Maze IV procedure) for atrial fibrillation (AF), surgical resection of interatrial membrane with mitral annuloplasty, and myocardial revascularization.

Conclusion

The onset and severity of symptoms in patients with CTS mostly depend on membrane fenestration size, grade of stenosis generated and pulmonary veins drainage site. However, some cases may remain asymptomatic until adulthood; the degree of pulmonary hypertension and congestive heart failure is determined by the presence of additional cardiac anomalies and the fibromuscular membrane fenestration. In some cases, CTS may remain asymptomatic, thus the diagnosis can be incidental.
Introduction to this special section: Physics-driven machine learning
Authors: Shaw Simon , Kaplan Sam , Li Chengbo
Published: June 2022

Machine learning has gained widespread popularity in fields such as research, finance, behaviorism, marketing, economics, and communications, where large volumes of training data are available and where an underlying model or system may not be readily accessible or easily parameterized. On the other hand, breakthroughs into scientific applications where underlying physical models exist and are well understood are harder to find. This is presumably because the physics-based solution, while imperfect, exploits the intrinsic relation between inputs and outputs and can often outperform a purely data-driven solution. Furthermore, adoption of machine learning may encounter resistance because these new algorithms are often opaque, and it is not always clear under what circumstances the methods will fail.
A hybrid physics and machine learning approach for velocity prediction
Authors: Liu Di , Zou Changchun , Song Qianggong , Wan Zhonghong , Zhao Haizhen
Published: June 2022

Elastic well logs play an important role in reservoir characterization in the subsurface. However, due to the high expense of drilling, only a few wells are drilled to limited depths, making it difficult to understand the deposition and execute geophysical activities such as building background models for seismic inversion and property models for seismic forward modeling. We begin with P-velocity prediction between the wells and extension along the wellbore to tackle this problem. A hybrid workflow is introduced based on seismic and available P-velocity logs, including well-log decomposition, relative rock physics, seismic forward modeling, feature engineering based on seismic transform, optimal attribute selection, and machine learning network training and prediction. In this hybrid workflow, relative P-velocity instead of absolute P-velocity is used for labeling. The rock-physics study and seismic forward modeling contribute to label augmentation. The machine learning approach assists in discovering the relationship between the relative P-velocity and the optimal seismic attributes. Under physics rules, the predicted relative velocity through the trained network is integrated with the compaction trend to estimate the final absolute velocity. This hybrid workflow is applied to a case study of sand-shale sequences in northern China. The model-based deterministic inversion and data-driven machine learning approaches are also compared. The results of blind well testing indicate that the data-driven approach lacks generalization capability and fails to predict extension in some blind wells. The physics-based inversion performs differently in blind wells in different locations. By contrast, P-velocity prediction with the hybrid workflow improves prediction accuracy in all blind wells, horizontally and vertically. The results indicate that this hybrid workflow promises interpolating and extending elastic well logs when the deposition environment does not vary significantly. Further studies are recommended to discuss the applicability of this workflow.
Downhole density estimation using multielement geochemistry and machine learning
Authors: Goodfellow Sebastian D. , Wei Nan , Drielsma Chris , Gerrie Vince , Petrie Larry
Published: June 2022

Machine learning (ML) was used to estimate bulk density from multielement geochemistry. At the Wheeler River site, host to the Phoenix and Gryphon uranium deposits, multielement geochemistry data were acquired for 829 exploration holes. Of those holes, 41 were logged with a downhole dual-spaced density probe during several mobilizations between 2009 and 2019. Density measurements were collected to provide constraints for inversions of airborne gravity data. To improve the density model's spatial resolution, ML models were trained to estimate bulk density from collocated multielement geochemistry data. Two geochemical laboratory methods were used (251 holes for the old method and 578 holes for the new method); therefore, two separate models were trained. Leave-one-hole-out cross-validation mean absolute error (MAE) results from the old and new geochemistry models showed similar scores of 0.027 g/cm3 and 0.025 g/cm3, respectively. Eight test holes were removed from the training data and used for final evaluation once the model was trained. Test hole results showed MAE scores of 0.026 g/cm3 for the old geochemistry model and 0.043 g/cm3 for the new geochemistry model. A unique aspect of this data set was the presence of repeat logs for multiple boreholes over a decade-long logging campaign. This provided the opportunity to assess the measurement uncertainty across time, density probes, operators, and boreholes conditions. The process of estimating downhole density from multielement geochemistry data could be used for many exploration projects to help generate better starting density models for use in geophysical inversions and other applications.