bluuebunny/crossref_metadata_2025 huggingface dataset:
Human amniotic epithelial cell-derived extracellular vesicles provide an extracellular matrix-based microenvironment for corneal injury repair
Authors: Hu Shuqin , Wang Zhe , Jin Caixia , Chen Qizhen , Fang Yuchen , Jin Jiahui , Chen Jie , Lu Lixia , Tian Haibin , Xu Jingying , Gao Furong , Wang Juan , Zhang Jieping , Cui Hong-Ping , Xu Guo-Tong , Ou Qingjian
Published: September 2022

To study the biological functions and applications of human amniotic epithelial cell-derived extracellular vesicles (hAEC-EVs), the cargos of hAEC-EVs were analyzed using miRNA sequencing and proteomics analysis. The hAECs and hAEC-EVs in this study had specific characteristics. Multi-omics analyses showed that extracellular matrix (ECM) reorganization, inhibition of excessive myofibroblasts, and promotion of target cell adhesion to the ECM were their primary functions. We evaluated the application of hAEC-EVs for corneal alkali burn healing in rabbits and elucidated the fundamental mechanisms. Slit-lamp images revealed that corneal alkali burns induced central epithelial loss, stromal haze, iris, and pupil obscurity in rabbits. Slit-lamp examination and histological findings indicated that hAEC-EVs facilitated re-epithelialization of the cornea after alkali burns, reduced scar formation and promoted the restoration of corneal tissue transparency. Significantly fewer α-SMA-positive myofibroblasts were observed in the hAEC-EV-treated group than the PBS group. HAEC-EVs effectively promoted the proliferation and migration of hCECs and hCSCs in vitro and activated the focal adhesion signaling pathway. We demonstrated that hAEC-EVs were excellent cell-free candidates for the treatment of ECM lesion-based diseases, including corneal alkali burns. HAEC-EVs promoted ECM reorganization and cell adhesion of target tissues or cells via orderly activation of the focal adhesion signaling pathway.
Prevalence of pulmonary tuberculosis and associated factors among adults living with HIV/AIDS attending public hospitals in Shashamene Town, Oromia Region, South Ethiopia
Authors: Gisso Belayneh Tadesse , Hordofa Mesfin Worku , Ormago Moges Desta
Published: September 2022

Objective:

This study was aimed to assess the prevalence of pulmonary tuberculosis and its associated factors among adults living with HIV/AIDS attending Public Hospitals, Shashamene Town, Oromia Region, South Ethiopia.

Methods:

A cross-sectional study was conducted from November 2020 to February 2021 among Adults Living with HIV/AIDS attending Public Hospitals in Shashamene Town, Oromia Region, South Ethiopia. A sputum sample was collected and analyzed using Xpert MTB/RIF assay and blood sample was collected to count CD4 using BD FACSPresto analyzer. Semi-structured questionnaires were used to collect data. SPSS version 25 software was used for statistical analysis and a p value of <0.05 was considered as statistically significant.

Results:

In this study, the overall prevalence of pulmonary tuberculosis among adults living with HIV/AIDS attending the Public Hospitals was 23.5% (5% confidence interval: 18.26, 29.13). Variables such as age range of 50–64 years, female gender, occupation with house wife, and World Health Organization stage (III and IV) were significantly associated with prevalence of tuberculosis infection.

Conclusion:

The prevalence of tuberculosis in our study site was high. There is a need for regular screening of people living with HIV/AIDS for TB using highly sensitive method like Xpert MTB/RIF assay to know their TB status as well as early commencement of anti-TB.
Thinking outside Earth’s box—how might heredity and evolution differ on other worlds?
Authors: Noor Mohamed A. F.
Published: September 2022

Scholars and the public conceive of extraterrestrial life through the lens of "life as we know it" on Earth. However, assumptions based on centuries of study around heredity and evolution on Earth may not apply to life truly independent forms of life, and some perspectives accepted or ruled out in the nineteenth century may need to be re-evaluated for life outside of Earth. In honor of the 200th birthday of Mendel, and to provide raw material for the creativity of storytellers, filmmakers, and the public, this thought experiment essay revisits a handful of classic concepts and approaches, as well as some unusual forms of life on Earth, to posit whether different types of genetics and evolution may exist in truly independent extraterrestrial forms. While fundamental evolutionary processes like natural selection and genetic drift are likely to still apply at least similarly in independent life forms, inheritance may be quite radically different from that envisioned by Mendel and others since.
OsFTL4, an FT-like Gene, Regulates Flowering Time and Drought Tolerance in Rice (Oryza sativa L.)
Authors: Gu Houwen , Zhang Kunming , Chen Jie , Gull Sadia , Chen Chuyan , Hou Yafei , Li Xiangbo , Miao Jun , Zhou Yong , Liang Guohua
Published: September 2022

The initiation of flowering in cereals is a critical process influenced by environmental and endogenous signals. Flowering Locus T-like (FT-like) genes encode the main signals for flowering. Of the 13 FT-like genes in the rice genome, Hd3a/OsFTL2 and RFT1/OsFTL3 have been extensively studied and revealed to be critical for flowering. In this study, a rice FT-like gene, OsFTL4, was functionally characterized. Specifically, osftl4 mutants were generated using a CRISPR/Cas9 system. Compared with the wild-type control (Guangluai 4), the osftl4-1 and osftl4-2 mutants flowered 9.6 and 5.8 days earlier under natural long-day and short-day conditions, respectively. Additionally, OsFTL4 was mainly expressed in the vascular tissue, with the resulting OsFTL4 protein localized in both the nucleus and cytoplasm. Furthermore, OsFTL4 was observed to compete with Hd3a for the interaction with multiple 14-3-3 proteins. An analysis of the effects of simulated drought stress suggested that silencing OsFTL4 enhances drought tolerance by decreasing stomatal conductance and water loss. These results indicate that OsFTL4 helps integrate the flowering process and the drought response in rice.
The proportion and phenotypic changes of CD4+CD25−Foxp3+ T cells in patients with untreated rheumatoid arthritis
Authors: Ju Bomiao , Zhu Li , Wang Jing , Zheng Jian , Hao Zhiming , Luo Jing , Zhang Jing , Hu Nan , An Qi , Feng Xiuyuan , Huo Yongwei , He Lan
Published: September 2022

Objective

CD4+CD25+Foxp3+ regulatory T (Treg) cell-mediated immunosuppression is an essential mechanism of rheumatoid arthritis (RA). However, little is known regarding the specific role of CD4+CD25−Foxp3+ Treg cells in RA. This study aimed to investigate the frequency of circulating CD4+CD25−Foxp3+ Treg cells and their role in RA.

Methods

Sixty-one untreated RA patients and 40 healthy controls (HCs) were enrolled in this study. The proportion of CD4+CD25−Foxp3+ T cells and CD4+CD25+Foxp3+ Tregs; the levels of CTLA4, GITR, Helios, and ICOS; and the production of IL-17A, IFN-γ, and IL-10 were assessed by flow cytometry. The correlation of CD4+CD25–Foxp3+ T cells and CD4+CD25+Foxp3+ Tregs with the clinical indicators was conducted by Spearman correlation analysis.

Results

The proportion of CD4+CD25–Foxp3+ T cells was elevated in RA and positively correlated with disease activity. CD4+CD25–Foxp3+ T cells expressed less Helios and produced more IFN-γ than conventional Tregs in RA. Additionally, the proportion of CD4+CD25–Foxp3+ T cells was positively correlated with DAS28 score, IgG titer, and anti-CCP titer.

Conclusions

These data indicate that CD4+CD25−Foxp3+ T cells in RA exhibit several different functional properties from conventional Tregs and are correlated with RA disease activity.
Comparative study of a modified double-lumen tube ventilation control connector and traditional connector in clinical use: a randomised-controlled trial
Authors: Liu Chang , Zhao Yuanyu , Li You , Guan Huiwen , Feng Junjie , Cheng Shengquan , Wang Xin , Wang Yue , Sun Xufang
Published: September 2022

Background

A Y-shaped rotatable connector (YRC) for double-lumen tubes (DLT) is invented and compared with the traditional connector (Y-shaped connector, YC).

Methods

Sixty patients with ASA grade I-III, aged ≥ 18 years, who needed to insert a DLT for thoracic surgery were recruited and assigned into the YRC group (n = 30) and the YC group (n = 30) randomly. The primary endpoints included the inhaled air concentration (Fi) and the exhaled air concentration (Et) of sevoflurane before and after the switch between two-lung ventilation and one-lung ventilation at different times, positioning time, and switching time. The secondary endpoints were the internal gas volume of the two connectors, airway pressure, and the sputum suction time.

Results

The Et and Fi of the YRC group and the YC group were significantly different (all p < 0.05) at 5s, 10s, and 30s after the patient switched from two-lung ventilation to one-lung ventilation. The positioning time of the YRC group was less than YC group (89.75 ± 14.28 s vs 107.80 ± 14.96 s, p < 0.05), as well as the switching time (3.60 ± 1.20 s vs 9.05 ± 2.53 s, p < 0.05) and the internal gas volume (17.20 ml vs 24.12 ml). There was no difference in airway pressure and the sputum suction time in two groups.

Conclusion

Compared with YC, YRC was beneficial for maintaining depth of anesthesia, improves efficiency for the switch between one-lung and two-lung ventilation, and shortens the tube positioning time.
Family functioning and health-related quality of life of inpatients with coronary heart disease: a cross-sectional study in Lanzhou city, China
Authors: Zhang Hongchen , Wang Yanhong , Cai Xiaoqing , Tang Nan , Wei Siqi , Yang Yanwei
Published: September 2022

Background

A key outcome in coronary heart disease (CHD) is Health Related Quality of Life (HRQoL), and family functioning is important in the management of CHD. But few studies have examined both together, and little is known about them among inpatients with CHD in less developed areas of China. Therefore, this study aimed to assess the HRQoL and family functioning status of inpatients with CHD in Lanzhou from Northwest China, and identify the factors that affect their HRQoL.

Methods

A cross‑sectional study was conducted in 224 CHD inpatients at one major hospital. Sociodemographic data and disease information of CHD inpatients were collected by face-to-face using a structured questionnaire and data were also obtained from patient medical records. HRQoL was measured using the Sickness Impact Profile (SIP). Family functioning was measured using the family APGAR index. Multiple binary logistic regression analysis (MBLRA) was used to explore potential risk factors associated with HRQoL, and Pearson’s correlations were used to assess the relationship between family functioning and HRQoL.

Results

The overall, physical and psychosocial SIP scores were 25.03 ± 8.52, 18.61 ± 9.90 and 28.08 ± 9.64, respectively. The total family APGAR score was 6.11 ± 2.45. MBLRA found older age, poorer cardiac function and more severe disease were associated with poorer HRQoL, while better family functioning, higher monthly income, and urban living were associated with better HRQoL. Family functioning was weakly to moderately correlated with total and psychosocial HRQoL.

Conclusions

Older and less affluent inpatients with lower educational level, less family support and more severe CHD have poorest quality of life, and health care providers should consider interventions to support them.
Impact of metal artifact reduction algorithm on gross tumor volume delineation in tonsillar cancer: reducing the interobserver variation
Authors: Fukugawa Yoshiyuki , Toya Ryo , Matsuyama Tomohiko , Watakabe Takahiro , Shimohigashi Yoshinobu , Kai Yudai , Matsumoto Tadashi , Oya Natsuo
Published: September 2022

Background

Patients with tonsillar cancer (TC) often have dental fillings that can significantly degrade the quality of computed tomography (CT) simulator images due to metal artifacts. We evaluated whether the use of the metal artifact reduction (MAR) algorithm reduced the interobserver variation in delineating gross tumor volume (GTV) of TC.

Methods

Eighteen patients with TC with dental fillings were enrolled in this study. Contrast-enhanced CT simulator images were reconstructed using the conventional (CTCONV) and MAR algorithm (CTMAR). Four board-certified radiation oncologists delineated the GTV of primary tumors using routine clinical data first on CTCONV image datasets (GTVCONV), followed by CTCONV and CTMAR fused image datasets (GTVMAR) at least 2 weeks apart. Intermodality differences in GTV values and Dice similarity coefficient (DSC) were compared using Wilcoxon’s signed-rank test.

Results

GTVMAR was significantly smaller than GTVCONV for three observers. The other observer showed no significant difference between GTVCONV and GTVMAR values. For all four observers, the mean GTVCONV and GTVMAR values were 14.0 (standard deviation [SD]: 7.4) cm3 and 12.1 (SD: 6.4) cm3, respectively, with the latter significantly lower than the former (p < 0.001). The mean DSC of GTVCONV and GTVMAR was 0.74 (SD: 0.10) and 0.77 (SD: 0.10), respectively, with the latter significantly higher than that of the former (p < 0.001).

Conclusions

The use of the MAR algorithm led to the delineation of smaller GTVs and reduced interobserver variations in delineating GTV of the primary tumors in patients with TC.
Experience and confidence in health technologies: evidence from malaria testing and treatment in Western Kenya
Authors: Mangeni Judith N. , Abel Lucy , Taylor Steve M. , Obala Andrew , O’Meara Wendy Prudhomme , Saran Indrani
Published: September 2022

Background

Low adoption of effective health technologies increases illness morbidity and mortality worldwide. In the case of malaria, effective tools such as malaria rapid diagnostic tests (RDTs) and artemisinin-combination therapies (ACTs) are both under-used and used inappropriately. Individuals’ confidence in RDTs and ACTs likely affects the uptake of these tools.

Methods

In a cohort of 36 households (280 individuals) in Western Kenya observed for 30 months starting in June 2017, we examined if experience with RDTs and ACTs changes people’s beliefs about these technologies and how those beliefs affect treatment behavior. Household members requested a free RDT from the study team any time they suspected a malaria illness, and positive RDT results were treated with a free ACT. We conducted annual, monthly, and sick visit surveys to elicit beliefs about the accuracy of malaria RDT results and the effectiveness of ACTs. Beliefs were elicited on a 5-point Likert scale from “very unlikely” to “very likely.”

Results

Over the study period, the percentage of survey respondents that said a hypothetical negative RDT result was “very likely” to be correct increased from approximately 55% to 75%. Controlling for initial beliefs, people who had been tested at least once with an RDT in the past year had 3.6 times higher odds (95% CI [1 1.718 7.679], P = 0.001) of saying a negative RDT was “very likely” to be correct. Confidence in testing was associated with treatment behavior: those who believed a negative RDT was “very likely” to be correct had 1.78 times higher odds (95% CI [1.079 2.934], P = 0.024) of adhering to a negative RDT result (by not taking ACTs) than those who were less certain about the accuracy of negative RDTs. Adherence to a negative test also affected subsequent beliefs: controlling for prior beliefs, those who had adhered to their previous test result had approximately twice the odds (OR = 2.19, 95% CI [1.661 2.904], P < 0.001) of saying that a hypothetical negative RDT was “very likely” to be correct compared to those who had not adhered.

Conclusions

Our results suggest that greater experience with RDTs can not only increase people’s confidence in their accuracy but also improve adherence to the test result.
BertSRC: transformer-based semantic relation classification
Authors: Lee Yeawon , Son Jinseok , Song Min
Published: September 2022

The relationship between biomedical entities is complex, and many of them have not yet been identified. For many biomedical research areas including drug discovery, it is of paramount importance to identify the relationships that have already been established through a comprehensive literature survey. However, manually searching through literature is difficult as the amount of biomedical publications continues to increase. Therefore, the relation classification task, which automatically mines meaningful relations from the literature, is spotlighted in the field of biomedical text mining. By applying relation classification techniques to the accumulated biomedical literature, existing semantic relations between biomedical entities that can help to infer previously unknown relationships are efficiently grasped. To develop semantic relation classification models, which is a type of supervised machine learning, it is essential to construct a training dataset that is manually annotated by biomedical experts with semantic relations among biomedical entities. Any advanced model must be trained on a dataset with reliable quality and meaningful scale to be deployed in the real world and can assist biologists in their research. In addition, as the number of such public datasets increases, the performance of machine learning algorithms can be accurately revealed and compared by using those datasets as a benchmark for model development and improvement. In this paper, we aim to build such a dataset. Along with that, to validate the usability of the dataset as training data for relation classification models and to improve the performance of the relation extraction task, we built a relation classification model based on Bidirectional Encoder Representations from Transformers (BERT) trained on our dataset, applying our newly proposed fine-tuning methodology. In experiments comparing performance among several models based on different deep learning algorithms, our model with the proposed fine-tuning methodology showed the best performance. The experimental results show that the constructed training dataset is an important information resource for the development and evaluation of semantic relation extraction models. Furthermore, relation extraction performance can be improved by integrating our proposed fine-tuning methodology. Therefore, this can lead to the promotion of future text mining research in the biomedical field.
Identification and functional characterization of BICD2 as a candidate disease gene in an consanguineous family with dilated cardiomyopathy
Authors: Luo Kai , Zheng Chenqing , Luo Rong , Cao Xin , Sun Huajun , Ma Huihui , Huang Jichang , Yang Xu , Wu Xiushan , Li Xiaoping
Published: September 2022

Background

Familial dilated cardiomyopathy (DCM) is a genetic cardiomyopathy that is associated with reduced left ventricle function or systolic function. Fifty-one DCM-causative genes have been reported, most of which are inherited in an autosomal dominant manner. However, recessive DCM-causative gene is rarely observed.

Methods

Whole-exome sequencing (WES) was performed in a consanguineous family with DCM to identify candidate variants. Sanger sequencing was utilized to confirm the variant. We then checked the DCM candidate gene in 210 sporadic DCM cases. We next explored BICD2 function in both embryonic and adult bicd2-knockout zebrafish models. In vivo cardiac function of bicd2-knockout fish was detected by echocardiography and RNA-seq.

Results

We identified an autosomal recessive and evolutionarily conserved missense variant, NM_001003800.1:c.2429G > A, in BICD2, which segregated with the disease phenotype in a consanguineous family with DCM. Furthermore, we confirmed the presence of BICD2 variants in 3 sporadic cases. Knockout of bicd2 resulted in partial embryonic lethality in homozygotes, suggesting a vital role for bicd2 in embryogenesis. Heart dilation and decreased ejection fraction, cardiac output and stroke volume were observed in bicd2-knockout zebrafish, suggesting a phenotype similar to human DCM. Furthermore, RNA-seq confirmed a larger transcriptome shift in in bicd2 homozygotes than in heterozygotes. Gene set enrichment analysis of bicd2-deficient fish showed the enrichment of altered gene expression in cardiac pathways and mitochondrial energy metabolism.

Conclusions

Our study first shows that BICD2 is a novel candidate gene associated with familial DCM, and our findings will facilitate further insights into the molecular pathological mechanisms of DCM.
Beyond the vaccines: a glance at the small molecule and peptide-based anti-COVID19 arsenal
Authors: Nepali Kunal , Sharma Ram , Sharma Sachin , Thakur Amandeep , Liou Jing-Ping
Published: September 2022

Unprecedented efforts of the researchers have been witnessed in the recent past towards the development of vaccine platforms for the control of the COVID-19 pandemic. Albeit, vaccination stands as a practical strategy to prevent SARS-CoV-2 infection, supplementing the anti-COVID19 arsenal with therapeutic options such as small molecules/peptides and antibodies is being conceived as a prudent strategy to tackle the emerging SARS-CoV-2 variants. Noteworthy to mention that collective efforts from numerous teams have led to the generation of a voluminous library composed of chemically and mechanistically diverse small molecules as anti-COVID19 scaffolds. This review article presents an overview of medicinal chemistry campaigns and drug repurposing programs that culminated in the identification of a plethora of small molecule-based anti-COVID19 drugs mediating their antiviral effects through inhibition of proteases, S protein, RdRp, ACE2, TMPRSS2, cathepsin and other targets. In light of the evidence ascertaining the potential of small molecule drugs to approach conserved proteins required for the viral replication of all coronaviruses, accelerated FDA approvals are anticipated for small molecules for the treatment of COVID19 shortly. Though the recent attempts invested in this direction in pursuit of enrichment of the anti-COVID-19 armoury (chemical tools) are praiseworthy, some strategies need to be implemented to extract conclusive benefits of the recently reported small molecule viz. (i) detailed preclinical investigation of the generated anti-COVID19 scaffolds (ii) in-vitro profiling of the inhibitors against the emerging SARS-CoV-2 variants (iii) development of assays enabling rapid screening of the libraries of anti-COVID19 scaffold (iv) leveraging the applications of machine learning based predictive models to expedite the anti-COVID19 drug discovery campaign (v) design of antibody–drug conjugates.
Higher pulse wave velocity in young adult offspring of mothers with type 1 diabetes: a case–control study
Authors: Korpijaakko Cedric A. , Eriksson Mia D. , Wasenius Niko S. , Klemetti Miira M. , Teramo Kari , Kautiainen Hannu , Eriksson Johan G. , Laine Merja K.
Published: September 2022

Background

Offspring of mothers with type 1 diabetes have an increased risk for acquiring early onset cardiovascular disease (CVD). Arterial stiffness, measured as pulse wave velocity (PWV), is a non-invasive biomarker for CVD risk assessment. Our aim is to determine whether PWV is increased in young adult offspring of mothers with type 1 diabetes.

Methods

This is a case–control study carried out in the hospital district of Helsinki and Uusimaa, Finland. 75 offspring of mothers with type 1 diabetes (cases) and 84 offspring of mothers without diabetes (controls), aged 18–23 years, were enrolled in this study. All participants attended clinical assessments, including questionnaires and laboratory tests. Carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and PWV ratio were measured from each participant using the Complior Analyse mechanotransducer (Alam Medical, France). Student’s t-test and chi-squared test were used to assess differences between the groups. Stata 17.0, StataCorp LP (College Station, TX, USA) statistical package was used for the analysis.

Results

We did not observe any differences in conventional CVD risk factors: systolic blood pressure, LDL, HbA1c, and smoking between cases and controls. We detected higher cfPWV in cases 6.5 (SD ± 1.2) m/s than in controls 6.2 (SD ± 0.7) m/s, p = 0.049, after adjustments for BMI, smoking, mean arterial pressure, height, and pulse rate was made. We did not observe any difference between cases and controls regarding crPWV or PWV ratio. Additionally, we detected no sex differences.

Conclusions

We report a novel finding of signs of increased arterial stiffness already in young adult offspring of mothers with type 1 diabetes compared to matched offspring of mothers without diabetes. Our finding suggests that exposure to an adverse intrauterine environment of type 1 diabetes mothers may affect the vascular health of offspring already in young adulthood. Additional research within this topic is warranted.
TRIM36 inhibits tumorigenesis through the Wnt/β-catenin pathway and promotes caspase-dependent apoptosis in hepatocellular carcinoma
Authors: Tong Qing , Yi Mingyu , Kong Panpan , Xu Lin , Huang Wukui , Niu Yue , Gan Xiaojing , Zhan Huan , Tian Rui , Yan Dong
Published: September 2022

Background

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has an extremely poor prognosis. We aimed to determine the latent relationships between TRIM36 regulation of apoptosis and the Wnt/β-catenin pathway in HCC.

Methods

Immunohistochemistry and western blotting were used to characterize the aberrant expression of TRIM36 in HCC and adjacent tissues. Clinical information was analyzed using Kaplan–Meier and Cox methods. RNA-seq of potential targets was conducted to detect the regulation of TRIM36. Apoptosis assays and cellular proliferation, invasion and migration were conducted in a loss- and gain-of-function manner in cultured cells to determine the biological functions of TRIM36. A rescue experiment was conducted to confirm the role of Wnt/β-catenin signaling in TRIM36 regulation. Finally, in vivo experiments were conducted using cell line-derived xenografts in nude mice to validate the central role of TRIM36 in HCC.

Results

TRIM36 expression was significantly downregulated in HCC tissues compared to adjacent non-tumor tissues. TRIM36 repressed the proliferation, migration, and invasion of Huh7 and HCCLM3 cells, whereas it stimulated apoptosis. Wnt/β-catenin signaling was inhibited by TRIM36, and rescue experiments highlighted its importance in HCC proliferation, migration, and invasion. In vivo experiments further confirmed the effects of sh-TRIM36 on HCC tumorigenesis, inhibition of apoptosis, and promotion of Wnt/β-catenin signaling.

Conclusion

Our study is the first to indicate that TRIM36 acts as a tumor suppressor in HCC. TRIM36 activates apoptosis and inhibits cellular proliferation, invasion, and migration via the Wnt/β-catenin pathway, which may serve as an important biomarker and promising therapeutic target for HCC.
Anopheline diversity in urban and peri-urban malaria foci: comparison between alternative traps and seasonal effects in a city in the Western Brazilian Amazon
Authors: Meireles Anne Caroline Alves , da Silva Lucas Rosendo , Simplício Marlon Ferreira , de Lima Alzemar Alves , Rios Flávia Geovana Fontineles , de Menezes Carla Augusta , Feitoza Luiz Henrique Maciel , Julião Genimar Rebouças
Published: September 2022

Background

Continuous vector surveillance and sustainable interventions are mandatory in order to prevent anopheline proliferation (or spread to new areas) and interrupt malaria transmission. Anopheline abundance and richness were evaluated in urban and peri-urban malaria foci at a medium-sized city in the Brazilian Amazon, comparing the protected human landing catch technique (PHLC) and alternative sampling methods over different seasonal periods. Additional information was assessed for female feeding behaviour and faunal composition.

Methods

Anophelines were sampled bimonthly in four urban and peri-urban sites in the city of Porto Velho, state of Rondônia, Brazil. The average number of captured mosquitoes was compared between an PHLC (gold standard), a tent trap (Gazetrap), and a barrier screen by means of generalized linear mixed models (GLMM), which also included season and environment (peri-urban/urban) as predictors.

Results

Overall, 2962 Anopheles individuals belonging to 12 species and one complex were caught; Anopheles darlingi represented 86% of the individuals. More mosquitoes were captured in the peri-urban setting, and the urban setting was more diverse. The model estimates that significantly more anophelines were collected by PHLC than by the Screen method, and Gazetrap captured fewer individuals. However, the Screen technique yielded more blood-engorged females. The peak hours of biting activity were from 6 to 7 p.m. in urban areas and from 7 to 8 p.m. in peri-urban areas.

Conclusions

Although peri-urban settings presented a greater abundance of anophelines, Shannon and Simpson diversities were higher in urban sites. Each technique proved to be useful, depending on the purpose: PHLC was more effective in capturing the highest anopheline densities, Gazetrap caught the greatest number of species, and the barrier screen technique captured more engorged individuals. There was no seasonal effect on Anopheles assemblage structure; however, a more diverse fauna was caught in the transitional season. Biting activity was more intense from 6 to 8 p.m., with a predominance of An. darlingi.
Activation of NMDA receptors in brain endothelial cells increases transcellular permeability
Authors: Kim Kyu-Sung , Jeon Min Tae , Kim Eun Seon , Lee Chan Hee , Kim Do-Geun
Published: September 2022

Neurovascular coupling is a precise mechanism that induces increased blood flow to activated brain regions, thereby providing oxygen and glucose. In this study, we hypothesized that N-methyl-D-aspartate (NMDA) receptor signaling, the most well characterized neurotransmitter signaling system which regulates delivery of essential molecules through the blood–brain barrier (BBB). Upon application of NMDA in both in vitro and in vivo models, increased delivery of bioactive molecules that was mediated through modulation of molecules involved in molecular delivery, including clathrin and caveolin were observed. Also, NMDA activation induced structural changes in the BBB and increased transcellular permeability that showed regional heterogeneity in its responses. Moreover, NMDA receptor activation increased endosomal trafficking and facilitated inactivation of lysosomal pathways and consequently increased molecular delivery mediated by activation of calmodulin-dependent protein kinase II (CaMKII) and RhoA/protein kinase C (PKC). Subsequent in vivo experiments using mice specifically lacking NMDA receptor subunit 1 in endothelial cells showed decreased neuronal density in the brain cortex, suggesting that a deficiency in NMDA receptor signaling in brain endothelial cells induces neuronal losses. Together, these results highlight the importance of NMDA-receptor-mediated signaling in the regulation of BBB permeability that surprisingly also affected CD31 staining.
In vivo measurement of intradiscal pressure changes related to thrust and non-thrust spinal manipulation in an animal model: a pilot study
Authors: Reed William R. , Liebschner Michael A. K. , Lima Carla R. , Singh Harshvardhan , Hurt Christopher P. , Martins Daniel F. , Cox James M. , Gudavalli Maruti R.
Published: September 2022

Background

The intervertebral disc is a known back pain generator and is frequently the focus of spinal manipulative therapy evaluation and treatment. The majority of our current knowledge regarding intradiscal pressure (IDP) changes related to spinal manual therapy involves cadaveric studies with their inherent limitations. Additional in vivo animal models are needed to investigate intervertebral disc physiological and molecular mechanisms related to spinal manipulation and spinal mobilization treatment for low back disorders.

Methods

Miniature pressure catheters (Millar SPR-1000) were inserted into either the L4-L5 or L5-L6 intervertebral disc of 3 deeply anesthetized adult cats (Oct 2012-May 2013). Changes in IDP were recorded during delivery of instrument-assisted spinal manipulation (Activator V® and Pulstar®) and motorized spinal flexion with/without manual spinous process contact.

Results

Motorized flexion of 30° without spinous contact decreased IDP of the L4-L5 disc by ~ 2.9 kPa, while physical contact of the L4 spinous process decreased IDP an additional ~ 1.4 kPa. Motorized flexion of 25° with L5 physical contact in a separate animal decreased IDP of the L5-L6 disc by ~ 1.0 kPa. Pulstar® impulses (setting 1–3) increased IDP of L4-L5 and L5-L6 intervertebral discs by ~ 2.5 to 3.0 kPa. Activator V® (setting 1–4) impulses increased L4-L5 IDP to a similar degree. Net changes in IDP amplitudes remained fairly consistent across settings on both devices regardless of device setting suggesting that viscoelastic properties of in vivo spinal tissues greatly dampen superficially applied manipulative forces prior to reaching deep back structures such as the intervertebral disc.

Conclusions

This study marks the first time that feline in vivo changes in IDP have been reported using clinically available instrument-assisted spinal manipulation devices and/or spinal mobilization procedures. The results of this pilot study indicate that a feline model can be used to investigate IDP changes related to spinal manual therapy mechanisms as well as the diminution of these spinal manipulative forces due to viscoelastic properties of the surrounding spinal tissues. Additional investigation of IDP changes is warranted in this and/or other in vivo animal models to provide better insights into the physiological effects and mechanisms of spinal manual therapy at the intervertebral disc level.
Systemic injection of nicotinic acetylcholine receptor antagonist mecamylamine affects licking, eyelid size, and locomotor and autonomic activities but not temporal prediction in male mice
Authors: Kaneko Shohei , Niki Yasuyuki , Yamada Kota , Nasukawa Daiki , Ujihara Yusuke , Toda Koji
Published: September 2022

Nicotinic acetylcholine receptors are thought to be associated with a wide range of phenomena, such as movement, learning, memory, attention, and addiction. However, the causal relationship between nicotinic receptor activity and behavior remains unclear. Contrary to the studies that examined the functions of muscarinic acetylcholine receptors, the role of the nicotinic acetylcholine receptors on behavior has not been examined as extensively. Here, we examined the effects of intraperitoneal injection of mecamylamine, a nicotinic acetylcholine receptor antagonist, on the performance of male mice in a head-fixed temporal conditioning task and a free-moving open-field task. The head-fixed experimental setup allowed us to record and precisely quantify the licking response while the mice performed the behavioral task with no external cues. In addition, by combining the utility of the head-fixed experimental design with computer vision analysis based on deep learning algorithms, we succeeded in quantifying the eyelid size of awake mice. In the temporal conditioning task, we delivered a 10% sucrose solution every 10 s using a blunt-tipped needle placed within the licking distance of the mice. After the training, the mice showed increased anticipatory licking toward the timing of sucrose delivery, suggesting that the mice could predict the timing of the reward. Systemic injection of mecamylamine decreased licking behavior and caused eye closure but had no effect on learned conditioned predictive behavior in the head-fixed temporal conditioning task. In addition, the injection of mecamylamine decreased spontaneous locomotor activity in a dose-dependent manner in the free-moving open-field task. The results in the open-field experiments further revealed that the effect of mecamylamine on fecal output and urination, suggesting the effects on autonomic activities. Our achievement of successful eyelid size recording has potential as a useful approach in initial screening for drug discovery. Our study paves a way forward to understanding the role of nicotinic acetylcholine receptors on learning and behavior.
Hypoxia-induced exosomal circPDK1 promotes pancreatic cancer glycolysis via c-myc activation by modulating miR-628-3p/BPTF axis and degrading BIN1
Authors: Lin Jiewei , Wang Xinjing , Zhai Shuyu , Shi Minmin , Peng Chenghong , Deng Xiaxing , Fu Da , Wang Jiancheng , Shen Baiyong
Published: September 2022

Background

circRNA has been established to play a pivotal role in tumorigenesis development in a variety of cancers; nevertheless, the biological functions and molecular mechanisms of hypoxia-induced exosomal circRNAs in pancreatic cancer remain largely unknown.

Methods

Differentially expressed circRNAs in exosomes between hypoxic exosomes and normoxic exosomes in PC cells were verified by RNA sequencing. The expression of circPDK1 in PC tumors and PC patients was evaluated by qRT-PCR and ISH, and the biological functions of circPDK1 in PC were verified through a series of in vitro and in vivo experiments. Using Western blotting, Co-IP, RNA pull-down, ChIP, RIP, dual-luciferase assays, and rescue experiments, the underlying mechanism of circPDK1 was verified.

Results

CircPDK1 was highly abundant in PC tumor tissues and serum exosomes and was associated with poor survival. Exosomal circPDK1 significantly promoted PC cell proliferation, migration, and glycolysis both in vitro and in vivo. Mechanistically, circPDK1 could be activated by HIF1A at the transcriptional level and sponges miR-628-3p to activate the BPTF/c-myc axis. In addition, circPDK1 serves as a scaffold that enhances the interaction between UBE2O and BIN1, inducing the UBE2O-mediated degradation of BIN1.

Conclusions

We found that circPDK1 was activated by HIF1A at the transcriptional level by modulating the miR-628-3p/BPTF axis and degrading BIN1. Exosomal circPDK1 is a promising biomarker for PC diagnosis and prognosis and represents a potential therapeutic target for PC.
Administration of vitamin D and its metabolites in critically ill adult patients: an updated systematic review with meta-analysis of randomized controlled trials
Authors: Menger Johannes , Lee Zheng-Yii , Notz Quirin , Wallqvist Julia , Hasan M. Shahnaz , Elke Gunnar , Dworschak Martin , Meybohm Patrick , Heyland Daren K. , Stoppe Christian
Published: September 2022

Background

The clinical significance of vitamin D administration in critically ill patients remains inconclusive. The purpose of this systematic review with meta-analysis was to investigate the effect of vitamin D and its metabolites on major clinical outcomes in critically ill patients, including a subgroup analysis based on vitamin D status and route of vitamin D administration.

Methods

Major databases were searched through February 9, 2022. Randomized controlled trials of adult critically ill patients with an intervention group receiving vitamin D or its metabolites were included. Random-effect meta-analyses were performed to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Risk of bias assessment included the Cochrane tool for assessing risk of bias in randomized trials.

Results

Sixteen randomized clinical trials with 2449 patients were included. Vitamin D administration was associated with lower overall mortality (16 studies: risk ratio 0.78, 95% confidence interval 0.62–0.97, p = 0.03; I2 = 30%), reduced intensive care unit length of stay (12 studies: mean difference − 3.13 days, 95% CI − 5.36 to − 0.89, n = 1250, p = 0.006; I2 = 70%), and shorter duration of mechanical ventilation (9 studies: mean difference − 5.07 days, 95% CI − 7.42 to − 2.73, n = 572, p < 0.0001; I2 = 54%). Parenteral administration was associated with a greater effect on overall mortality than enteral administration (test of subgroup differences, p = 0.04), whereas studies of parenteral subgroups had lower quality. There were no subgroup differences based on baseline vitamin D levels.

Conclusions

Vitamin D supplementation in critically ill patients may reduce mortality. Parenteral administration might be associated with a greater impact on mortality. Heterogeneity and assessed certainty among the studies limits the generalizability of the results.

Trial registration: PROSPERO international prospective database of systematic reviews (CRD42021256939—05 July 2021).
The iHealth-T2D study: a cluster randomised trial for the prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes—a statistical analysis plan
Authors: Muilwijk Mirthe , Loh Marie , Mahmood Sara , Palaniswamy Saranya , Siddiqui Samreen , Silva Wnurinham , Frost Gary S. , Gage Heather M. , Jarvelin Marjo-Riitta , Rannan-Eliya Ravindra P. , Ahmad Sajjad , Jha Sujeet , Kasturiratne Anuradhani , Katulanda Prasad , Khawaja Khadija I. , Kooner Jaspal S. , Wickremasinghe Ananda R. , van Valkengoed Irene G. M. , Chambers John C.
Published: September 2022

Background

South Asians are at high risk of type 2 diabetes (T2D). Lifestyle modification is effective at preventing T2D amongst South Asians, but the approaches to screening and intervention are limited by high costs, poor scalability and thus low impact on T2D burden. An intensive family-based lifestyle modification programme for the prevention of T2D was developed. The aim of the iHealth-T2D trial is to compare the effectiveness of this programme with usual care.

Methods

The iHealth-T2D trial is designed as a cluster randomised controlled trial (RCT) conducted at 120 sites across India, Pakistan, Sri Lanka and the UK. A total of 3682 South Asian men and women with age between 40 and 70 years without T2D but at elevated risk for T2D [defined by central obesity (waist circumference ≥ 95 cm in Sri Lanka or ≥ 100 cm in India, Pakistan and the UK) and/or prediabetes (HbA1c ≥ 6.0%)] were included in the trial. Here, we describe in detail the statistical analysis plan (SAP), which was finalised before outcomes were available to the investigators. The primary outcome will be evaluated after 3 years of follow-up after enrolment to the study and is defined as T2D incidence in the intervention arm compared to usual care. Secondary outcomes are evaluated both after 1 and 3 years of follow-up and include biochemical measurements, anthropometric measurements, behavioural components and treatment compliance.

Discussion

The iHealth-T2D trial will provide evidence of whether an intensive family-based lifestyle modification programme for South Asians who are at high risk for T2D is effective in the prevention of T2D. The data from the trial will be analysed according to this pre-specified SAP.

Ethics and dissemination

The trial was approved by the international review board of each participating study site. Study findings will be disseminated through peer-reviewed publications and in conference presentations.

Trial registration

EudraCT2016–001,350-18. Registered on 14 April 2016. ClinicalTrials.govNCT02949739. Registered on 31 October 2016.
Prevalence of major digestive and respiratory helminths in dogs and cats in France: results of a multicenter study
Authors: Bourgoin Gilles , Callait-Cardinal Marie-Pierre , Bouhsira Emilie , Polack Bruno , Bourdeau Patrick , Roussel Ariza Clarisse , Carassou Lisa , Lienard Emmanuel , Drake Jason
Published: September 2022

Background

The local distribution of helminths in dogs and cats and the evaluation of risk of contamination represent an important challenge for veterinarians due to their effects on animal health and their potential zoonotic risk. The overall goal of this study was to estimate the prevalence of the digestive and respiratory helminths infecting client-owned dogs and cats in France.

Methods

Faecal samples were collected from 414 pet dogs and 425 pet cats at 20 study sites during 2017–2018 and analysed by coproscopy. The samples included specimens collected from animals of both genders and various breeds and ages from a variety of living environments, and with different lifestyles and feeding regimes. Associations between parasitic infection and qualitative factors were explored.

Results

Overall, 125 (14.9%) samples (15.2% in dogs and 14.6% in cats) were positive for at least one of the species of helminths identified. Infection rates were highest forToxocara canisandToxocara cati(8.5% and 11.3%, respectively), whileToxascaris leoninawas found only in one cat (0.2%). The apparent prevalence ofAncylostoma caninumandUncinaria stenocephalain dogs was 1.7% and 4.3%, respectively. No hookworms were found in cats. Whipworms (Trichuris vulpis) were identified in 2.7% of the dogs. Tapeworms (Dipylidium caninumand Taeniidae) were rarely found (< 1% in dogs and < 3% in cats). The prevalence ofAngiostrongylus vasorum Crenosoma vulpis, andStrongyloides stercoralis in dogs,Aelurostrongylus abstrususin cats andEucoleus spp./Capillaria spp.in both dogs and cats was < 1%. Significantly higher fecal parasite emission rates were identified in young individuals, in animals with outdoor access, in animals living in the countryside and in intact animals (especially in cats). In addition, cats not fed exclusively with commercial diets and living with other animals (dogs and/or cats) were at higher risk for parasites. For dogs, hunting/herding and walking off-leash were found to be additional risk factors. Furthermore, pets with no reported history of deworming or dewormed > 1 year before the study were positive for parasites significantly more often than pets dewormed < 1 year before study participation.

Conclusions

The overall prevalence of helminths (some of which are zoonotic), the risk factors and the reportedly low deworming frequencies identified in this study (20.5% animals having never been dewormed and only 26.4% dewormed ≥ 3 times/year) illustrate the need for improving pet owners’ adherence to anthelmintic guidelines in France.

Graphical Abstract
Fungal keratitis caused by Scedosporium apiospermum: a case report
Authors: Erkan Pota Çisil , Ayaz Yusuf , Ünal Mustafa , Koyuncu Özyurt Özlem
Published: September 2022

Background

We present a case of fungal keratitis caused by Scedosporium apiospermum, which is a rare agent.

Case description

A 34-year-old Caucasian male patient was admitted to our clinic with complaints of pain and blurred vision in the left eye. The patient had a history of wearing contact lenses for 3 years. According to the Snellen chart, the patient’s visual acuity was 20/20 and counting fingers at 30 cm, for right and left eyes, respectively. A 3 × 3 mm corneal abscess at the center of the cornea with hypopyon in the patient’s left eye was observed. After the patient was hospitalized, fortified gentamicin and fortified cefazolin drops were started 24 times per day. Intravenous fluconazole 1 × 800 mg loading, 1 × 400 mg maintenance dose, intravenous vancomycin 4 × 500 mg and intravenous cefoperazone + sulbactam 2 × 2 g treatments were started. We observed S. apiospermum in the corneal scraping sample, which the identification was performed by combined phenotypic characteristics and matrix-assisted laser-desorption ionization time-of-flight mass spectrometry on the sixth day of treatment. The drops were revised as fortified vancomycin, ceftazidime, and voriconazole drops 24 times per day. Intravenous voriconazole 2 × 6 mg/kg loading and 2 × 4 mg/kg maintenance dose treatments were started. Three weeks later, left eye visual acuity increased to 20/40, and the corneal abscess regressed. On second-year follow-up, his visual acuity increased to 20/25 for the left eye and the cornea was transparent.

Conclusion

Scedosporium group is an opportunistic filamentous fungus that is very rarely seen and causes severe keratitis infections. In the literature, to the best of our knowledge, three cases of keratitis due to S. apiospermum after contact lenses were reported, and all were treated with penetrating keratoplasty. In this case, unlike the others, only medical treatment was applied. In cases with suspected fungal keratitis, medical treatment should be started without waiting for the culture result, the findings should be followed and penetrating keratoplasty should be performed in the case of no response to treatment.