bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma NTPDase1 Activity Regulates Platelet Purinergic Signaling in Sickle Cell Disease
Authors: Brzoska Tomasz , Menchikova Elizaveta V , Kaminski Tomasz W. , Vats Ravi , Tutuncuoglu Egemen , Tofovic Stevan P. , Jackson Edwin K. , Gladwin Mark T. , Sundd Prithu
Published: November 2021

Acute systemic painful vaso-occlusive episode (VOE) often serves as an antecedent to acute chest syndrome (ACS), which is a type of acute lung injury and the leading cause of mortality among sickle cell disease (SCD) patients. Based on clinical epidemiology, ACS is often preceded by thrombocytopenia and involves massive thrombosis across pulmonary artery branches in 10-20% of ACS patients. Although, released during hemolysis, adenosine diphosphate (ADP) is known to activate platelets by stimulating their P2Y1 and P2Y12 purinergic receptors, antagonists of P2Y12 have not shown any benefit in ACS therapy, justifying the need for better understanding of purinergic signaling in SCD. Ecto-nucleoside-tri-phosphate-diphosphohydrolase-1 (E-NTPDase1; CD39) maintains ADP homeostasis by degrading excessive ADP. Though CD39 inhibits ADP-dependent platelet activation and vascular thrombosis, its role in ASC is still unidentified.

Here, we use intravital lung microscopy in transgenic humanized SCD mice to show that intravascular (IV) administration of ADP triggered pulmonary thrombosis in control mice but failed to trigger pulmonary thrombosis in SCD mice. Identical to intravital findings, IV ADP administration also evoked transient thrombocytopenia in control but not SCD mice, while, IV collagen led to comparable drop in platelet count in both SCD and control mice. In vitro turbidimetric aggregation study yet again demonstrated impaired SCD mouse platelet response to ADP, which was significantly augmented by CD39 inhibitor (sodium metatungstate, POM-1). Indeed, we found significantly higher plasma levels and activity of CD39 in SCD mice compared to control mice using ELISA and malachite green assays, respectively. Hemin, a major host-derived damage associated molecular pattern (DAMP) in SCD, was incubated with Human Lung MicroVascular Endothelial Cell (HMVEC-L) to assess CD39 expression using western blotting. Hemin (10 -100 µM) in a dose dependent manner decreased CD39 levels in HMVEC-L.

Our current findings suggest that elevated CD39 plasma levels and activity possibly prevents ADP-mediated platelet aggregation and pulmonary thrombosis in SCD. We demonstrated that SCD milieu promotes loss of endothelial CD39, which may be directly associated with increased CD39 plasma levels and activity. Current study explains why P2Y12 blockers are not effective in SCD therapy and warrant the need for further studies to understand the role of purinergic signaling in pathogenesis of ACS.

Disclosures

Sundd: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring Inc: Research Funding; Bayer: Research Funding.
Survival Trend of Waldenstrom Macroglobulinemia over Last 3 Decade Shows Health Disparities in Minority Population
Authors: Madhira Bhaskara Reddy , Durer Seren , Ghimire Krishna
Published: November 2021

Introduction:

Waldenstrom macroglobulinemia (WM) is a rare and incurable lymphoma. There have been significant changes in management of WM over last decade with incorporation of monoclonal antibodies, and other novel therapies. We conducted this study to evaluate survival rate among patients with WM.

Methods:

We selected patients with WM diagnosed during 1992-2018 from Surveillance, Epidemiology and End Results (SEER) 13 database. We analyzed 1- and 5-years relative survival (RS) rates using SEER*stat program. We used Z test to compare relative survival trend over 3 decades (1 st: 1992-2000, 2 nd: 2001-2010, 3 rd: 2011-2018) among patients with WM by race (white, other), age (>18 years, 18-64 years and >65 years) and sex.

Results:

A total of 5,690 (1,582; 2,141; and 1,967) adults patients were diagnosed with WM during 1992-2018 (1 st, 2 nd, and 3 rd decades), 86% were white and 14% were other races combined. There were 1,959 and 3,731 patients in age group (18-64 and >65years) respectively. During 1 st, 2nd and 3 rd decades examined, 1 and 5 year RS in patients with WM were (87.3%, 92.0% and 94.7%) and (67.7%, 81.3%, and 85.7%) respectively. Improvement in RS was noted in both younger and older age group and sex examined. (Table 1)

White patients with WM have 1 and 5 year RS (87.3%, 92.6%, 95.1%) and (68.2%, 82.1%, 86.3%). This improvement RS over 3 decades was statistically significant with Z value >1.65/P value <0.05. Other races with WM have 1 and 5 year RS (86.5%, 86.9%, 90.4%) and (64.3%, 72.3%, 78.1%) during 1 st, 2nd and 3 rd decades.

Conclusion: This study showed that relative survival rates of WM have significantly improved over past 3 decades. Improvement in survival trend was mainly driven by white patients. Patients with other races do not have statistically significant improvement in relative survival rates during last 3 decades. Health disparities in minority population with WM warrants further research.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
Frequency and Survival of T-Cell Lymphomas in Peru: Initial Report of a Peruvian Registry Experience
Authors: Enriquez Daniel J , Casas Jhoisy , Sandival Gustavo , Espino Johan , Espinoza-Morales Evelyn , Cervantes Elizabeth , Castro-Mollo Melanie , Jiménez-Mozo Fátima , Dueñas Daniela , Barrionuevo Carlos , Haro Juan C , Ortega Emperatriz , Roque Katia , Vidaurre Tatiana , Lozano Sophia , Quintana Shirley , Vasquez Jule , Lopez Lourdes , Alcarraz Cindy , Diaz Alonso , Flores Claudio , Samanez-Figari Cesar
Published: November 2021

Introduction: T-cell lymphomas are a relatively rare and heterogeneous group of lymphoid neoplasms. Its incidence relies on viral infections incidence as Human T-cell lymphotropic virus type I-II (HTLV-I/II) and Ebstein Bar virus (EBV). Specifically, these viruses have a significantly higher incidence in Latin-American populations. Our objective was to calculate the incidence and survival of T-cell lymphomas in the largest Peruvian population based on a national registry. Methods: We conducted a multicenter, retrospective registry study of non-Hodgkin T cell lymphoma. The data was extracted from Instituto Nacional de Enfermedades Neoplasicas and Oncosalud-AUNA, Lima-Peru, from January 2010 to December 2019, a total of 948 patients who were diagnosed as mature T cell non-Hodgkin lymphoma based on the World Health Organization Classification 2008 were enrolled. T-lymphoblastic lymphoma/leukemia was excluded. Overall survival was calculated based on death dates from the Peruvian national identification registry (RENIEC).

Results: The median age was 51 years (range, 1-94), and male and female patients were 512 (54%) and 436 (46%). Among the 948 patients enrolled, Peripheral T-cell lymphoma was the common neoplasm accounting for 23% (n=221), and Extra-Nodal NK T-lymphoma (22%, n=213), Adult T-cell lymphoma (22%, n=205), Anaplasic Large cell lymphoma (14%, n=131), Cutaneous T-cell lymphoma (14%, n=129) (Figure 1a). At the time of diagnosis, extranodal disease was found in 68.6% (650) of patients. By July 2021, only 15.3% of cases were in remission and 37% (350) were alive. Median global overall survival of T-cell lymphomas was 1 year (0.8-1.1), Cutaneous T-cell lymphoma had the highest survival and Adult T-cell lymphoma had the lowest survival (Table 1 and Figure 1b).

Conclusion: This initial report shows a relatively high frequency of mature T-cell lymphomas in Latin-America real-world setting, and confirms that T-cell lymphomas patients had a dismal outcome. The clinical outcome for patients with T-cell lymphomas subtypes is poor with standard therapies, and novel agents and new modalities are needed to improve survival.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
Ing4-Deficiency Enhances Hematopoietic Stem Cell Quiescence and Confers Resistance to Inflammatory Stress
Authors: Thompson Zanshé , Anderson Georgina A , Gabriel Seth , Rodriguez Melanie , Binder Vera , Kathrein Katie L
Published: November 2021

In a screen for epigenetic regulators of hematopoiesis in zebrafish, we identified a requirement of the tumor suppressor protein, Ing4, in hematopoietic stem and progenitor cell (HSPC) specification. Though the Ing4 mechanism of action remains poorly characterized, loss of Ing4 has been shown to promote stem cell-like characteristics in malignant cells and it is a frequent target of inactivation in various types of cancer. Mutations in Ing4 cause deregulation of both NF-kB and c-Myc target gene expression. We have also identified a requirement for Ing4 in murine hematopoiesis. Ing4-/- mice have aberrant hematopoiesis and elevated cytokine expression in bone marrow cells. Using RNA-sequencing, we found that Ing4-deficient HSPCs express high levels of c-Myc target genes and genes associated with oxidative phosphorylation and ribosomal biogenesis. Yet, Ing4 deficiency induces G 0 arrest in HSPCs and they have low levels of reactive oxygen species. This places Ing4-deficient HSPCs in a poised state, where they are quiescent, but express elevated levels of genes associated with differentiation. Under stress hematopoiesis following low-dose irradiation, Ing4-deficient long-term hematopoietic stem cells (LT-HSCs) do not expand, but short-term hematopoietic stem cells (ST-HSCs) function comparably to wild-type. Similarly, under transplantation stress, LT-HSCs fail to contribute to multilineage chimerism, while ST-HSCs contribute at levels equal to wild-type cells. These results are striking, particularly when compared to other models of enhanced NF-kB activity, where HSPCs cannot contribute to multilineage chimerism in transplantation. We sought to target the misregulated pathways in Ing4-deficient HSCs to rescue to effects of Ing4 deficiency. To this end, we chose to target the c-Myc pathway for several reasons: c-Myc target genes are over-represented in our RNA-seq data, c-Myc lies upstream of several of the misregulated pathways observed in Ing4-/- HSCs, and Ing4 has previously been reported to negatively regulate c-Myc activity directly. When treated with the c-Myc inhibitor, 10058-F4, both LT-HSCs and ST-HSCs are pushed into cycling, but this treatment also resulted in fewer cells overall. These results suggest that dampening of the c-Myc pathway can partially rescue Ing4 loss of function. Overall, our findings suggest that Ing4 plays a crucial role in the regulation of hematopoiesis and provides key tools for further identification and characterization of Ing4 pathways and functions. Given the role of Ing4 in both normal hematopoiesis and cancer, this gene likely has a critical role in regulation of stem cell self-renewal and maintenance.

Disclosures

No relevant conflicts of interest to declare.
Novel CRISPR-Associated Gene-Editing Systems Discovered in Metagenomic Samples Enable Efficient and Specific Genome Engineering for Cell Therapy Development
Authors: Cost Gregory J. , Lamothe Rebecca C. , Storlie Meghan D. , Rivas Andres , Espinosa Diego A. , Goltsman Daniela S. A. , Alexander Lisa , Butterfield Cristina N. , Brown Christopher T. , Thomas Brian C.
Published: November 2021

Gene-editing technology has revolutionized molecular therapeutics, enabling DNA-engineering-based approaches to treat disease. Despite this, development of medicines using gene editing has been hampered by technological, immunological, and legal limitations. We described previously the discovery of novel type II and type V gene-editing systems from metagenomic data, the characterization of these systems in vitro, and a demonstration of their activity in immortalized cell lines. Here, we substantially advance this work with three separate, novel gene-editing systems, demonstrating their utility for cell therapy development. We express and purify the nuclease components of both type II and type V effectors and show that all three systems are capable of reproducible, high-frequency gene editing in primary immune cells. In human T cells, disruption of the T cell receptor (TCR) alpha-chain constant region occurred in up to 95% of cells, both copies of the TCR beta-chain constant region in up to ~90% of cells, and beta-2 microglobulin in up to 95% of cells. Simultaneous double knock-out of TRAC and TRBC was obtained at an equal frequency. Gene editing with our systems had no effect on T cell viability. Further, we use our novel gene-editing systems to exploit homology-dependent DNA repair to integrate a CAR construct into the TCR alpha-chain locus (in up to ~60% of T cells), and demonstrate high-level CAR expression and antigen-dependent CAR-T cytotoxicity. Such robust editing activity at the TCR loci will permit efficient engineering and manufacture of allogeneic chimeric antigen receptor- (CAR) and TCR-based cell therapies.

We next applied our novel gene-editing tools to NK cells and B cells. We achieved almost 100% gene disruption at the CD38 locus in NK cells and integrated a chimeric antigen receptor into the NK cell genome at a frequency of ~40%. Such CAR-NK cells displayed robust CAR-directed cellular cytotoxicity. B cell editing occurred in approximately 80% of target cells with successful transgene integration.

Cas9 is notorious for tolerating mismatches and bulges in its target, resulting in high levels of unwanted DNA double-strand break formation. In contrast, interrogation of our gene editing systems using GUIDE-seq reveals no or very few off-target sites even at doses greatly in excess of those required for high-frequency gene editing. Finally, as our systems are taken from microbes found in environmental samples rather than from human pathogens, we expect pre-existing immunity to our nucleases will be quite rare. In all, we show that three new gene-editing systems have the activity, specificity, and translatability necessary for use in cell therapy development.

Disclosures

No relevant conflicts of interest to declare.
Machine learning approaches to predict the Plant-associated phenotype of Xanthomonas strains
Authors: te Molder Dennie , Poncheewin Wasin , Schaap Peter J. , Koehorst Jasper J.
Published: November 2021

Background

The genus Xanthomonas has long been considered to consist predominantly of plant pathogens, but over the last decade there has been an increasing number of reports on non-pathogenic and endophytic members. As Xanthomonas species are prevalent pathogens on a wide variety of important crops around the world, there is a need to distinguish between these plant-associated phenotypes. To date a large number of Xanthomonas genomes have been sequenced, which enables the application of machine learning (ML) approaches on the genome content to predict this phenotype. Until now such approaches to the pathogenomics of Xanthomonas strains have been hampered by the fragmentation of information regarding pathogenicity of individual strains over many studies. Unification of this information into a single resource was therefore considered to be an essential step.

Results

Mining of 39 papers considering both plant-associated phenotypes, allowed for a phenotypic classification of 578 Xanthomonas strains. For 65 plant-pathogenic and 53 non-pathogenic strains the corresponding genomes were available and de novo annotated for the presence of Pfam protein domains used as features to train and compare three ML classification algorithms; CART, Lasso and Random Forest.

Conclusion

The literature resource in combination with recursive feature extraction used in the ML classification algorithms provided further insights into the virulence enabling factors, but also highlighted domains linked to traits not present in pathogenic strains.
The thiol-disulfide exchange activity of AtPDI1 is involved in the response to abiotic stresses
Authors: Lu Ying , Yuan Li , Zhou Zhou , Wang Mengyu , Wang Xiaoyun , Zhang Shizhong , Sun Qinghua
Published: November 2021

Background

Arabidopsis protein disulfide isomerase 1 (AtPDI1) has been demonstrated to have disulfide isomerase activity and to be involved in the stress response. However, whether the anti-stress function is directly related to the activities of thiol-disulfide exchange remains to be elucidated.

Results

In the present study, encoding sequences of AtPDI1 of wild-type (WT) and double-cysteine-mutants were transformed into an AtPDI1 knockdown Arabidopsis line (pdi), and homozygous transgenic plants named pdi-AtPDI1, pdi-AtPDI1m1 and pdi-AtPDI1m2 were obtained. Compared with the WT and pdi-AtPDI1, the respective germination ratios of pdi-AtPDI1m1 and pdi-AtPDI1m2 were significantly lower under abiotic stresses and exogenous ABA treatment, whereas the highest germination rate was obtained with AtPDI1 overexpression in the WT (WT- AtPDI1). The root length among different lines was consistent with the germination rate; a higher germination rate was observed with a longer root length. When seedlings were treated with salt, drought, cold and high temperature stresses, pdi-AtPDI1m1, pdi-AtPDI1m2 and pdi displayed lower survival rates than WT and AtPDI1 overexpression plants. The transcriptional levels of ABA-responsive genes and genes encoding ROS-quenching enzymes were lower in pdi-AtPDI1m1 and pdi-AtPDI1m2 than in pdi-AtPDI1.

Conclusion

Taken together, these results clearly suggest that the anti-stress function of AtPDI1 is directly related to the activity of disulfide isomerase.
A survey of current practices, attitudes and demands of anaesthesiologists regarding the depth of anaesthesia monitoring in China
Authors: Zhan Jian , Yi Ting-Ting , Wu Zhuo-Xi , Long Zong-Hong , Bao Xiao-Hang , Xiao Xu-Dong , Du Zhi-Yong , Wang Ming-Jun , Li Hong
Published: November 2021

Background

In this study, we aimed to analyse survey data to explore two different hypotheses; and for this purpose, we distributed an online survey to Chinese anaesthesiologists. The hypothetical questions in this survey include: (1) Chinese anaesthesiologists mainly use the depth of anaesthesia (DoA) monitors to prevent intraoperative awareness and (2) the accuracy of these monitors is the most crucial performance factor during the clinical daily practice of Chinese anaesthesiologists.

Methods

We collected and statistically analysed the response of a total of 12,750 anesthesiologists who were invited to participate in an anonymous online survey. The Chinese Society of Anaesthesiologists (CSA) trial group provided the email address of each anaesthesiologist, and the selection of respondents was random from the computerized system.

Results

The overall response rate was 32.0% (4037 respondents). Only 9.1% (95% confidence interval, 8.2-10.0%) of the respondents routinely used DoA monitors. Academic respondents (91.5, 90.3-92.7%) most frequently used DoA monitoring to prevent awareness, whereas nonacademic respondents (88.8, 87.4-90.2%) most frequently used DoA monitoring to guide the delivery of anaesthetic agents. In total, the number of respondents who did not use a DoA monitor and whose patients experienced awareness (61.7, 57.8-65.6%) was significantly greater than those who used one or several DoA monitors (51.5, 49.8-53.2%). Overall, the crucial performance factor during DoA monitoring was considered by 61.9% (60.4-63.4%) of the respondents to be accuracy. However, most respondents (95.7, 95.1-96.3%) demanded improvements in the accuracy of the monitors for DoA monitoring. In addition, broad application in patients of all ages (86.3, 85.2-87.4%), analgesia monitoring (80.4, 79.2-81.6%), and all types of anaesthetic agents (75.6, 74.3-76.9%) was reported. In total, 65.0% (63.6-66.5%) of the respondents believed that DoA monitors should be combined with EEG and vital sign monitoring, and 53.7% (52.1-55.2%) believed that advanced DoA monitors should include artificial intelligence.

Conclusions

Academic anaesthesiologists primarily use DoA monitoring to prevent awareness, whereas nonacademic anaesthesiologists use DoA monitoring to guide the delivery of anaesthetics. Anaesthesiologists demand high-accuracy DoA monitors incorporating EEG signals, multiple vital signs, and antinociceptive indicators. DoA monitors with artificial intelligence may represent a new direction for future research on DoA monitoring.
Survival after traumatic out-of-hospital cardiac arrest in Vietnam: a multicenter prospective cohort study
Authors: Do Son Ngoc , Luong Chinh Quoc , Pham Dung Thi , Nguyen My Ha , Ton Tra Thanh , Hoang Quoc Trong Ai , Nguyen Dat Tuan , Pham Thao Thi Ngoc , Hoang Hanh Trong , Khuong Dai Quoc , Nguyen Quan Huu , Nguyen Tuan Anh , Tran Tung Thanh , Vu Long Duc , Van Nguyen Chi , McNally Bryan Francis , Ong Marcus Eng Hock , Nguyen Anh Dat
Published: November 2021

Background

Pre-hospital services are not well developed in Vietnam, especially the lack of a trauma system of care. Thus, the prognosis of traumatic out-of-hospital cardiac arrest (OHCA) might differ from that of other countries. Although the outcome in cardiac arrest following trauma is dismal, pre-hospital resuscitation efforts are not futile and seem worthwhile. Understanding the country-specific causes, risk, and prognosis of traumatic OHCA is important to reduce mortality in Vietnam. Therefore, this study aimed to investigate the survival rate from traumatic OHCA and to measure the critical components of the chain of survival following a traumatic OHCA in the country.

Methods

We performed a multicenter prospective observational study of patients (> 16 years) presenting with traumatic OHCA to three central hospitals throughout Vietnam from February 2014 to December 2018. We collected data on characteristics, management, and outcomes of patients, and compared these data between patients who died before hospital discharge and patients who survived to discharge from the hospital.

Results

Of 111 eligible patients with traumatic OHCA, 92 (82.9%) were male and the mean age was 39.27 years (standard deviation: 16.38). Only 5.4% (6/111) survived to discharge from the hospital. Most cardiac arrests (62.2%; 69/111) occurred on the street or highway, 31.2% (29/93) were witnessed by bystanders, and 33.7% (32/95) were given cardiopulmonary resuscitation (CPR) by a bystander. Only 29 of 111 patients (26.1%) were taken by the emergency medical services (EMS), 27 of 30 patients (90%) received pre-hospital advanced airway management, and 29 of 53 patients (54.7%) were given resuscitation attempts by EMS or private ambulance. No significant difference between patients who died before hospital discharge and patients who survived to discharge from the hospital was found for bystander CPR (33.7%, 30/89 and 33.3%, 2/6, P > 0.999; respectively) and resuscitation attempts (56.3%, 27/48, and 40.0%, 2/5, P = 0.649; respectively).

Conclusion

In this study, patients with traumatic OHCA presented to the ED with a low rate of EMS utilization and low survival rates. The poor outcomes emphasize the need for increasing bystander first-aid, developing an organized trauma system of care, and developing a standard emergency first-aid program for both healthcare personnel and the community.
Disability and the risk of subsequent mortality in elderly: a 12-year longitudinal population-based study
Authors: Yang Yang , Du Zhaohui , Liu Yafei , Lao Jiahui , Sun Xiaoru , Tang Fang
Published: November 2021

Background

Assessment the impact of disability on mortality among the elderly is vital to healthy ageing. The present study aimed to assess the long-term influence of disability on death in the elderly based on a longitudinal study.

Method

This study used the Chinese Longitudinal Healthy Longevity Study (CLHLS) data from 2002 to 2014, including 13,666 participants aged 65 years and older in analyses. The Katz ADL index was used to assess disability status and levels. Cumulative mortality rates were estimated by the Kaplan-Meier method. Cox proportional hazards models were conducted to estimate associations between disability and all-cause mortality for overall participants, two age groups as well as specific chronic disease groups. All reported results were adjusted by survey weights to account for the complex survey design.

Results

During the 12-year follow-up, the death density was 6.01 per 100 person-years. The 3-years’ cumulative mortality rate of nondisabled elderly was 11.9% (95%CI: 10.9, 12.9%). As the level of disability increased, the cumulative mortality rate was from 28.1% (95%CI: 23.0, 33.1%) to 77.6% (95%CI: 63.8, 91.4%). Compared with non-disabled elderly, the multiple-adjusted hazard ratio of death due to disability was 1.68 (95% CI: 1.48, 1.90). The hazard ratios varied from 1.44 (95%CI: 1.23, 1.67) to 4.45 (95%CI: 2.69, 7.38) after classifying the disability levels. The hazard ratios of death in the young-old group (65–79 years) were higher than the old-old group (80 years and over) in both level B (HR = 1.58, 95%CI: 1.25, 2.00 vs. HR = 1.22, 95%CI: 1.06, 1.39, P = 0.029) and level G (HR = 24.09, 95%CI: 10.83, 53.60 vs. HR = 2.56, 95%CI: 1.75, 3.74, P < 0.001). For patients with hypertension, diabetes, heart disease, cerebrovascular disease as well as dementia, disability increases their relative risk of mortality by 1.64 (95%CI: 1.40, 1.93), 2.85 (95%CI: 1.46, 5.58), 1.45 (95%CI: 1.02, 2.05), 2.13 (95%CI: 1.54, 2.93) and 3.56 (95%CI: 1.22, 10.38) times, respectively.

Conclusions

Disability increases the risk of all-cause death in the elderly, especially those with chronic diseases and the young-old group. Further studies are needed to better understand how to effectively prevent disability in the older population.
Refractive errors and risk factors for myopia in infants aged 1–18 months in Tianjin, China
Authors: Huo Lu , Qi Yuanyuan , Zhao Shaozhen
Published: November 2021

Background

Infancy is the of a child’s visual development. Refractive errors, especially myopia, are a common vision disorder. Thus, the purpose of this study was to explore refractive errors and risk factors for myopia among infants aged 1–18 months in Tianjin, China.

Methods

A total of 583 infants aged 1–18 months participated in this cross-sectional study at Tianjin Women’s and Children’s Health Center in China from February 2019 to November 2020. Each infant received a complete ophthalmologic examination, and myopia-related risk factors were investigated using a questionnaire.

Results

A total of 583 eligible infants participated in this study, including 312 (53.5%) boys and 271 (46.5%) girls. There were 164 (28.1%) premature born infants. The mean age was 6.59 ± 4.84 months (range, 1–18 months). The mean spherical equivalent (MSE) for the right eye was 1.81 D ± 1.56 D, with no difference related to sex (P = 0.104). Refractive state showed an average hyperopia of +2.74 ± 1.74 D at early ages, followed by a trend toward less hyperopia, finally reaching +1.35 ± 1.44 D at the age of 18 months (P ≤0.001). The overall prevalence rates of myopia (MSE ≤ −0.50 D), emmetropia (−0.50 D<MSE<+0.50 D), hyperopia (MSE ≥ +2.00 D), and astigmatism (≥ 1.50 D) were 5.1%, 10.8%, 42.7%, and 49.9%, respectively. The chi-square tests showed that gender, gestational age ≥37 weeks, winter birth, prenatal exposure to environmental tobacco smoke, and parental history of high myopia were associated with children’s myopia (P = 0.022, P = 0.023, P = 0.038, P = 0.015, P<0.001, respectively).

Conclusions

Among Chinese infants in Tianjin, hyperopia and astigmatism were the most frequent refractive errors, and the diopter was lower in individuals with higher age. In a small number of infants with myopia, genetic factors and the prenatal environment were associated with the early onset of myopia.
The road beyond licensing: the impact of a driver licensing support program on employment outcomes for Aboriginal and Torres Strait Islander Australians
Authors: Porykali Bobby , Cullen Patricia , Hunter Kate , Rogers Kris , Kang Melissa , Young Nareen , Senserrick Teresa , Clapham Kathleen , Ivers Rebecca
Published: November 2021

Background

With increasingly tough graduated driver licensing laws in all Australian States and Territories, driver licensing support programs are recognised as being important to support Aboriginal and Torres Strait Islander peoples to obtain a driver licence. Such programs appear to improve licensing attainment rates, but few studies have examined the broader impact that these programs can have. This research aims to 1) examine the impact of a New South Wales (NSW) based driver licensing support program (Driving Change) on client employment outcomes; 2) assess the influence of geographical area of program delivery on driver licence attainment.

Methods

Driving Change was delivered from February 2013 to August 2016 in 4 urban and 7 regional Aboriginal communities of NSW. Clients were followed-up at 6 months or more following contact with the program as part of routine program operations. Descriptive statistics and regression models were used to analyse data.

Results

From 933 clients contacted 254 agreed to provide feedback, a response rate of 27%. Those that responded were mostly female (57%), aged 24 years and under (72%), unemployed (85%) with secondary education or less (71%) and from a regional area (74%).

Adjusted logistic regression indicated that clients who achieved an independent licence were more likely (OR: 2.5, 95% CI: 1.22–5.24, p = 0.011) of reporting a new job or change in job than those who did not attain a licence. Clients from regional areas were more likely (OR: 1.72, 95% CI: 1.27–2.33, p < 0.001) to gain an independent licence than those from urban areas. There was no difference in employment outcomes (OR: 1.2, 95% CI: 0.53–2.52, p = 0.719) for clients from urban compared to regional areas.

Conclusion

The Driving Change program appears to be effective in improving employment outcomes for those who gained a licence. Clients from regional areas were more likely to gain a licence compared to those in urban settings, and were predominantly young and unemployed, often a hard to reach cohort. Future licensing programs being delivered in regional areas need integrated pathways into employment opportunities to provide holistic services that address the social and economic challenges faced by Aboriginal and Torres Strait Islander Australians.
Perceptions of females about trauma-informed services for survivors of sexual violence in south western Uganda- a qualitative study
Authors: Amwiine Earnest , Ainembabazi Bonita , Obwona Isaiah , Opoka Richard , Akatuhumuriza Mary , Niyonzima Vallence , Mubangizi Vincent
Published: November 2021

Background

Sexual violence is a public health concern globally and locally, and trauma-informed services are put in place to mitigate its consequences. A few studies have evaluated the quality and uptake of these trauma-informed services for sexual violence. This study aimed at; i) assessing the knowledge of participants about trauma-informed services, ii) exploring the attitudes of females about trauma-informed services, and iii) assessing different factors associated with the utilization of trauma-informed services.

Methods

This study employed a descriptive cross-sectional qualitative design. The participants were females at Kyangyenyi health center III and Kigarama health center III in Sheema district, southwestern Uganda. We used a purposive sampling procedure for all participants and then a consecutive sampling of females. Data about; knowledge of trauma-informed services for sexual violence, attitudes towards trauma-informed services, and factors influencing the utilization of trauma-informed services were collected using an in-depth interview guide. Data were analyzed using thematic content analysis.

Results

We interviewed 32 participants. There was a high prevalence of sexual violence, and it was a big concern in the community. Many of the respondents were not sensitized about trauma-informed services. Most of them knew only about HIV treatment. Our study shows that a good section of females did not seek the services after being sexually violated due to the fear of the perpetrator, bribing of the family of the affected and authorities, or even fear of family breakup and stigmatization. There were a lot of bribery, poor road networks, and inadequate health care services. These hindered survivors of sexual violence from utilizing trauma-informed services.

Conclusions

There was a knowledge gap about trauma-informed services for survivors of sexual violence. There was sexual violence in the community. Sensitization needs to be done among the populations by respective authorities to iron out issues of ignorance about the services and health workers evaluated for competence in offering the trauma-informed services.
Effects of autologous concentrated growth factor on gingival thickness in periodontal accelerated osteogenic orthodontics: a 6-month randomized controlled trial
Authors: Qi Lei , Ge Weiwen , Cao Ningning , Wang Shoupeng , Qian Yifeng , Wang Xudong , Zhang Lei
Published: November 2021

Background

Earlier studies have not given clear results of concentrated growth factor (CGF) on gingival thickness (GT) in periodontal accelerated osteogenic orthodontics (PAOO). This randomized controlled trial aimed to evaluate the effects of CGF on GT in patients with thin gingival phenotype undergoing PAOO.

Methods

Forty four patients presenting 264 anterior mandibular teeth were recruited and randomly allocated to one of the groups: test—positioning of autologous CGF after PAOO or control—positioning of a collagen membrane after PAOO. GT, gingival height (GH), buccal alveolar bone thickness (BT), and buccal alveolar bone height (BH) were evaluated depending on cross-sectional CBCT images at t0 (before surgery) and t1(6 months after surgery).

Results

GT were increased in both groups at t1 compared to t0. Yet, higher values were observed in the test group (from 0.94 ± 0.23 to 1.31 ± 0.33 mm) compared to the control group (from 0.94 ± 0.19 to 1.02 ± 0.16 mm) (p < 0.05). Moreover, in the intergroup comparison, GT at t1 in the test group was significantly higher compared to the control group (p < 0.01). Furthermore, the GT of central incisors, lateral incisors and canine teeth all showed significantly changes compared with baseline and the test group showed higher increase (p < 0.01). No statistically significant difference were found in GH, BT, BH and all clinical parameters between two groups at t1 (p > 0.05).

Conclusions

Within the limitation of this study, gingival thickness could be increased by using CGF in PAOO for the patients with thin gingival phenotype.

Trial registration The study was registered in Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) under the number ChiCTRINR17013346, Registered 11 November 2017.
Accelerated discovery of novel glycoside hydrolases using targeted functional profiling and selective pressure on the rumen microbiome
Authors: Neves André L. A. , Yu Jiangkun , Suzuki Yutaka , Baez-Magana Marisol , Arutyunova Elena , O’Hara Eóin , McAllister Tim , Ominski Kim H. , Lemieux M. Joanne , Guan Le Luo
Published: November 2021

Background

Carbohydrate-active enzymes (CAZymes) form the most widespread and structurally diverse set of enzymes involved in the breakdown, biosynthesis, or modification of lignocellulose that can be found in living organisms. However, the structural diversity of CAZymes has rendered the targeted discovery of novel enzymes extremely challenging, as these proteins catalyze many different chemical reactions and are sourced by a vast array of microbes. Consequently, many uncharacterized members of CAZyme families of interest have been overlooked by current methodologies (e.g., metagenomic screening) used to discover lignocellulolytic enzymes.

Results

In the present study, we combined phenotype-based selective pressure on the rumen microbiota with targeted functional profiling to guide the discovery of unknown CAZymes. In this study, we found 61 families of glycoside hydrolases (GH) (out of 182 CAZymes) from protein sequences deposited in the CAZy database—currently associated with more than 20,324 microbial genomes. Phenotype-based selective pressure on the rumen microbiome showed that lignocellulolytic bacteria (e.g.,Fibrobacter succinogenes, Butyrivibrio proteoclasticus) and three GH families (e.g., GH11, GH13, GH45) exhibited an increased relative abundance in the rumen of feed efficient cattle when compared to their inefficient counterparts. These results paved the way for the application of targeted functional profiling to screen members of the GH11 and GH45 families against a de novo protein reference database comprised of 1184 uncharacterized enzymes, which led to the identification of 18 putative xylanases (GH11) and three putative endoglucanases (GH45). The biochemical proof of the xylanolytic activity of the newly discovered enzyme validated the computational simulations and demonstrated the stability of the most abundant xylanase.

Conclusions

These findings contribute to the discovery of novel enzymes for the breakdown, biosynthesis, or modification of lignocellulose and demonstrate that the rumen microbiome is a source of promising enzyme candidates for the biotechnology industry. The combined approaches conceptualized in this study can be adapted to any microbial environment, provided that the targeted microbiome is easy to manipulate and facilitates enrichment for the microbes of interest.
Futures literacy in the loop
Authors: KARLSEN Jan Erik
Published: November 2021

This article proposes a functional historicist explanation to explicate the core ideas and underlying logic embedded in the futures literacy concept.

Futures literacy assumes a capacity to reflect on the past, sense and make sense of the present and use this reflective body of knowledge when anticipating the future.

Arguably, futures literacy must be learned, sustained, and regained; it requires a continuous, anticipative, and recursive loop. Recursivity, where an effect in an initial period acts as a cause in the next period, retroacts between the future and present, regaining anticipation. Anticipation has causal effects in the way it structures our images of the future and the avenue we follow when striving to achieve this image. Such a causal structure implies both feedforward and feedback control and is contained in the logic of functional explanations used in sociology.
Military archaeology and contemporary reality in Albania
Authors: Vokshi Armand , Shehu Elfrida , Dervishi Sokol
Published: November 2021

Heritage conservation provides economic, cultural and social benefits to urban communities. The building conservation role has changed from preservation to being part of a broader strategy for urban regeneration process and sustainable development. Heritage buildings are vital in for transferring the cultural identity for upcoming generations. Where heritage buildings can no longer function with its original use, proposing a new function is necessary to preserve the significance of the heritage building. This study aims to explore the fascinating dialogue between totalitarian regimes introduced in two museums adapted within the anti-nuclear bunkers in Tirana. The architectural projects of the museum aim to preserve the identity of their interior. While the careful architectural intervention is necessary to create the atmosphere of totalitarian ideology, in many cases we have to do with the continuity of existing architectural and urban elements in these particular projects. The work explores two museums, BuncArt 1 and BunkArt 2, quite interesting reflection of the parts of history, during the years of world wars and the period of dictatorship of communism, with the facilities and elements exhibited there. In the meantime, thereafter, one can speak of a longer period for the period of the communist regime extending from 1945 to 1990. The impact of communist ideology, coming from the communist bloc of the East, also affects architecture and urban studies in Albania. In some respects, we have a silent follow-up to the monumental interventions that were made before the end of World War II. Another important element was the radical intervention in the bunkers in the territory and in the cities. Their quantity is considered with an amount of 700 thousand pieces. They were different in size and were seen more as defence-related parts rather than as a direct link to the new realist-socialist architecture. The return of some of them to the exhibition space was a good step to revitalize them. Currently they have been transformed into successful tourist attractions. Visitors come to perceive three important elements: (1) attractive military engineering, carried out in contrast to the challenges of the time, (2) the suffocating atmosphere during the communist dictatorship, which required extreme safeguards, (3) elements and historical facts of the World War period, as important elements during the Cold War. An ambitious third project, which is expected to be implemented in the future, is the conversion of the Pashaliman Naval Base in Vlora into another important military museum. This port was originally set up by mid-Fifties, by Russian troops, to have control over the Adriatic. The port is currently part of the military, thought to turn into a strong tourist pole.
MCMC inversion of the transient and steady-state creep flow law parameters of dunite under dry and wet conditions
Authors: Masuti Sagar , Barbot Sylvain
Published: November 2021

The rheology of the upper mantle impacts a variety of geodynamic processes, including postseismic deformation following great earthquakes and post-glacial rebound. The deformation of upper mantle rocks is controlled by the rheology of olivine, the most abundant upper mantle mineral. The mechanical properties of olivine at steady state are well constrained. However, the physical mechanism underlying transient creep, an evolutionary, hardening phase converging to steady state asymptotically, is still poorly understood. Here, we constrain a constitutive framework that captures transient creep and steady state creep consistently using the mechanical data from laboratory experiments on natural dunites containing at least 94% olivine under both hydrous and anhydrous conditions. The constitutive framework represents a Burgers assembly with a thermally activated nonlinear stress-versus-strain-rate relationship for the dashpots. Work hardening is obtained by the evolution of a state variable that represents internal stress. We determine the flow law parameters for dunites using a Markov chain Monte Carlo method. We find the activation energy$$430\pm 20$$430±20  and$$250\pm 10$$250±10 kJ/mol for dry and wet conditions, respectively, and the stress exponent$$2.0\pm 0.1$$2.0±0.1for both the dry and wet cases for transient creep, consistently lower than those of steady-state creep, suggesting a separate physical mechanism. For wet dunites in the grain-boundary sliding regime, the grain-size dependence is similar for transient creep and steady-state creep. The lower activation energy of transient creep could be due to a higher jog density of the corresponding soft-slip system. More experimental data are required to estimate the activation volume and water content exponent of transient creep. The constitutive relation used and its associated flow law parameters provide useful constraints for geodynamics applications.

Graphical Abstract
Prioritizing zoonotic diseases using a multisectoral, One Health approach for The Economic Community of West African States (ECOWAS)
Authors: Goryoka Grace W. , Lokossou Virgil Kuassi , Varela Kate , Oussayef Nadia , Kofi Bernard , Iwar Vivian , Behravesh Casey Barton
Published: November 2021

Background

Zoonotic diseases pose a significant threat to human, animal, and environmental health. The Economic Community of West African States (ECOWAS) has endured a significant burden of zoonotic disease impacts. To address zoonotic disease threats in ECOWAS, a One Health Zoonotic Disease Prioritization (OHZDP) was conducted over five days in December 2018 to prioritize zoonotic diseases of greatest regional concern and develop next steps for addressing these priority zoonoses through a regional, multisectoral, One Health approach.

Methods

The OHZDP Process uses a mixed methods prioritization process developed by the United States Centers for Disease Control and Prevention. During the OHZDP workshop, representatives from human, animal, and environmental health ministries from all 15 ECOWAS Member States used a transparent and equal process to prioritize endemic and emerging zoonotic diseases of greatest regional concern that should be jointly addressed by One Health ministries and other partners. After the priority zoonotic diseases were identified, participants discussed recommendations and further regional actions to address the priority zoonoses and advance One Health in the region.

Results

ECOWAS Member States agreed upon a list of seven priority zoonotic diseases for the region – Anthrax, Rabies, Ebola and other viral hemorrhagic fevers (for example, Marburg fever, Lassa fever, Rift Valley fever, Crimean-Congo Hemorrhagic fever), zoonotic influenzas, zoonotic tuberculosis, Trypanosomiasis, and Yellow fever. Participants developed recommendations and further regional actions that could be taken, using a One Health approach to address the priority zoonotic diseases in thematic areas including One Health collaboration and coordination, surveillance and laboratory, response and preparedness, prevention and control, workforce development, and research.

Conclusions

ECOWAS was the first region to use the OHZDP Process to prioritize zoonotic disease of greatest concern. With identified priority zoonotic diseases for the region, ECOWAS Member States can collaborate more effectively to address zoonotic diseases threats across the region using a One Health approach. Strengthening national and regional level multisectoral, One Health Coordination Mechanisms will allow ECOWAS Member States to advance One Health and have the biggest impact on improving health outcomes for both people and animals living in a shared environment.
Potential relation between non-alcoholic fatty liver disease and glycemic and metabolic parameters in subjects without diabetes
Authors: Naguib H. , Kassab H.
Published: November 2021

Background

Nonalcoholic fatty liver disease (NAFLD) is proved to be related to insulin resistance and type 2 diabetes, and it is also not rare in individuals without diabetes. The present study attempts to identify the metabolic risk factors of NAFLD among those individuals.

Results

ALT and HbA1c levels were independently associated with NAFLD development in individuals without diabetes. Receiver operating characteristic (ROC) analysis identified the optimal cutoff point of ALT (> 19 IU/ml) with AUC = 0.731, 95% CI 0.653–0.809. On the other hand, the optimal cutoff point of HbA1c was identified to be > 5.1% with AUC = 0.665, 95% CI 0.581–0.750.

Conclusions

Early identification of NAFLD among subjects without diabetes is crucial. In this study, ALT and HbA1c cutoff values had been identified, so we suggest that inclusion of both HbA1c and ALT levels may have significant implications for prediction of NAFLD among individuals without diabetes.
Novel biomarkers assist in detection of liver fibrosis in HCV patients
Authors: Addissouky Tamer A. , Wang Yuliang , Megahed Fayed Attia Koutb , El Agroudy Ayman E. , El Sayed Ibrahim El Tantawy , El-Torgoman Abdel Moneim A. K.
Published: November 2021

Background

Accurate staging in individuals infected with hepatitis C is imperative to understand their long-term risk for liver-related complications. Liver biopsy has a traditional role to determine the levels of liver fibrosis specifically in hepatitis C virus patients. However, the development of non-invasive options has reduced the utilization of biopsy in this population.

Main body of the abstract

Detecting fibrosis levels through blood samples is already an acceptable alternative to biopsy; however, the optimal non-invasive panel has yet to be defined. Our study indicated hyaluronic acid, collagen oligomeric matrix protein, collagen type IV, and liver fibrosis scoring systems to distinguish fibrosis patients from the non-fibrosis group.

Short conclusion

The combination of these novel biomarkers, H. A, CO-IV, and Comp tests, could be used to accurately stage individuals with hepatitis C.