bluuebunny/crossref_metadata_2025 huggingface dataset:
SS-31 Modification Inhibits the Proinflammatory Effect on Macrophages Induced by Superparamagnetic Iron Oxide Nanoparticles
Authors: Lu Qizheng , Liu Haibo , Zheng Hao , Zhang Youming , Ou Jinbo , You Jieyun , Zhang Qi , Pi Jingjiang , Yao Xiaobo , Xu Jing , Wang Xingxu , Wang Yunkai , Pei Ning , Shen Yunli
Published: September 2022

Superparamagnetic iron oxide nanoparticles can induce macrophage polarization into the proinflammatory M1-type. This adverse effect is very likely to restrict the applications of superparamagnetic iron oxide nanoparticles in various inflammatory medical conditions. To inhibit the proinflammatory
effect, the mitochondrial-targeted antioxidant peptide SS-31 was physically adsorbed on superparamagnetic iron oxide nanoparticles to develop superparamagnetic iron oxide nanoparticles@SS-31. The macrophages (RAW 264.7) were incubated with superparamagnetic iron oxide nanoparticles or superparamagnetic
iron oxide nanoparticles@SS-31 at a concentration of 50 μg Fe3O4/mL for 24 hours. Compared to the superparamagnetic iron oxide nanoparticles group, the superparamagnetic iron oxide nanoparticles@SS-31 group demonstrated significantly reduced cell damage, as
evidenced by the inhibition of cell viability loss, early cell apoptosis and the production of reactive oxygen species. Moreover, the proinflammatory factor TNF-α and M1-type cell surface markers CD86 and CD80 were significantly downregulated in the superparamagnetic iron oxide
nanoparticles@SS-31 group as shown by enzyme-linked immunosorbent assay and flow cytometric analysis. Notably, compared with the superparamagnetic iron oxide nanoparticles group, levels of the anti-inflammatory factors IL-10, TGF-β and the M2-type cell surface marker CD163 were
markedly upregulated in the superparamagnetic iron oxide nanoparticles@SS-31 group. In addition, severe disruption of the mitochondrial ultrastructure was observed by transmission electron microscopy in the superparamagnetic iron oxide nanoparticles group, but the superparamagnetic iron oxide
nanoparticles@SS-31 group displayed structurally intact mitochondria. All of these results suggest that superparamagnetic iron oxide nanoparticles can promote macrophage M1-type polarization by inducing oxidative stress and mitochondrial damage, while superparamagnetic iron oxide nanoparticles@SS-31
can significantly inhibit superparamagnetic iron oxide nanoparticles-induced toxicity by releasing SS-31 to exert mitochondrial-targeted antioxidant and anti-inflammatory effects, indicating that the strategy of coloading the SS-31 peptide into superparamagnetic iron oxide nanoparticles has
the potential to alleviate superparamagnetic iron oxide nanoparticles-induced proinflammatory effects.
Low-Level Cloud Budgets across Sea Ice Edges
Authors: Zheng Youtong , Ming Yi
Published: September 2022

Interpreting behaviors of low-level clouds (LLCs) in a climate model is often not straightforward. This is particularly so over polar oceans where frozen and unfrozen surfaces coexist, with horizontal winds streaming across them, shaping LLCs. To add clarity to this interpretation issue, we conduct budget analyses of LLCs using a global atmosphere model with a fully prognostic cloud scheme. After substantiating the model’s skill in reproducing observed LLCs, we use the modeled budgets of cloud fraction and water content to elucidate physics governing changes of LLCs across sea ice edges. Contrasting LLC regimes between open water and sea ice are found. LLCs over sea ice are primarily maintained by large-scale condensation: intermittent intrusions of maritime humid air and surface radiative cooling jointly sustain high relative humidity near the surface, forming extensive but tenuous stratus. This contrasts with the LLCs over open water where the convection and boundary layer condensation sustain the LLCs on top of deeper boundary layers. Such contrasting LLC regimes are influenced by the direction of horizontal advection. During on-ice flow, large-scale condensation dominates the regions, both open water and sea ice regions, forming clouds throughout the lowest several kilometers of the troposphere. During off-ice flow, as cold air masses travel over the open water, the cloud layer lifts and becomes denser, driven by increased surface fluxes that generate LLCs through boundary layer condensation and convective detrainment. These results hold in all seasons except summer when the atmosphere–surface decoupling substantially reduces the footprints of surface type changes.
The effects of β-catenin on cardiomyogenesis via Islet-1 and MLIP ubiquitination
Authors: Yan Liang , Xie Min , Tan Bin , Xu Hao , Yi Qin , Ye Liang , Zhang Xinyuan , Zhang Yin , Tian Jie , Zhu Jing
Published: September 2022

Mesenchymal stem cells (MSCs) can treat myocardial injury–related diseases by differentiating into cardiomyocytes. Islet-1 plays an essential role in cardiac maturation. We have discovered that Islet-1 plays a crucial role in the histone acetylation regulation in this process. In addition, to increase GATA4/Nkx2.5 expression, Islet-1 may bind to Gcn5 and then guide Gcn5 to the GATA4/Nkx2.5 promoters, thereby facilitating the differentiation of MSCs into cardiomyocytes. Islet-1 is an important factor in the maturation of the heart. We have previously found that the pivotal factor in histone acetylation regulation in this process is Islet-1. Furthermore, Islet-1 and Gcn5 may boost GATA4/Nkx2.5 expression, which in turn promotes cardiomyocyte differentiation from MSCs. But the molecular mechanism of Islet-1 binding to GCN5 has not been elucidated. In this study, we found that the competitive binding relationship between Islet-1 and MLIP and GCN5 affected myocardial differentiation. The key enzymes of ubiquitination modification of MLIP and Islet-1 are UBE3C and WWP1, respectively. When short hairpin RNA (shRNA) was used to inhibit β-catenin expression, we found that the expression of UBE3C was upregulated, modifying MLIP ubiquitination and reducing its expression, and it upregulated Islet-1 by inhibiting the expression of WWP1. By using the chromatin immunoprecipitation (ChIP) and luciferase reporter system, we found that when MLIP binds to Islet-1, it significantly inhibits the transcriptional activity of Islet-1. In summary, our results show that decreasing β-catenin regulates the ubiquitination of Islet-1 and MLIP, affecting their expression, reducing the amount of Islet-1 binding to MLIP, and increasing the amount of binding to GCN5 in the nucleus. Therefore, the transcriptional activity of Islet-1 is significantly activated, inducing C3H10T1/2 cells to differentiate into myocytes. Further knowledge of biochemical pathways, including molecular signaling pathways, can provide more insights into the myocardial differentiation mechanism of MSCs.
Assessment of the influence on left ventricle by potassium oxonate and hypoxanthine–induced chronic hyperuricemia
Authors: Lin Cuiting , Zheng Qiang , Li Yongmei , Wu Ting , Luo Jian , Jiang Yanqing , Huang Qinghua , Yan Caixin , Zhang Leqi , Zhang Wei , Liao Hui , Yang Yang , Pang Jianxin
Published: September 2022

Cellular cytoplasmic xanthine oxidase (XO)–mediated uric acid synthesis and extracellular excess uric acid exposure are both causes of cardiomyocytic injury under the condition of hyperuricemia (HUA). Potassium oxonate suppresses uric acid degradation to increase extracellular concentration, while hypoxanthine is the catalytic substrate of XO. We aimed to observe cardiac damage in a chronic HUA mouse model induced by potassium oxonate and hypoxanthine. The mouse model was established by the co-administration of potassium oxonate and hypoxanthine for eight weeks. Then, left ventricular parameters were examined by echocardiographic evaluation, and the heart tissues were harvested for further histopathological analysis. The results showed that plasma uric acid was persistently elevated in the model mice, which demonstrated the stable establishment of chronic HUA. The left ventricular anterior wall was significantly thickened in the model group compared with the blank control group. After the end of modeling, the left ventricular anterior wall thickness of the hyperuricemic mice increased compared with that of blank group. The histological analysis showed and myocardial structure disorganization in the model group compared with the blank control. The above cardiac impairment changes could be attenuated by allopurinol pretreatment. This study systematically assessed cardiac damage in a chronic HUA mouse model. In addition, it provides useful information for future HUA-associated heart injury mechanism investigation and therapeutic treatment evaluation.
Long-term prognosis of curative endoscopic submucosal dissection for early colorectal cancer according to submucosal invasion: a multicenter cohort study
Authors: Shin Jongbeom , Kim Eun Ran , Jang Hyun Joo , Baek Dong Hoon , Yang Dong-Hoon , Lee Bo-In , Cho Kwang Bum , Cho Jin Woong , Jung Sung-Ae , Hong Su Jin , Ko Bong Min ,   The Research Group for Endoscopic Submucosal Dissection in Korean Society of Gastrointestinal Endoscopy, Jeon Jung-Won , Ko Weon Jin , Kim Sun Moon , Kim Young Dae , Gyoo Kim Chan , Baik Gwang Ho , Yoo In Kyung , Nyeong Lee Kang , Lee Si Hyung , Lim Chul-Hyun , Jeon Seong Woo
Published: September 2022

Background

Endoscopic submucosal dissection (ESD) can provide a high en bloc resection rate and has been widely applied as curative treatment for early colorectal cancer (ECC). However, surgical treatment is occasionally required, and reports on the long-term prognosis of ESD are insufficient. This study aimed to investigate the long-term outcomes of ECC removal by ESD, including local recurrence and metastasis.

Methods

This multicenter study was conducted retrospectively on 450 consecutive patients with ECC who were treated with ESD between November 2003 and December 2013. Clinical, pathological, and endoscopic data were collected to determine tumor depth, resection margin, lymphovascular invasion, and recurrence.

Results

The median follow-up period was 53.8 (12–138 months). The en bloc resection rate was 85.3% (384) and in intramucosal cancer being 84.1% and in superficial submucosal invasion (SM1) cancer being 89.8% (p = 0.158). The curative resection rate was 76.0% (n = 342), and there was no statistical difference between the two groups (77.3% vs. 71.4%, p = 0.231). The overall recurrence free survival rate (RFS) was 98.7% (444/450). In patients with curative resection, there was no statistically significant difference in RFS according to invasion depth (intramucosal: 99.3% vs. SM1: 97.1%, p = 0.248).

Conclusions

Patients with curatively resected ECC treated with ESD showed favorable long-term outcomes. Curatively resected SM1 cancer has a RFS similar to that of intramucosal cancer.
Analysis of patient’s X-ray exposure in hepatic chemosaturation procedures: a single center experience
Authors: Ebel Sebastian , Reinhardt Martin , Beeskow Anne Bettina , Teske Felix , Struck Manuel Florian , Veelken Rhea , van Boemmel Florian , Berg Thomas , Moche Michael , Gutberlet Matthias , Gößmann Holger , Denecke Timm
Published: September 2022

Background

Hepatic chemosaturation is a technique in which a high dose of the chemotherapeutic agent melphalan is administered directly into the liver while limiting systemic side effects. We reviewed our institutional experience regarding patient’s X-ray exposure caused by the procedure.

Methods

Fifty-five procedures, performed between 2016 and 2020 in 18 patients by three interventional radiologists (radiologist), were analyzed regarding the patient’s exposure to radiation. Dose-area-product (DAP) and fluoroscopy time (FT) were correlated with the experience of the radiologist and whether the preprocedural evaluation (CS-EVA) and the procedure were performed by the same radiologist. Additionally, the impact of previous liver surgery on DAP/FT was analyzed.

Results

Experienced radiologist require less DAP/FT (50 ± 18 Gy*cm2/13.2 ± 3.84 min vs. 69 ± 20 Gy*cm2/15.77 ± 7.82 min; p < 0.001). Chemosaturations performed by the same radiologist who performed CS-EVA required less DAP/FT (41 ± 12 Gy*cm2/11.46 ± 4.41 min vs. 62 ± 11 Gy*cm2/15.55 ± 7.91 min; p < 0.001). Chemosaturations in patients with prior liver surgery with involvement of the inferior cava vein required significantly higher DAP/FT (153 ± 27 Gy*cm2/25.43 ± 4.57 min vs. 56 ± 25 Gy*cm2/14.44 ± 7.55 min; p < 0.001).

Conclusion

There is a significant learning curve regarding the procedure of hepatic chemosaturation. Due to dose reduction the evaluation and chemosaturation therapy should be performed by the same radiologist. Procedures in patients with previous liver surgery require higher DAP/FT.
Immune checkpoint inhibitor (ICI) genes and aging in malignant melanoma patients: a clinicogenomic TCGA study
Authors: Safi Mohammed , Jin Chenxing , Aldanakh Abdullah , Feng Ping , Qin Henan , Alradhi Mohammed , Zhang Lizhi , Zhang Junying , Adlat Salah , Zhao Yi , Liu Jiwei
Published: September 2022

Background

Cancer diagnoses and deaths among the elderly (65 +) are expected to increase significantly over the next decade. Immune checkpoint inhibitors specifically target ICI genes and enhance immune system function. However, poor outcomes may be associated with aging.

Methods

We downloaded the Genomic Data Commons from the Cancer Genome Atlas (TCGA) and collected gene expression data from malignant melanoma (MM) tissues, the third level as the primary site. The CKTTD ICI genes database were applied and validated using the GEO database and lab experiments.

Results

In 414 patients, 13 ICI genes were obtained as risk gene signature by univariate and multivariate Cox hazard models and were associated with poor survival in the older group. At 1, 3, and 5 years (79%, 76%, and 76%, respectively), we investigate TNFRFS4 gene and age prediction using novel nomogram-associated aging (HR = 1.79, P 0.001, CI = 1.32–2.45) with higher sensitivity testing.TNFRSF4 gene expression was significantly high in younger (15 years interval) MM patients (P < 0.001). By correlation analysis, a significant negative association was determined (P < 0.001). The validation of gene correlation from GEO (GSE59455) and (GSE22153) was obtained as external validation. We tested the TNFRSF4 protein levels by IHC in 14 melanoma tissue samples. TNFRSF4 expression was observed to be lower expressed in the older of melanoma tissues, and higher in the younger age group (P = 0.02). Besides the connectivity of ICI gene proteins, the biological processes of cell aging, aging, and the immune system were found to be highly related.

Conclusions

Along with the risk score evaluation, the ICI gene (TNFRSF4) was identified as a tumor suppressor gene related to inequalities in age survival and associated with immune cell infiltrations. The aging responses of melanoma patients and related gene expression need further investigation in order to identify potential therapeutic targets.
Programmed cell death ligand 1 measurement study in granulocyte colony-stimulating factor-producing lung cancer: an observational study
Authors: Miyazaki Kazuhito , Shiba Aya , Ikeda Toshiki , Higashi Yuko , Aga Masaharu , Hamakawa Yusuke , Taniguchi Yuri , Misumi Yuki , Agemi Yoko , Nakamura Yukiko , Shimokawa Tsuneo , Okamoto Hiroaki
Published: September 2022

Background

Granulocyte colony-stimulating factor (G-CSF)-producing lung cancer induces severe inflammation and a high white blood cell (WBC) count and is associated with poor prognosis. A recent case of G-CSF-producing lung adenocarcinoma showed high expression of programmed cell death ligand 1 (PD-L1) and was treated with pembrolizumab as first-line therapy, which was extremely effective. We hypothesized that G-CSF-producing lung cancers are associated with high PD-L1 expression.

Methods

This retrospective study included patients diagnosed with lung cancer at Yokohama Municipal Citizen’s Hospital (Kanagawa, Japan) between 2009 and 2019. The PD-L1 status of 13 patients with high plasma G-CSF levels (≥40 pg/mL) was assessed by conducting immunohistochemical analysis of tissue samples.

Results

Of the total patients, 11 were men and 2 were women, with a median age of 74 years (70–85 years). Four, five, and three patients had adenocarcinoma, squamous cell carcinoma, and others, respectively. The median G-CSF level and WBC count were 85.5 pg/mL (range, 40.8–484 pg/mL) and 15,550/μL (range, 6,190–56,800/μL), respectively. The PD-L1 tumor proportion scores (TPSs) were ≥50%, 1%–49%, and <1% in 9, 1, and 3 patients, respectively. The median overall survival time was 7.3 months. Pembrolizumab was administered in six patients as first-line treatment, with two patients showing partial response, one patient with stable disease, and three patients with progressive disease. All six patients had a PD-L1 TPS of ≥50%.

Conclusion

G-CSF-producing lung cancers may be associated with increased PD-L1 expression. Although immune checkpoint inhibitors are an important treatment option for G-CSF-producing tumors, their effects are limited.
Physical activity and quality of life in children with idiopathic toe walking: a cross sectional study
Authors: Caserta Antoni , Reedman Sarah , Morgan Prue , Williams Cylie M.
Published: September 2022

Objectives

To determine if children with idiopathic toe walking (ITW) reach Australian 24-hour movement guidelines. Additional objectives were to identify any factors associated with moderate to vigorous physical activity time of children with ITW.

Design

Cross sectional.

Setting

Private practice, public health outpatient, community clinics.

Participants

Children between 4 and 14 years, who toe walked and had no medical conditions known to cause ITW.

Outcome measures

Physical activity intensity, sedentary behaviour and sleep data were collected via an ActiGraph. Physical activity level intensity data were triangulated with the Child Leisure Activities Study Survey (CLASS) to highlight the subjective nature of parent-reported measures. Health related quality of life information was collected using the Parent-Proxy and Child-Self Report Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scale. Regression analyses were used to explore individual factors associated with moderate to vigorous physical activity.

Results

Twenty-seven participants, 17(63%) male, age mean = 6.62 (SD = 2.29) years, provided information on physical activity (CLASS n = 18, ActiGraph n = 22), physical functioning and psychosocial functioning domains on the PedsQL (Parent-Proxy n = 25, Child n = 22). All participants exceeded Australian recommendations for physical activity, 44% (8/18) met recommended screen time amounts, and two (9%) met recommended sleep times. The Child-Self Report PedsQL scale score of social functioning was the only factor associated with an increase in physical activity (Coef = 0.48, 95%CI = 0.09 to 0.87, p = 0.019).

Conclusion

Participants achieved high levels of daily moderate to vigorous physical activity, and this was associated with social functioning. Given current uncertainty regarding benefits and effectiveness of treatment choices for children who have ITW, these findings should encourage clinicians to consider how their treatment recommendations interact with the PA level and sleep of children with ITW. Any treatment choice should also be implemented with consideration of how it may impact social functioning. This study had a small sample size therefore results should be cautiously interpreted and not generalised to all children with ITW.
“We’re all going through it”: impact of an online group coaching program for medical trainees: a qualitative analysis
Authors: Mann Adrienne , Fainstad Tyra , Shah Pari , Dieujuste Nathalie , Thurmon Kerri , Dunbar Kimiko , Jones Christine
Published: September 2022

Background

Trainees in graduate medical education are affected by burnout at disproportionate rates. Trainees experience tremendous growth in clinical skills and reasoning, however little time is dedicated to metacognition to process their experiences or deliberate identity formation to create individualized definitions of success and wellbeing. The purpose of this study was to understand the perspectives and experiences of trainees who participated in a 6-month, web-based, group coaching program for women residents in training.

Methods

Better Together Physician Coaching is a six-month, self-paced, online, asynchronous, coaching program with multiple components including live coaching calls, unlimited written coaching, and self-study modules. Semi-structured interviews of seventeen participants of Better Together from twelve GME programs within a single institution in Colorado were conducted from May to June of 2021. All identified as women and had participated in a 6-month coaching program. Both inductive and deductive methods were used in collecting and analyzing the data with an aim to understand learners’ perceptions of the coaching program, including “how and why” the coaching program affected training experiences and wellbeing.

Results

Three main themes emerged as benefits to the coaching program from the data: 1) practicing metacognition as a tool for healthy coping 2) building a sense of community, and 3) the value of a customizable experience.

Conclusions

Female trainees who participated in a group coaching program expressed that they found value in learning how to cope with stressors through metacognition-focused coaching. They also described that building a community and being able to customize the experience were positive aspects of the program.

Trial registration

ClinicalTrials.gov Identifier: NCT05280964. Date of registration: March 15th 2022. Retrospectively registered. URL of trial registry record.
Perceived barriers and enablers influencing health extension workers toward home-based hypertension screening in rural northwest Ethiopia: interpretive descriptive study
Authors: Teshome Destaw Fetene , Balcha Shitaye Alemu , Ayele Tadesse Awoke , Atnafu Asmamaw , Sisay Mekonnen , Asfaw Marye Getnet , Mitike Getnet , Gelaye Kassahun Alemu
Published: September 2022

Background

Hypertension, a major but modifiable risk factor for cardiovascular diseases, is a global health problem including Ethiopia. In a limited infrastructure task sharing of hypertension screening for community health workers is a feasible strategy to improve hypertension management. Recent finding have shown that trained health extension workers (HEWs) can identify high blood pressure, which was effective and feasible. Identifying barriers and enablers for home-based hypertension screening by HEWs is crucial for its implementation. This study aimed to explore barriers and enablers that influence health extension workers’ home-based hypertension screening in the community.

Methods

The interpretive descriptive design was implemented. In-depth interviews were conducted during October, 2020. A total of 26 participants including HEWs, supervisors, and heads of district health office were purposively selected. They were asked to describe their perception toward home-based hypertension screening by the HEWs. The interviews were audio-recorded, transcribed verbatim into Amharic, and translated into English. The transcripts were coded and themes were identified. Thematic approach was used for data analysis.

Results

The participants identified key perceived barriers and enablers of HEWs home-based hypertension screening. The most common barriers were a lack of hypertension training, blood pressure measuring devices, blood pressure guidelines and manuals, skilled HEWs, financial incentives, and poor community awareness of the disease. The most common enablers were support from community leaders, presence of functional development army and community trust for HEWs, presence of routine campaign on vaccination and community based health insurance, and an integrated health system.

Conclusions

Our findings have implications for the HEWs' ongoing implementation of home-based hypertension screening. Successful implementation of this strategy requires scaling up of hypertension training programs for health extension workers and their supervisors, provision of standardized protocols, provision of adequate blood pressure measuring equipment, and regular supportive supervision.
miR-1908: a microRNA with diverse functions in cancers and non-malignant conditions
Authors: Ghafouri-Fard Soudeh , Khoshbakht Tayyebeh , Hussen Bashdar Mahmud , Taheri Mohammad , Samsami Majid
Published: September 2022

MicroRNAs (miRNAs) are small-sized transcripts with about 22 nucleotide length. They have been shown to influence almost every aspect of cellular functions through regulation of expression of target genes. miR-1908 is a miRNA with diverse roles in human disorders. This miRNA is encoded by MIR1908 gene on chr11:61,815,161–61,815,240, minus strand. Expression assays have confirmed dysregulation of miR-1908 in cancer-derived cell lines in addition to biological samples obtained from patients affected with cancer. In most assessed cell lines, miR-1908 has an oncogenic role. However, this miRNA has been shown to act as a tumor suppressor in chordoma, lung cancer and ovarian cancer. In addition, several lines of evidence have shown involvement of this miRNA in the pathoetiology of bipolar disorder, myocardial infarction, obesity, renal fibrosis, rheumatoid arthritis and scar formation. In the current review, we elucidate the results of diverse studies which evaluated participation of miR-1908 in these conditions.
Streamlining sporozoite isolation from mosquitoes by leveraging the dynamics of migration to the salivary glands
Authors: Pathak Ashutosh K. , Shiau Justine C. , Franke-Fayard Blandine , Shollenberger Lisa M. , Harn Donald A. , Kyle Dennis E. , Murdock Courtney C.
Published: September 2022

Background

Sporozoites isolated from the salivary glands ofPlasmodium-infected mosquitoes are a prerequisite for several basic and pre-clinical applications. Although salivary glands are pooled to maximize sporozoite recovery, insufficient yields pose logistical and analytical hurdles; thus, predicting yields prior to isolation would be valuable. Preceding oocyst densities in the midgut is an obvious candidate. However, it is unclear whether current understanding of its relationship with sporozoite densities can be used to maximize yields, or whether it can capture the potential density-dependence in rates of sporozoite invasion of the salivary glands.

Methods

This study presents a retrospective analysis ofAnopheles stephensimosquitoes infected with two strains of the rodent-specificPlasmodium berghei.Mean oocyst densities were estimated in the midguts earlier in the infection (11–15 days post-blood meal), with sporozoites pooled from the salivary glands later in the infection (17–29 days). Generalized linear mixed effects models were used to determine if (1) mean oocyst densities can predict sporozoite yields from pooled salivary glands, (2) whether these densities can capture differences in rates of sporozoite invasion of salivary glands, and (3), if the interaction between oocyst densities and time could be leveraged to boost overall yields.

Results

The non-linear effect of mean oocyst densities confirmed the role of density-dependent constraints in limiting yields beyond certain oocyst densities. Irrespective of oocyst densities however, the continued invasion of salivary glands by the sporozoites boosted recoveries over time (17–29 days post-blood meal) for either parasite strain.

Conclusions

Sporozoite invasion of the salivary glands over time can be leveraged to maximize yields forP. berghei. In general, however, invasion of the salivary glands over time is a critical fitness determinant for allPlasmodiumspecies (extrinsic incubation period, EIP). Thus, delaying sporozoite collection could, in principle, substantially reduce dissection effort for any parasite within the genus, with the results also alluding to the potential for changes in sporozoites densities over time to modify infectivity for the next host.
Health Inequality Monitoring channel on OpenWHO: capacity strengthening through eLearning
Authors: Bergen Nicole , Kirkby Katherine , Baptista Andreia , Nambiar Devaki , Schlotheuber Anne , Vidal Fuertes Cecilia , Hosseinpoor Ahmad Reza
Published: September 2022

Background

Health inequality monitoring can generate important evidence to inform and motivate changes to policy, programmes and practices. However, the potential of health inequality monitoring practices to quantify inequalities between population subgroups and track progress on the advancement of health equity is under-realized. Capacity strengthening on health inequality monitoring can play an important role in enhancing political will for the generation and use of disaggregated data and for wider adoption of this practice to inform health decision-making. There is a lack of widely available and accessible training materials related to health inequality monitoring that may be used by a range of stakeholders.

Objective

In this paper, we describe the design, development and implementation of the Health Inequality Monitoring channel on the OpenWHO eLearning platform. We discuss the anticipated impact and potential opportunities for these eLearning courses to contribute to strengthened health inequality monitoring practices.

Results

The Health Inequality Monitoring channel on the OpenWHO platform is a self-directed learning environment, designed to meet the immediate learning needs of users. The channel contains three series of courses: health inequality monitoring foundations courses; topic-specific health inequality monitoring courses; and health inequality monitoring skill building courses. Courses are primarily targeted to monitoring and evaluation officers, data analysts, academics and researchers, public health professionals, medical and public health students, and others with a general interest in health data and inequality monitoring.

Conclusions

WHO eLearning courses on health inequality monitoring are addressing the need for capacity strengthening in the collection, analysis and reporting of inequality data. They introduce learners to the foundational concepts, best practices, tools and skills required to conduct health inequality monitoring. The courses on the Health Inequality Monitoring channel demonstrate how technical information can be simplified and presented to broad audiences in a manner that is highly accessible to learners. The Health Inequality Monitoring channel on OpenWHO is an innovative and necessary addition to existing tools and resources to support the advancement of health equity.
SARS-CoV-2 omicron variant clearance delayed in breakthrough cases with elevated fasting blood glucose
Authors: Zhang Xiujun , Si Guocan , Lu Huifen , Zhang Wei , Zheng Shuqin , Huang Zeyu , Liu Longgen , Xue Yuan , Zheng Guojun
Published: September 2022

Background

Omicron variant (B.1.1.529) is a dominant variant worldwide. However, the risk factors for Omicron variant clearance are yet unknown. The present study aimed to investigate the risk factors for early viral clearance of Omicron variant in patients with a history of inactivated vaccine injection.

Methods

Demographic, clinical, and epidemiological data from 187 patients were collected retrospectively during the Omicron variant wave.

Results

73/187 and 114/187 patients were administered two and three doses of vaccine, respectively. The median duration of SARS-CoV-2 RNA positivity was 9 days, and the difference between patients with two and three vaccine injections was insignificant (P = 0.722). Fever was the most common symptom (125/187), and most patients (98.4%) had a fever for < 7 days. The RNA was undetectable in 65/187 patients on day 7. Univariable logistic analysis showed that baseline glucose, uric acid, lymphocytes count, platelet count, and CD4+ T lymphocyte count were associated with SARS-CoV-2 RNA-positivity on day 7. Multivariable analysis showed that glucose ≥ 6.1 mmol/L and CD4+T lymphocytes count were independent risk factors for RNA positivity on day 7. 163/187 patients had an undetectable RNA test on day 14, and uric acid was the only independent risk factor for RNA positivity. Moreover, baseline glucose was negatively correlated with uric acid and CD4+ and CD8+ T cell count, while uric acid was positively correlated with CD4+ and CD8+ T cell count.

Conclusions

Omicron variant clearance was delayed in breakthrough cases with elevated fasting blood glucose, irrespective of the doses of inactivated vaccine.
Utility of viscoelastic hemostatic assay to guide hemostatic resuscitation in trauma patients: a systematic review
Authors: Zhu Zhe , Yu Yong , Hong Kairui , Luo Mengqin , Ke Yefang
Published: September 2022

Objective

Viscoelastic hemostatic assay (VHA) provides a graphical representation of a clot’s lifespan and reflects the real time of coagulation. It has been used to guide trauma resuscitation; however, evidence of the effectiveness of VHAs is still limited. This systematic review aims to summarize the published evidence to evaluate the VHA-guided strategy in resuscitating trauma patients.

Methods

The PubMed, Embase, and Web of Science databases were searched from their inception to December 13, 2021. Randomized controlled trials (RCTs) or observational studies comparing VHA-guided transfusion to controls in resuscitating trauma patients were included in this systematic review.

Results

Of the 7743 records screened, ten studies, including two RCTs and eight observational studies, met the inclusion criteria. There was great heterogeneity concerning study design, enrollment criterion, VHA device, VHA-guided strategy, and control strategy. Thrombelastography (TEG) was used as a guiding tool for transfusion in eight studies, and rotational thromboelastometry (ROTEM), and TEG or ROTEM were used in the other two studies. The overall risk of bias assessment was severe or mild in RCTs and was severe or moderate in observational studies. The main outcomes reported from the included studies were blood transfusion (n = 10), mortality (n = 10), hospital length of stay (LOS) (n = 7), intensive care unit LOS (n = 7), and cost (n = 4). The effect of the VHA-guided strategy was not always superior to the control. Most of the studies did not find significant differences in the transfusion amount of red blood cells (n = 7), plasma (n = 5), platelet (n = 7), cryoprecipitate/fibrinogen (n = 7), and mortality (n = 8) between the VHA-guided group and control group. Notable, two RCTs showed that the VHA-guided strategy was superior or equal to the conventional coagulation test-guided strategy in reducing mortality, respectively.

Conclusion

Although some studies demonstrated VHA-guided strategy probable benefit in reducing the need for blood transfusion and mortality when resuscitating trauma patients, the evidence is still not robust. The quality of evidence was primarily downgraded by the limited number of included studies and great heterogeneity and severe risk of bias in these. Further studies are strongly recommended.
Sarcoptic mange changes bacterial and fungal microbiota of bare-nosed wombats (Vombatus ursinus)
Authors: Næsborg-Nielsen Christina , Eisenhofer Raphael , Fraser Tamieka A. , Wilkinson Vicky , Burridge Christopher P. , Carver Scott
Published: September 2022

Background

Sarcoptes scabiei is globally distributed and one of the most impactful mammalian ectoparasites. Sarcoptic mange, caused by infection with S. scabiei, causes disruption of the epidermis and its bacterial microbiota, but its effects on host fungal microbiota and on the microbiota of marsupials in general have not been studied. Here, we (i) examine bacterial and fungal microbiota changes associated with mange in wild bare-nosed wombats (BNWs) and (ii) evaluate whether opportunistic pathogens are potentiated by S. scabiei infection in this species.

Methods

Using Amplicon Sequencing of the 16S rRNA and ITS2 rDNA genes, we detected skin microbiota changes of the bare-nosed wombat (Vombatus ursinus). We compared the alpha and beta diversity among healthy, moderate, and severe disease states using ANOVA and PERMANOVA with nesting. Lastly, we identified taxa that differed between disease states using analysis of composition of microbes (ANCOM) testing.

Results

We detected significant changes in the microbial communities and diversity with mange in BNWs. Severely affected BNWs had lower amplicon sequence variant (ASV) richness compared to that of healthy individuals, and the microbial communities were significantly different between disease states with higher relative abundance of potentially pathogenic microbial taxa in mange-affected BNWs including Staphylococcus sciuri, Corynebacterium spp., Brevibacterium spp., Brachybacterium spp., and Pseudogymnascus spp. and Debaryomyces spp.

Conclusion

This study represents the first investigation of microbial changes in association with sarcoptic mange in a marsupial host, as well as the first investigation of fungal microbial changes on the skin of any host suffering from sarcoptic mange. Our results are broadly consistent with bacterial microbiota changes observed in humans, pigs, canids, and Iberian ibex, suggesting the epidermal microbial impacts of mange may be generalisable across host species. We recommend that future studies investigating skin microbiota changes include both bacterial and fungal data to gain a more complete picture of the effects of sarcoptic mange.

Graphical Abstract
Analysis of gastric microbiota and Helicobacter pylori infection in gastroesophageal reflux disease
Authors: Sugihartono Titong , Fauzia Kartika Afrida , Miftahussurur Muhammad , Waskito Langgeng Agung , Rejeki Purwo Sri , I’tishom Reny , Alfaray Ricky Indra , Doohan Dalla , Amalia Rizki , Savitri Camilia Metadea Aji , Rezkitha Yudith Annisa Ayu , Akada Junko , Matsumoto Takashi , Yamaoka Yoshio
Published: September 2022

Background

We evaluated the microbiota in the stomach of Gastroesophageal Reflux Disease (GERD) patients. We compared Erosive Reflux Disease (ERD) to gastritis and Non-erosive Reflux Disease (NERD) subjects by 16S rRNA approach on gastric biopsy specimens. A total of 197 subjects were included consisting of gastritis (68; 34.52%), ERD (55; 27.92%), and NERD (74; 37.56%). After quality filtering, 187 samples were included for OTU analysis using Qiime2.

Results

We observed a significant difference in alpha diversity (Shannon and Simpson indexes were P = 0.0016 and P = 0.017, respectively). A significant decrease in alpha diversity index was observed in NERD with Helicobacter pylori (H. pylori)-positive subjects than in gastritis (Simpson index P = 0.022; Shannon index P = 0.029), indicating a significant influence of H. pylori on the diversity in the stomach despite the diseases. In H. pylori-negative samples, alpha diversity measurement by the abundance coverage estimates (ACE) and Fisher Test revealed that ERD had significantly lower richness than gastritis and NERD groups (P = 0.00012 and P = 0.00043, respectively). Anaerobacillus sp. could only be found in ERD patients by LEFse analysis.

Conclusions

The presence of ERD could alter microbiome diversity. A negative correlation between H. pylori and ERD is shown in this microbiome study but not in NERD.
Immortalised canine buccal epithelial cells’ CXCL8 secretion is affected by allergen extracts, Toll-like receptor ligands, IL-17A and calcitriol
Authors: Pelst Michael , Höbart Clara , de Rooster Hilde , Devriendt Bert , Cox Eric
Published: September 2022

Epithelial cells are known to produce mediators which can influence the behaviour of neighbouring immune cells. Although the oral mucosa has gained increased interest as a route to induce allergy desensitisation and mucosal pathogen immunisation in dogs, there is only limited knowledge on the factors which impact mediator secretion by canine oral epithelial cells. The study’s objective was to enlarge the knowledge on the stimuli that can influence the secretion of some pro- and anti-inflammatory cytokines and the chemokine CXCL8 by canine buccal epithelial cells. To investigate this, buccal epithelial cells were isolated from a biopsy of a dog and immortalised by lentiviral transduction of the SV40 large T antigen. The cells were stained with a CD49f and cytokeratin 3 antibody to confirm their epithelial origin. Cells were incubated with allergen extracts, Toll-like receptor ligands (TLRL), recombinant cytokines and vitamin A and D metabolites. Subsequently, the secretion of the cytokines interleukin (IL)-4, IL-6, IL-10, IL-17A, IFN-γ, TGF-β1 and the chemokine CXCL8 was assayed by ELISA. Immortalised canine buccal epithelial cells stained positive for CD49f but not for cytokeratin 3. The cells produced detectable amounts of CXCL8 and TGF-β1. ADermatophagoides farinaeextract, anAlternaria alternataextract, Pam3CSK4, heat-killedListeria monocytogenes, FSL-1, flagellin and canine recombinant IL-17A significantly increased CXCL8 secretion, while the vitamin D metabolite calcitriol significantly suppressed the production of this chemokine. This study showed that certain allergens, TLRL, IL-17A and calcitriol modulate CXCL8 secretion in a cell line of canine buccal epithelial cells.
The impact of maternal health insurance coverage and adequate healthcare services utilisation on the risk of under-five mortality in Nigeria: a cross-sectional study
Authors: Imo Chukwuechefulam Kingsley , De Wet-Billings Nicole , Isiugo-Abanihe Uche Charlie
Published: September 2022

Background

Despite the progress in reducing under-five mortality (U-5 M) in recent years, these deaths remain considerably high in Nigeria. This could be attributed to poor health policies including inequality of health insurance coverage and access to adequate healthcare services utilisations which has remained inimical to achieving sustainable development goals (SDGs). Therefore, this study examined the impact of maternal health insurance coverage and adequate healthcare services utilisation on the risk of U-5 M in Nigeria.

Methods

The data for the study were derived from the 2018 Nigeria Demographic and Health Survey and comprised a weighted sample of 127,545 birth histories of childbearing women. Descriptive and analytical analyses were carried out, including frequency tables and multivariate using Cox proportional regression. The results were presented as hazard ratios (HR) with 95% confidence intervals (CIs). Data were analyzed using Stata software version 15.1.

Results

The results showed that 14.3% of the sampled birth histories of the childbearing women were children who died before age 5. The results further showed that 97.7% of the children were of mothers who have health insurance and over one-half (56.5%) were children whose mothers had adequate healthcare services utilisation. The risk of under-five death was significantly lower among the children of mothers who were covered by health insurance (HR: 0.66, CI: 0.42–1.02) and those whose mothers utilised adequate healthcare services (HR: 0.78, CI: 0.68–0.90). A similar result was observed among children whose mothers reported that distance to the health facility was not a problem (HR: 0.81, CI: 0.72–0.86). Some mothers’ characteristics including educational attainment, wealth quintile and region of residence significantly influenced the risk of U-5 M.

Conclusions

The study established that maternal health insurance coverage and adequate healthcare services utilisation were found to be protective factors against the risk of U-5 M. Also, the revealed low health insurance coverage of mothers calls for more pragmatic policy and intervention programmes through health insurance to achieve SDGs targets of ending preventable deaths of children under 5 years of age and ensuring quality, as well as universal access to maternal and child healthcare services.
Reading comprehension test fairness across gender and mode of learning: insights from IRT-based differential item functioning analysis
Authors: Moradi Elahe , Ghabanchi Zargham , Pishghadam Reza
Published: September 2022

Given the significance of the test fairness, this study aimed to investigate a reading comprehension test for evidence of differential item functioning (DIF) based on English as a Foreign Language (EFL) learners’ gender and their mode of learning (conventional vs. distance learning). To this end, 514 EFL learners were asked to take a 30-item multiple-choice reading comprehension test. After establishing the unidimensionality and local independence of the data as prerequisites to DIF analyses, Rasch model-based DIF analysis was conducted across learners’ gender and their mode of learning. The results showed that there were two gender-DIF items which functioned differentially in favor of female respondents. Also, DIF analysis in terms of EFL learners’ mode of learning revealed that there were no DIF items across the two target groups indicating that the reading comprehension test functioned the same way for learners who enjoyed conventional learning compared to those who experienced distance and self-directed learning. In the end, the findings were discussed and implications were provided.
Azimuthal differences and changes in strain rate and stress of the Japanese Islands deduced from geophysical data
Authors: Kosugi Issei , Mitsui Yuta
Published: September 2022

Geodetic and seismological observations have shown discrepancies between azimuths of maximum contraction (strain rate) and maximum compression (stress). These discrepancies can be the results of the superposition of localized or transient mechanical processes such as fault coupling during seismic cycles. Rich sets of recent geophysical data allow us to conduct spatiotemporal imaging of the discrepancies. Here, we estimate the spatiotemporal evolution in the strain-rate fields of the Japanese Islands with optimized smoothing distances from 1997 to 2021 using Global Navigation Satellite System (GNSS) data, and investigate how the maximum contraction axes of horizontal strain rates differ from those of horizontal stress based on earthquake focal mechanisms. Several characteristic results are observed for each region within the Japanese Islands. Both azimuths of the strain rates and stress differ by more than 60° over hundreds of kilometers from the Kanto region to along the Nankai Trough, related to seismotectonics due to the dual subduction of the Philippine Sea plate and the Pacific plate beneath the Japanese Islands. The differences in the azimuths imply the effect of the very long-term stable subduction of the Pacific plate. We find that the azimuthal differences tend to be small along tectonic zones with active inland earthquakes and high strain rates on the back-arc sides. We also find that the 2011 off the Pacific coast of Tohoku earthquake caused notable azimuthal differences in the strain rates and the stress in the Tohoku region. The strength of fault may cause lower response sensitivity of seismological stress to major earthquakes than geodetic strain rate. Our dataset has wide spatiotemporal coverage and can serve as a basis for further research, for example, to estimate the current fault conditions during seismic cycles.

Graphical Abstract